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Long-Term Treatment of Atopic Dermatitis
Abstract
Many patients with mild to moderate atopic dermatitis (AD) are managed by identifying and avoiding allergens and irritants, ensuring skin moisturization, and graded use of topical corticosteroids and/or calcineurin inhibitors. There is little consensus on the next step. Most systemic therapies are "off label" in the United States and include phototherapy, cyclosporine, mycophenolic acid precursors, azathioprine, and methotrexate. The decision to use these therapies should be based on efficacy and safety readouts from well designed, long-term trials. This article reviews the long-term randomized, controlled trials examining safety and/or efficacy of interventions recommended for patients with mild to severe AD.
... Daily di use application of a well-formulated moisturizer for skin barrier maintenance and the application of prescription topical therapies to persistent AD lesions remain part of the standard therapeutic regimen, especially for localized refractory and licheni ed sites. [1][2][3][4][5][6] Finding the optimal balance of therapeutic choices varies among individual patients and requires careful consideration of the overall clinical situation and speci c patient-related factors, such as age, severity of AD signs and symptoms, and patient and clinician comfort levels with the treatments selected. Ultimately, the clinician should identify what is most likely to achieve an optimal level of control and express their treatment recommendations to the patient with realistic con dence and a proper bene t versus risk discussion. ...
... When patients with moderate-to-severe AD and their clinicians are considering systemic therapy for AD, a variety of treatment options are available. 3,[5][6][7][8][9][10][11][12] Prior to 2018, available systemic therapies for AD were primarily oral agents, such as cyclosporin, methotrexate, azathioprine, and mycophenolate mofetil, all of which appear to modulate the underlying pathophysiologic pathways that contribute to AD. 3,6-8 Each of these agents has variable amounts of data available regarding its use in children and adults for treatment of AD. 3,6-12 However, none of these oral agents are approved by the United States Food and Drug Administration (FDA) for the treatment of AD, and all exhibit immunosuppressant properties. 3,8 Oral antihistamines have also been used as part of the treatment regimen for AD, primarily as an adjunctive therapy to help reduce pruritus and/or decrease interference with sleep (i.e., sedating antihistamines). ...
... 12 It is important to note that chronic or frequent use of systemic CS is best avoided in children and adults due to the risk of several signi cant AEs. 6,[10][11][12] Cyclosporin. Among the conventional systemic oral agents used in the management of AD, cyclosporin appears to exhibit the fastest onset of e cacy, but its use is limited by its safety pro le, which includes risks of nausea, cephalgia, hypertension, nephrotoxicity, sequelae of chronic immunosuppression, gingival hyperplasia, and drug interactions. ...
Atopic dermatitis (AD) is a chronic disorder that requires thorough patient education and a therapeutic management strategy designed to control flares, decrease recurrences, and reduce pruritus. In cases that cannot be controlled by proper skin care and barrier repair, topical therapy, and avoidance of triggers, systemic therapy is often required to control flares and maintain remission. It is important for clinicians to avoid becoming overly dependent on the intermittent use of systemic corticosteroid therapy to control flares, without incorporating other treatment options that might more optimally control AD over time. This article provides an overview of systemic therapies, including conventional oral therapy options and injectable biologic agents, that modulate the immune dysregulation in AD. Major emphasis is placed on the monoclonal antibodies currently available (e.g., dupilumab) for the treatment of AD, as well as those in latter stages of development, with a focus on agents targeting IL-4and/or IL-13.
... Based on seven long-term RCTs, CsA can be recommended as an effective second-line agent for AD for up to 1-2 years in both adults and children 2 years and older. [48] Dosage and scheduling: CsA is applicable to patients 16 years of age or older with failure/resistance to first-line therapies. The drug should be administered twice a day at a daily dose of 3-5 mg/kg/day. ...
... CsA has been shown to be effective and relatively safe in four long-term RCTs in adults who received up to 1 year of continuous treatment. [48] Low starting doses (3 mg/kg/day) and high starting doses (5 mg/ kg/day) were found to be equally effective (EASI/body surface area improvement) after 2 weeks. [49] Adverse effects and monitoring: Irreversible nephrotoxicity, infection, hypertension, electrolyte disturbances, dyslipidemia, tremor, hypertrichosis, headache, gingival hyperplasia, and nonmelanoma skin cancer are the major serious side effects of CsA. ...
Background: Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin
condition that affects all age groups. There was a dearth of consensus document on AD for
Indian practitioners. This article aims to provide an evidence‑based consensus statement for
the management of AD with a special reference to the Indian context. This guideline includes
updated definition, etiological factors, classification, and management of atopic dermatitis.
Methodology: The preparation of guidelines was done in multiple phases. Indian Dermatology
Expert Board Members (DEBM), recommended by the Skin Allergy Society of India, prepared 26
evidence‑based recommendations for AD. An extensive literature search was done in MEDLINE,
Google scholar, Cochrane, and other resources. Articles published in the past 10 years were
reviewed and recommendations were graded based on the quality of evidence as per GRADE.
After forming the initial structure, DEBM met in Mumbai and gave their decisions on an agree
and disagree scale with an Indian perspective. Finally, their suggestions were compiled for
preparing the article. After DEBM finalized the draft, a treatment algorithm was formulated
for the management of AD. Results: DEBM suggested a working definition for AD. The panel
agreed that moisturizers should be used as mainstay of therapy and should be continued in
all lines of therapy and in maintenance phase. Topical corticosteroids and topical calcineurin
inhibitors should be considered as the first line of treatment. Among systemic therapies,
cyclosporin should be considered first line, followed by azathioprine, methotrexate, and
mycophenolate mofetil. Phototherapy can be an effecive alternative. Empirical food restriction
was recommended against. Conclusion: These guidelines should form a reference for the
management of patients with AD in an evidence‑based manner.
... In the treatment of some diseases that need to suppress excessive immune responses, it reduces key cytokines by preventing signal transmission after T-cell activation, which it can effectively control the response of the immune system, prevent skin layer damage and reduce symptoms (Ko et al. 2016). Although cyclosporine A can quickly relieve the symptoms of AD, its long-term use still has certain side effects, such as nephrotoxicity and increased risk of infection, so short-term use is only recommended (Prezzano and Beck 2017). ...
Atopic dermatitis (AD) is a complex chronic inflammatory skin disorder, with its incidence significantly increasing in recent years. The pathogenesis of AD is complex, involving multiple factors such as genetic susceptibility, dysbiosis of the skin microbiome, autoimmune abnormalities, impaired epidermal barrier function, and environmental factors. These factors collectively contribute to the high incidence of the disease and its significant socio-economic burden. This article reviews the pathogenesis of AD and analyzes the current traditional treatment approaches, including topical and systemic therapies, highlighting the issues they face. It focuses on the current status and treatment strategies. Specifically, as the significant heterogeneity of AD, treatment paradigms are gradually shifting from a “one-size-fits-all” approach to personalized treatments. The aim is to achieve more effective management of AD and address the issues arising from individual differences. Through these discussions, this article aims to provide new perspectives and strategies for the clinical treatment of AD, in order to reduce the disease burden on patients.
... Este medicamento está aprobado en algunos países europeos y en Colombia y está recomendado condicionalmente en las guías estadounidenses (6,9) . Su no uso puede deberse a temor de los efectos secundarios, como nefrotoxicidad irreversible, hipertensión arterial y cáncer de piel no melanoma (14) . ...
Introducción: la dermatitis atópica es una enfermedad inmunomediada cada vez más estudiada. El objetivo de este estudio es identificar los criterios diagnósticos, las escalas de clinimetría, los tratamientos de preferencia. Además, las causas de elección y cambio de terapia y el tiempo de espera para ver la respuesta terapéutica. Metodología: es un estudio observacional, descriptivo de corte transversal. Se hizo por medio de una encuesta virtual distribuida durante actividades académicas, previa realización de prueba piloto. Resultados: se encuestaron 68 dermatólogos, el 29.3% basa el diagnóstico según la clínica, seguido de los criterios de Hanifin y Rajka (23.08%). Las escalas clínimétricas más usadas son DLQI, EASI, y valoración clínica (29.85%). La primera línea terapéutica para la enfermedad leve son corticoesteroides de mediana potencia (52.31%). En segunda línea prefieren cambio de potencia del corticoesteroide (38.46%). Las principales causas de iniciar terapia sistémica son: 1. la clínica severa y 2. alteración severa de la calidad de vida. Para elegir terapia sistémica se tiene en cuenta la severidad clínica y la eficacia del medicamento según literatura. En la DA moderada-severa la primera opción es fototerapia (59.38%) y corticoesteroides sistémicos (25%). Como segunda opción ciclosporina (25%), fototerapia (18.75%), azatioprina (18.75%). Conclusiones: es el primer estudio en Latinoamérica al respecto. Se encontró que no hay consenso sobre el diagnóstico y manejo de la enfermedad. En algunos casos no se está esperando el tiempo necesario para ver una respuesta clínica. Aporta información única sobre el tratamiento de dermatitis atópica y sugiere realizar actividades académicas para unificar conceptos entre especialistas.
... The AAAAI/ACAAI Joint Task Force (2023) conditionally recommends CsA in patients with moderate to severe AD who are refractory, intolerant or unable to use mid to high potency topical treatment and systemic treatment inclusive of biologics [14]. CsA is approved in Europe, Australia and Japan for the treatment of AD in patients aged 16 years and above [46]. European guideline (EuroGuiDerm) on atopic eczema recommends CsA to achieve disease control in AD patients who are candidates for systemic treatment in the following doses [26]: a) Adults: 2.5-5 mg/kg/day in two divided doses ...
Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.
... Another study also shows significantly prolonged drug survival and post-drug survival for MTX in comparison to cyclosporine (31). MTX, however, does come with a risk of severe side effects, including gastrointestinal disorders, pulmonary fibrosis, and hepatotoxicity (32,33). Folic acid is often administered to mitigate these side effects (5,6). ...
Background:
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.
Materials and methods:
A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.
Results:
Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5–15 mg/week and 14.5–25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5–15 mg/week for adults and 10–15 mg/m²/week for children. Maintenance doses suggested were 7.5–25 mg/week for adults and 0.2–0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.
Conclusion:
This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
... Corticosteroids, the most common medications prescribed for atopic dermatitis, offer limited efficacy or short-lived symptomatic relief. Many patients initially responsive to corticosteroids often encounter adverse drug effects or develop treatment resistance over time (50). Biologics that block the action of cytokines driving allergic inflammation are more potent and less toxic than corticosteroids and other conventional medications but provide clinical benefit only in subsets of patients and often fail to achieve durable remission (5153). ...
Keratinocytes, the epithelial cells of the skin, reprogram their gene expression and produce immune effector molecules when exposed to environmental and endogenous triggers of inflammation. It remains unclear how keratinocytes process physiological signals generated during skin irritation and switch from a homeostatic to an inflammatory state. In this article, we show that the stress-activated protein kinase p38α is crucial for keratinocytes to prompt changes in their transcriptome upon cytokine stimulation and drive inflammation in allergen-exposed skin. p38α serves this function by phosphorylating p63, a transcription factor essential for the lineage identity and stemness of the skin epithelium. Phosphorylation by p38α alters the activity of p63 and redeploys this developmental transcription factor to a gene expression program linked to inflammation. Genetic ablation and pharmacological inhibition of p38α or the p38α-p63 target gene product MMP13 attenuate atopic dermatitis-like disease in mice. Our study reveals an epithelial molecular pathway promoting skin inflammation and actionable through treatment with topical small-molecule therapeutics.
... While the pathogenesis is currently under discussion, several researchers have documented the major role of defective epidermal barrier function in inducing disease, with marked epidermal hyperplasia and Th2 and Th22 immune activation that can progress to Th1 in chronic stages. Over the past three decades, the incidence of atopic dermatitis in developed countries has tripled (Ortiz-Salvador, 2017;Patrizi, 2015;Prezzano, 2017;Rodenbeck, 2016;Fernández-Guarino, 2016). ...
This is the next book in the scientific book series entitled "Advances in biomedical
research". This book series is the result of the meetings and work of scientists from
various universities and institutes in Poland. In this monograph we present the topics in
Biomedical Research from 2021. All presented articles have passed the peer-review
process positively. The articles come from various fields of biomedicine from Cell-inCell phenomena throughout cancer research to skin disorders. Wishing you enjoyable
and productive reading. Editors, L.Bialy, I Mlynarczuk-Bialy https://bc.wydawnictwo-tygiel.pl/publikacja/4D2E20CF-4ADE-0211-0229-3237E8326A1A
... Anti-inflammatory treatment may also be necessary (37). The decision to use these therapies should be based on efficacy and safety readouts from well designed, long-term trials (38). ...
Background:
Atopic eczema is the most common type of skin disorder in both children and adults. It is characterized by erythema, pruritus, papules, xeransis, and lichenification. Qinzhuliangxue decoction (QZLXD), a Chinese herbal medicine (CHM) prepared with several ingredients that are used to treat eczema, was formulated according to the traditional Chinese medicine (TCM) theory. This study aimed to investigate the efficacy and safety of QZLXD administration for treating atopic eczema compared to those of Runzaozhiyang capsules (RZZYC).
Methods:
A total of 176 patients were enrolled at the Shanghai Yueyang Hospital and were randomly assigned to the QZLXD treatment group (n=82) or the RZZYC control group (n=86). The differences in Eczema Area and Severity Index (EASI), Dermatology Life Quality Index, itching score, recurrence rate, and adverse events (AEs) were compared between the groups.
Results:
The EASI score (x2=14.181, P=0.003), recurrence rate (x2=7.398, P=0.007), and itching score (F=-3.427, P=0.001) were lower in the QZLXD group than in the RZZYC group. Incidence of AEs was similar between the RZZYC and QZLXD groups (P=0.434).
Conclusions:
QZLXD is recommended for the treatment of subacute atopic eczema because QZLXD showed good efficiency with low recurrence rate and tolerable AEs.
... UVA1 phototherapy in monotherapy has emerged as a highly effective and well-tolerated treatment in a variety of inflammatory disorders including atopic dermatitis. [29][30][31] UVA1 in monotherapy was initially administered to patients with AD according to a high dose regimen but during the last years, numerous trials confirmed that not only high dose but also medium dose UVA1 induces significant improvement in adult patients with acute exacerbations of AD and that high/medium dosage are both more effective than UVA/UVB or low dose UVA1 treatment. 32 Concerns towards long term side effects associated with massive UVA1 dosages, led many photodermatologists to use a medium dose protocol. ...
... UVA1 phototherapy in monotherapy has emerged as a highly effective and well-tolerated treatment in a variety of inflammatory disorders including AD. [28][29][30] UVA1 in monotherapy was initially administered to patients with AD according to a high dose regimen but during the last years, numerous trials confirmed that not only high dose but also medium dose UVA1 induces significant improvement in adult patients with acute exacerbations of AD and that high/ medium dosage are both more effective than UVA/UVB or low dose UVA1 treatment. 31 Concerns towards long term side effects associated with massive UVA1 dosages, led many photodermatologists to use a medium dose protocol. ...
Background
The current evidences attest UVA1 phototherapy as effective in the treatment of severe atopic dermatitis (AD). Furthermore, in this indication, ‘medium dose’ is as effective as ‘high dose’ regimen. To date, a randomized comparison study evaluating the effectiveness as well as safety of different UVA1 protocols in different skin types in the treatment of adult patients with severe AD is still lacking.
Objective
The aim of the present study was to compare the safety and the efficacy of medium and high dose UVA1 either in fair or in dark skin types.
Methods
Twenty‐seven adult patients with severe AD were consecutively included in a randomized, controlled, open, two arms trial Severity of AD was determined by means of SCORAD index and clinical improvement was also monitored. A total of 13 out of 27 patients were treated with high dose (130 J/cm²) UVA1 protocol while 14 out of 27 patients received medium dose (60 J/cm²) UVA1 protocol. Phototherapy was performed five times weekly up to 3 weeks. Before and after UVA1 treatment each patient was evaluated for skin pigmentation through Melanin Index (MI) quantitative evaluation.
Results
Skin status improved in all patients resulting in a reduction of SCORAD index in all groups. Our results demonstrated that among patients with darker skin types and higher MI, high dose UVA1 was significantly more effective than medium dose (P < 0.0001) while within the groups with skin type II, no significant differences between high and medium dose protocols were observed.
Conclusion
Our study, confirms previous observations that UVA1 phototherapy should be considered among the first approaches in the treatment of patients with severe generalized AD and also demonstrates that in darker skin types, high dose UVA1 phototherapy is more effective than medium dose in the treatment of adult patients with severe AD.
... Topical corticosteroids are considered the first-line therapy for AD. 4,5 However, their long-term use can be associated with relevant side effects and patients may be reluctant to continue this therapy given the risk of adverse events, ultimately contributing to treatment failure. [6][7][8] Two topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD. 7 Whilst they are both inhibitors of calcineurin, tacrolimus and pimecrolimus have distinct pharmacological and efficacy profiles. ...
Background
Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment.
Objective
Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus.
Methods
Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July–September 2017) and a face‐to‐face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta‐analysis, clinical trials or large observational studies were also discussed based on clinical experience.
Results
In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns.
Conclusion
Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.
Off-label treatment is the use of a drug approved for marketing, outside the registration in terms of indication, age group, dose or route of administration. Despite the constant appearance of new preparations on the market, treatment outside the SmPCs guidelines is a current clinical problem. It is believed that it is based on the needs of patients unmet by classical therapy methods. This work focuses on off-label treatment in inflammatory dermatoses such as atopic dermatitis, psoriasis, acne vulgaris and rosacea. Publications on this subject, available on PubMed, Google Scholar and the Cochrane Library, were analyzed in the form of a review, taking into account the mechanisms of action, efficacy and safety of preparations. Based on the literature analysis, it can be concluded that the use of drugs outside the SmPC indications is a common situation in dermatology. However, it is difficult to determine its exact frequency—there is a lack of data on the prevalence of off-label appliances in inflammatory dermatoses from a European perspective. Publications demonstrate varying effectiveness and safety of this form of therapy, depending on the specific preparation. Off-label treatment in dermatology remains an important and current clinical issue that should be explored in further research.
Atopic dermatitis (AD) is a common, genetically influenced, inflammatory skin disorder affecting children, adolescents, and adults, is markedly pruritic, and has a complex pathophysiology. The disease course is prolonged, characterized by periods of marked flaring that are separated by periods of relative remission. More recent advances in understanding the pathophysiology of AD have led to more targeted therapies, especially injectable monoclonal antibodies and Janus kinase inhibitors, although many compounds continue to be studied that are associated with a wide variety of suggested modes of action. This chapter walks the reader through the thought process regarding management of chronic and persistent atopic dermatitis. The chapter also addresses the pipeline of potential new agents, advances in understanding phenotypes and endotypes of AD, biomarkers that may assist in management and/or optimize treatment selection, and the progressive development of personalized medicine.
Atopic dermatitis (AD) is characterized by a heterogenous longitudinal course with varying severity, flares, and persistence. However, AD course is not routinely assessed in clinical practice or controlled trials. Our objective was to review the longitudinal course of AD in children and adults and discuss implications for routine practice and clinical trials. We conducted a focused review of the published literature, including retrospective, prospective, and interventional studies, clinical trials, and consensus guidelines. Estimates of AD persistence varied widely across studies but suggested that AD can indeed persist through childhood and into adulthood. Predictors of persistence are broad and include both disease-intrinsic and disease-extrinsic (i.e., environmental) factors. In real-world practice, most individuals with AD experience fluctuations in the signs and symptoms over time and do not experience persistent clearance of skin lesions. Clinical trials use mainly static measurements that do not take into account fluctuations in course, which may confound treatment effects. The heterogenous temporal pattern of AD can be incorporated into routine practice to better set expectations and offer a realistic prognosis. AD course should be routinely incorporated into clinical decision making. Future studies are needed to develop a standardized approach to AD assessment and treatment that includes longitudinal course.
Atopic dermatitis is a complex disease process requiring a multifactorial approach in managing baseline disease, responding appropriately to flares, and optimizing preventative measures. This chapter reviews the role of bathing practices, topical anti-inflammatories, and topical antimicrobials in such management. Bathing practices, including frequency, duration, use of additives, and choice in cleansers/soaps, can improve or worsen the epithelial barrier. Although data are mixed and recommendations vary by organization and region, we recommend daily bathing in lukewarm water for less than ten minutes using neutral to mildly acidic non-soap cleansers, followed by the immediate application of emollients. Topical anti-inflammatories include topical corticosteroids, topical calcineurin inhibitors, and phosphodiesterase-4 inhibitors. Topical corticosteroids are the standard therapy for acute flares and patients who have failed conservative management with emollient alone. Providers must be astute in their utilization and optimize dosing, application vehicle, frequency, duration, and body location, to maximize benefit while minimizing potential side effects. Topical calcineurin inhibitors represent a steroid-sparing alternative that can be used for patients who require application to sensitive areas such as the face, eyelids, or genitalia, or who have developed side effects from or failure to respond to topical corticosteroids. Phosphodiesterase-4 inhibitors are a newer steroid-sparing alternative also to be considered. Topical antimicrobial methods include judicious utilization of topical antibiotics and the use of dilute bleach baths for prevention/decolonization. The data on the benefit of such methods are mixed, but they can be considered adjunctive therapy in those patients with frequent disease flares.
Background
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with heterogeneous morphology and distribution, symptoms, severity, extent, longitudinal course, quality-of-life burden, comorbidities, and treatment response. This heterogeneity contributes to challenges in diagnosis, characterization of disease activity, and therapeutic stratification.
Objective
To develop a framework to standardize AD assessment.
Methods
We propose a novel framework to assess AD based on literature review and clinical experience.
Results
DESCRIBE-AD is a framework that can effectively capture the clinical domains contributing to AD heterogeneity and includes both patient- and clinician-reported perspectives. DESCRIBE-AD includes assessments of Dermatitis morphology and phenotype, Evolution of disease, Symptom severity, Comorbid health disorders, Response to therapy, Intensity of lesions, Burden of disease, and Extent of lesions. Rather than placing focus on any single specific aspect of AD, DESCRIBE-AD allows for a comprehensive approach to the assessment and clinical management of AD.
Conclusion
DESCRIBE-AD is a novel framework that can be used to better describe the heterogeneity of AD and guide treatment decisions.
Topical drugs are a basic treatment used by the majority of patients with mild-to-severe atopic dermatitis. Topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs) are, clinically, the most widely used representative topical drugs. In recent years, non-steroidal anti-inflammatory drugs with various mechanisms have been developed and are being tested as new therapeutic agents. In addition, since moisturizers for therapeutic purposes are applied in practice with topical corticosteroid and topical calcineurin inhibitor, moisturizers, and baths for basic skin care are crucial when expanding the scope of topical preparations.
Background
Atopic dermatitis (AD) patients have heterogeneous clinical phenotypes, including different combinations of itch and lesional severity. Little is known about the characteristics and course of these subtypes.
Objective
To determine the characteristics, associations, burden, and course of AD patients using combined itch and lesional severity.
Methods
A prospective practice-based study was performed using questionnaires and physical examination (n=592). AD subsets were defined using verbal rating scale for average-itch combined with either EASI, objective- SCORAD or vIGA-AD as follows: mild-moderate itch and lesions (MI/ML), mild-moderate itch and severe lesions (MI/SL), severe itch and mild-moderate lesions (SI/ML), severe itch and lesions (SI/SL).
Results
At baseline, there were only weak-moderate correlations of numerical rating scales for worst-itch or average-itch, or SCORAD-itch with EASI, objective-SCORAD, body surface area, and vIGA-AD (Spearman's rho=0.32-0.62). Most patients had MI/ML (59.4-62.3%), followed by SI/ML (21.3%-29.1%), SI/SL (6.0%-12.9%), and MI/SL (3.8%-6.4%). Patients with SI/SL, followed by SI/ML and MI/SL, described their AD as being more severe overall and had worse impairment in sleep, mental health, and quality of life. However, those with MI/SL or SI/SL were far more likely to be classified as severe by a physician (multivariable logistic and linear regression, P<0.005 for all). Baseline MI/SL, SI/ML and SI/SL were associated with similar longitudinal courses over time, and more AD flares and itch-triggers than MI/ML.
Conclusion
Combined itch and lesional severity appear to describe unique AD phenotypes. Further studies are needed to confirm these findings and understand the optimal treatments for these groups.
Résumé
La dermatite atopique peut avoir un retentissement très important chez les enfants et les adolescents. Avoir des lésions visibles mais surtout un prurit quasi-permanent ou parfois une douleur cutanée a forcément des conséquences sur tous les aspects de la vie quotidienne, dont le sommeil, sur la scolarité et sur les relations avec les autres, la vie familiale et affective. Il y a aussi un retentissement dans toute la famille. Mal connue, la stigmatisation peut être réelle. Les traitements et surtout les soins locaux peuvent être très astreignants. L’adhésion au traitement est donc souvent difficile. La qualité de vie peut être fortement altérée et la dermatite atopique représenter un lourd fardeau. Les conséquences psychologiques peuvent être majeures. Des problématiques familiales liées à la maladie s’installent souvent. Le meilleur moyen d’en sortir est probablement de disposer de traitements très efficaces et bien tolérés.
© 2020 Elsevier Masson SAS. Tous droits réservés.
Background
Little is known about the longitudinal course of adult atopic dermatitis (AD) lesional severity and extent in clinical practice.
Objective
To determine the longitudinal course of AD in clinical practice.
Methods
A prospective, dermatology practice-based study was performed (n=400). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months by Eczema Area and Severity Index (EASI) and objective Scoring Atopic Dermatitis (objective-SCORAD). Multivariable repeated-measures linear regression models were constructed to examine AD severity over time.
Results
Overall, 36.2% and 18.2% of patients had moderate (6.0-22.9) or severe (23.0-72.0) EASI scores at any visit, respectively. Similarly, 29.0% and 26.4% of patients had moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores at any visit, respectively. Among patients with baseline moderate (6.0-22.9) or severe (23.0-72.0) EASI scores, 25.0% and 18.6% continued to have moderate or severe scores at ≥1 follow-up visits, respectively. Similarly, among patients with baseline moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores, 22.6% and 24.5% continued to have moderate or severe scores at ≥1 follow-up visits, respectively. In longitudinal regression models, EASI was significantly associated with BSA (adjusted beta [95% confidence interval]: 0.16 [0.09-0.23]) and edema/papulation (2.31 [0.19-4.43]). Objective-SCORAD was significantly associated with BSA (0.12 [0.04-0.21]), edema/papulation (4.69 [2.05-7.32]) and scratch (3.34 [0.45-6.24]) over time.
Conclusion
AD lesional severity has a heterogeneous longitudinal course. Many patients had fluctuating lesional severity scores over time. A minority of patients had persistently moderate or severe lesions over time. Most patients with moderate-severe disease at baseline were unable to achieve persistent lesional clearance.
Introduction: The prevalence of atopic dermatitis (AD) in geriatric populations of industrialized countries is currently estimated at 3-4% and continues to increase. AD is associated with significant morbidity, increased susceptibility to infection, and symptoms of pruritus and pain. Treatments may negatively affect elderly patients; thus, plans should be optimized for this population.
Areas covered: This review summarizes treatment options for AD in the elderly. A systematic review of the literature was conducted using the key terms atopic dermatitis, elderly, geriatric, systemic therapy, therapy, and topical therapy in PubMed. Searches yielded articles on skincare management and topical and systemic pharmacotherapies.
Expert opinion: Proper use of moisturizer is crucial in all patients with AD. Topical corticosteroids are commonly prescribed; however, they carry an increased risk of adverse events such as skin atrophy. Systemic corticosteroids should be avoided in elderly patients due to questionable efficacy and increased adverse events. Topical calcineurin inhibitors and crisaborole are similarly efficacious with an excellent safety profile. Cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil are systemic agents available for the treatment of refractory AD; however, insufficient data exist to indicate the superiority of any one agent. Dupilumab is a safe and efficacious injectable therapy in elderly patients.
In this study, beclomethasone dipropionate nanocrystals were formulated using an antisolvent sonoprecipitation technique. The aim of this study was to assess the ability of these nanocrystals to actively accumulate in skin layers for the treatment of atopic dermatitis with minimal systemic levels. A three-factor, three-level central composite design was employed to optimize the formulation parameters. The following formulation variables were adopted: stabilizer concentration, antisolvent volume, and stabilizer type. The nanocrystals were assessed for particle size, zeta potential and polydispersity index. Saturation solubility and ex vivo studies were carried out on the optimized formula (PN1). The saturation solubility of PN1 was approximately 745.5 times that of raw BDP in water. Ex vivo studies showed that the calculated Local Accumulation Efficiency (LAC) in the case of PN1 was 6.20, which was significantly higher (p < 0.05) than that of the brand formula, with a LAC ratio of 0.25. Our results confirmed the enhancement of drug deposition, ascertaining the successful use of nanocrystals for the topical delivery of poorly soluble drugs.
Background:
Previous studies found that childhood atopic dermatitis (AD) and asthma are associated with residence in urban areas. However, little is known about the prevalence and determinants of AD in US urban populations and its impact on quality-of-life (QOL) and asthma.
Objective:
To determine AD prevalence and persistence, sociodemographic predictors thereof, and association with QOL and atopic comorbidities in US urban children.
Methods:
We analyzed data from The Fragile Families and Child Wellbeing Study, a prospective cohort study of 4898 women and their children born in 20 large US cities between 1998 and 2000. AD prevalence was determined at ages 5, 9, and 15 years, and stratified by sex, race/ethnicity, and household poverty income level.
Results:
The prevalences (95% confidence interval [CI]) of childhood AD were 15.0% (11.0%-18.9%), 15.1% (11.5%-18.7%), and 14.5% (10.4%%-18.5%) at ages 5, 9, and 15 years, respectively. Female sex (multivariable repeated measures logistic regression; adjusted odds-ratio [95% CI]: 1.56 [1.02-2.37]) and black race (1.80 [1.07-3.01]) were associated with persistent AD across all 3 ages. Children with AD at ages 5 and 15 (2.63 [1.42-4.86]), 5, 8 and 15 (1.47 [1.02-2.12]) and 9 and 15 years (1.61 [1.00-2.60]) had higher odds of poor/fair/good overall health. Children with AD at ages 5 and 9 years had the highest odds of ever having asthma (adjusted odds ratio [95% confidence interval]: 6.05 [5.88-6.22]), followed by children with AD at ages 5, 9, and 15 years (3.17 [3.07%-3.27]).
Conclusion:
Atopic dermatitis prevalence and persistence were highest in US urban children who were female or black. Urban children with persistent AD were more likely to have poor QOL and asthma.
Background:
Patients with severe atopic dermatitis (AD) may require potent immunosuppressive therapy to control their disease. Mycophenolate mofetil (MMF) has been suggested as a safe and effective drug in these cases.
Objectives:
To investigate effectiveness and tolerability of oral MMF in adult patients with severe recalcitrant AD.
Methods:
During the years 2010-2017 oral MMF 2-3 g/day was administered to adult patients with severe recalcitrant AD who failed other major systemic drugs, or where other drugs, including cyclosporine (CSA), methotrexate, and azathioprine, were contraindicated.
Results:
Of 9 consecutive adult patients, 4 (44%) responded completely, 2 (22%) had partial response, and 3 (33%) did not respond at all. The MMF therapy was continued for 5-36 months (average 21 months) without major side effects.
Conclusions:
Oral MMF may be an effective drug in AD. Due to its good safety profile, it may be recommended as a first-line systemic therapy, or successive to CSA in the long term.
The calcineurin inhibitors (CNIs) belong to a group of immunosuppressive agents that block T-cell activation through the suppression of the calcium/calcimodulin-dependent phosphatase calcineurin. Agents such as cyclosporine A (CSA) and tacrolimus (TAC) have long been used in patients with systemic lupus erythematosus (SLE). TAC is preferred to CSA in SLE because of the lower frequency of cosmetic, hypertensive and dyslipidemic adverse effects. Recent randomised controlled trials have demonstrated noninferiority of TAC to mycophenolate mofetil (MMF) or cyclophosphamide (CYC) for induction therapy of lupus nephritis. Low-dose combination of TAC and MMF has also been shown to outperform CYC pulses in inducing remission of lupus nephritis in Chinese patients. TAC does not affect fertility and is relatively safe in pregnancy. In SLE patients who are intolerant or refractory to conventional immunosuppressives, or where contraindications to other immunosuppressive agents exist, TAC is an alternative option. However, the therapeutic window of TAC is narrow, and drug level monitoring is required to ensure drug exposure and minimise toxicities. Current evidence of TAC in lupus nephritis is limited to 6 months, and its long-term safety as maintenance therapy of SLE is yet to be determined. Newer chemical analogues of CNIs, such as voclosporin, with less variable plasma concentration are being tested in lupus nephritis.
Background:
Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks.
Objective:
We sought to assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766; AD-302: NCT02118792).
Methods:
Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus.
Results:
More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity.
Limitations:
Short study duration was a limitation.
Conclusions:
Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
Background
Many clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical corticosteroids (TCS) have been widely used for >5 decades. Long-term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects. Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, available for 1–2 decades, are not associated with atrophy or increased percutaneous absorption after prolonged use and have much lower potential for systemic effects. However, since 2006 TCIs have carried a controversial Boxed Warning based on a theoretical risk of malignancy (eg, skin and lymphoma) that has limited TCI use for standard-of-care maintenance therapy.
Methods
A comparative systematic search of PubMed was done for long-term (≥12 week) clinical trials of TCS or TCI treatment in patients <12 years with AD. Citations were reviewed for inclusion based on MeSH terms, abstracts, and relevant article text. Studies were excluded if they did not encompass subjects <12 years, or were <12 weeks’ duration, retrospective, meta-analyses, or limited to anecdotal case reports.
Results
Of 27 trials meeting criteria, 21 included 5825 pediatric patients treated with TCIs, and 6 included 1999 patients treated with TCS. TCS studies were limited to low- to mid-potency products, and all but one study lacked a vehicle control. Eight TCI studies were vehicle-controlled, and safety data were well reported, with ≤5 % of patients reporting discontinuation due to adverse effects (DAEs). Cutaneous and systemic adverse events (AEs) were similar in TCI and vehicle groups, with no reports of lymphoma. Safety data in TCS trials were less well reported. DAE incidence was addressed in just 2 trials, and systemic and cutaneous AEs were mostly unreported.
Conclusions
Data supporting long-term use of TCIs are robust, documenting safety and efficacy, while data supporting long-term TCS use are limited to low- to mid-potency products. Our review identifies a lack of information on the safety of commonly prescribed, long-term monotherapy with mid- to high-potency TCS in pediatric AD, and supports standard-of-care maintenance therapy with TCIs and intermittent use of low- to mid-potency TCS for flares.
Atopic dermatitis (AD) is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB)-UVB, broadband (BB)-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB), full-spectrum light (including UVA, infrared and visible light), saltwater bath plus UVB (balneophototherapy), Goeckerman therapy (coal tar plus UVB radiation), psoralen plus UVA (PUVA), and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms) in AD has been established in adults and children, as well as for acute (UVA1) and chronic (NB-UVB) cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed; this technique is recommended with strength C and level of evidence III. Phototherapy is generally considered to be safe and well tolerated, with a low but established percentage of short-term and long-term adverse effects, with the most common being photodamage, xerosis, erythema, actinic keratosis, sunburn, and tenderness. A carcinogenic risk related to UV radiation has not been excluded. Phototherapy also has some limitations related to costs, availability, and patient compliance. In conclusion, phototherapy is an optimal second-line treatment for AD. It can be used as monotherapy or in combination with systemic drugs, in particular corticosteroids. It must be performed conscientiously, especially in children, and must take into account the patient’s features and overall condition.
Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs.
A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear).
Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity.
Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.
Copyright © 2015 by the American Academy of Pediatrics.
Atopic dermatitis (AD) affects adults and children and has a negative impact on quality of life. The present multicentre randomized double-blind controlled trial showed a barrier-improving cream (5% urea) to be superior to a reference cream in preventing eczema relapse in patients with AD (hazard ratio 0.634, p = 0.011). The risk of eczema relapse was reduced by 37% (95% confidence interval (95% CI) 10-55%). Median time to relapse in the test cream group and in the reference cream group was 22 days and 15 days, respectively (p = 0.013). At 6 months 26% of the patients in the test cream group were still eczema free, compared with 10% in the reference cream group. Thus, the barrier-improving cream significantly prolonged the eczema-free time compared with the reference cream and decreased the risk of eczema relapse. The test cream was well tolerated in patients with AD.
Severe atopic dermatitis (AD) is a recurrent and debilitating disease often requiring systemic immunosuppressive treatment. The efficacy of cyclosporine A (CsA) is well proven but potential side effects are concerning. Several reports point at extracorporeal photopheresis (ECP) as an alternative treatment modality with few and mild side effects. However, no direct comparison between CsA and ECP in the treatment of AD has been performed so far.
To compare the efficacy of CsA (3 mg/kg/day) and ECP (administered two consecutive days twice a month) in a cohort of patients with severe AD.
A randomized cross-over study involving twenty patients with severe AD (SCORAD index 41-89) refractory to other treatments. The patients were allocated to a 4-month course of either of the two treatment modalities. Individual relapse periods (2-8 weeks) were interspersed before cross-over to the other treatment modality. Treatment efficacy was evaluated by SCORAD, PRURITUS (VAS-index 0-10), "overall global assessment" and serological biomarkers; sIL-2Rα, sE-selectin, eosinophilocytes, basophilocytes, and sIgE.
15 patients completed treatment. Both treatments lead to a marked and significant decrease in SCORAD and pruritus index. The average reduction of the SCORAD and pruritus index, respectively was a little higher for ECP treatment compared to CsA treatment; however, the differences did not reach statistical significance. The "overall global assessment" was significantly better in patients who underwent ECP therapy as compared to CsA treatment. None of the biomarkers showed significant changes after either treatment when compared to the initial values.
ECP administered on two consecutive days twice a month to patients with severe AD has similar potency as CsA administered daily in a moderate dose. ECP is a treatment alternative in patients with severe AD that do not tolerate or are refractory to conventional immunosuppressants.
Core outcome sets (COSs) are consensus-derived minimum sets of outcomes to be assessed in a specific situation. COSs are being increasingly developed to limit outcome-reporting bias, allow comparisons across trials, and strengthen clinical decision making. Despite the increasing interest in outcomes research, methods to develop COSs have not yet been standardized. The aim of this paper is to present the Harmonizing Outcomes Measures for Eczema (HOME) roadmap for the development and implementation of COSs, which was developed on the basis of our experience in the standardization of outcome measurements for atopic eczema. Following the establishment of a panel representing all relevant stakeholders and a research team experienced in outcomes research, the scope and setting of the core set should be defined. The next steps are the definition of a core set of outcome domains such as symptoms or quality of life, followed by the identification or development and validation of appropriate outcome measurement instruments to measure these core domains. Finally, the consented COS needs to be disseminated, implemented, and reviewed. We believe that the HOME roadmap is a useful methodological framework to develop COSs in dermatology, with the ultimate goal of better decision making and promoting patient-centered health care.Journal of Investigative Dermatology advance online publication, 4 September 2014; (2014) 0, 000-000. doi:10.1038/jid.2014.320.
A one-year, randomized, double-blind study was conducted in 80 patients with atopic dermatitis treated with tacrolimus ointment or a corticosteroid regimen (hydrocortisone acetate 1% ointment for head and neck, hydrocortisone butyrate 0.1% ointment for trunk and limbs) to compare efficacy and safety, and effects on Th2-reactivity. The study was completed by 36/40 patients in the tacrolimus group, and 31/40 patients in the corticosteroid group. In both groups affected body surface area, eczema area and severity index, and transepidermal water loss decreased at months 6 and 12. Tacrolimus was superior for all efficacy scores at month 6, and in the head and neck area at month 12. Recall antigen reactivity increased at month 12 in both groups. Adverse events were reported by 40/40 patients in the tacrolimus, and by 34/40 patients in the corticosteroid group. Long-term treatment with topical tacrolimus or a corticosteroid regimen improves atopic dermatitis and recall antigen reactivity, suggesting an improvement in the Th1/Th2-balance.
The goals were to determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus colonization in patients with atopic dermatitis and to determine whether suppression of S aureus growth with sodium hypochlorite (bleach) baths and intranasal mupirocin treatment improves eczema severity.
A randomized, investigator-blinded, placebo-controlled study was conducted with 31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections. All patients received orally administered cephalexin for 14 days and were assigned randomly to receive intranasal mupirocin ointment treatment and sodium hypochlorite (bleach) baths (treatment arm) or intranasal petrolatum ointment treatment and plain water baths (placebo arm) for 3 months. The primary outcome measure was the Eczema Area and Severity Index score.
The prevalence of community-acquired methicillin-resistant S aureus in our study (7.4% of our S aureus-positive skin cultures and 4% of our S aureus-positive nasal cultures) was much lower than that in the general population with cultures at Children's Memorial Hospital (75%-85%). Patients in the group that received both the dilute bleach baths and intranasal mupirocin treatment showed significantly greater mean reductions from baseline in Eczema Area and Severity Index scores, compared with the placebo group, at the 1-month and 3-month visits. The mean Eczema Area and Severity Index scores for the head and neck did not decrease for patients in the treatment group, whereas scores for other body sites (submerged in the dilute bleach baths) decreased at 1 and 3 months, in comparison with placebo-treated patients.
Chronic use of dilute bleach baths with intermittent intranasal application of mupirocin ointment decreased the clinical severity of atopic dermatitis in patients with clinical signs of secondary bacterial infections. Patients with atopic dermatitis do not seem to have increased susceptibility to infection or colonization with resistant strains of S aureus.
Long-term, safe and effective therapeutic options for managing the chronic relapsing nature of atopic dermatitis are essential for improving patient quality of life. To minimize the risks of continued topical corticosteroid usage and potentially reduce the incidence of flares, we tested the efficacy and safety of a rotational paradigm of initial brief application of topical corticosteroid followed by long-term intermittent application of non-steroidal tacrolimus ointment to previously inflamed sites of dermatitis.
In this 2-phase study, patients who were 2 to 15 years of age and had moderate to severe atopic dermatitis were randomly assigned to 4 days of twice-daily double-blind therapy with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (Phase I acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (Phase I short-term). Patients whose disease stabilized underwent new randomization to double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week to clinically normal-appearing skin for up to 40 weeks (Phase II). Corticosteroid use was prohibited.
Of 206 randomly assigned patients, 152 completed Phase I; 105 of 152 were randomly assigned into Phase II (68 tacrolimus ointment and 37 vehicle). There were no differences in adverse events between alclometasone and tacrolimus (Phase I) or between tacrolimus and vehicle (Phase II). In the acute period, alclometasone-treated patients showed greater improvement in atopic dermatitis signs and symptoms; thereafter, when all patients applied tacrolimus ointment (short-term), there were no differences. In Phase II, tacrolimus-treated patients had significantly more disease-free days compared with vehicle, significantly longer time to first relapse, and significantly fewer disease relapse days.
For patients with stabilized moderate to severe atopic dermatitis, long-term intermittent application of tacrolimus ointment to normal-appearing but previously affected skin was significantly more effective than vehicle at maintaining disease stabilization, with a safety profile similar to vehicle.
To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema.
Randomised, double blind, parallel group study of 18 weeks' duration.
13 general practices and a teaching hospital in the Nottingham area.
174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. Interventions: 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days.
Primary outcomes were total number of scratch-free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm.
No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval -2.0 to 4.0, P=0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline.
A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.
Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.
Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.
BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.
Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).
There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.
Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.
BACKGROUND
Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhib- its signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be impor- tant drivers of atopic or allergic diseases such as atopic dermatitis.
METHODS
In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline at week 16.
RESULTS
We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received du- pilumab every other week and in 87 (36%) who received dupilumab weekly, as com- pared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who re- ceived each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups.
CONCLUSIONS
In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effec- tiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceu- ticals; SOLO 1 ClinicalTrials.gov number, NCT02277743; SOLO 2 ClinicalTrials .gov number, NCT02277769.)
Background:
Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD.
Objective:
We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD.
Methods:
We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English.
Results:
In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application.
Limitations:
We included RCT data only.
Conclusion:
This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.
Proactive therapy for atopic dermatitis (AD) effectively prevents exacerbation. However, its role in preventing subsequent sensitization to allergens has not been prospectively studied. We investigated whether proactive therapy for AD can effectively impact immunological parameters in a randomized, investigator-blinded, parallel group study. Thirty patients aged 3 months to 7 years with moderate to severe AD who had undergone an AD educational program were allocated to a proactive treatment group or a reactive treatment group. During the disease control period, patients in the proactive group performed intermittent preventive application of topical corticosteroid for 1 year. Changes in the severity scoring, quality of life measures and immunological parameters (serum thymus and activation regulated chemokine [TARC], total immunoglobulin E [IgE] and house dust mite-specific IgE levels) were evaluated and compared between the proactive and reactive treatment groups. Although the average topical corticosteroid ointment use per day in both groups was not significantly different, the severity and quality of life scores were significantly lower in the proactive group than in the reactive group at the final visit. In addition, compared with baseline levels, serum TARC levels remained significantly lower during proactive therapy, while house dust mite-specific IgE levels were significantly increased only in the reactive group. The results suggest that in addition to controlling the severity of AD, intermittent preventive administration of topical corticosteroids may prevent an increase in aeroallergen-specific IgE levels in patients with childhood AD. The use of TARC levels as a biomarker for AD remission is also supported.
Objective. To investigate (1) whether the increase in serum creatinine observed during cyclosporin A (CsA) therapy was reversible in a group of patients with rheumatoid arthritis (RA) treated before the current guidelines for safe use in RA were developed and (2) whether the application of these guidelines prevents serum creatinine increases in the long term. Patients and method. Eighty-three RA patients who had started low-dose CsA therapy between September 1990 and October 1992, and who were treated according to guidelines that allowed a 50% rise in serum creatinine, were tested for serum creatinine levels in December 1995 if they had discontinued CsA for at least 3 months. Predictors for irreversibility of renal function were determined by using multiple regression analysis. Result The mean level of serum creatinine gradually increased from 69 ± 14 (mean ± S.D.) μmol/l when starting CsA therapy to 88 ± 23 μmol/l (28% above baseline) at the moment of CsA discontinuation, and had decreased to 80 ± 17 μmol/l (16% above baseline) at follow-up, 35 ± 14 months after drug discontinuation. During CsA therapy, the mean level of serum creatinine had increased to 82 ± 19 μmol/l (26% above baseline) at 6 months and to 87 ± 22 μmol/l (39% above baseline) at 42 months. The mean CsA dose had decreased from 3. 1 ± 0.9 mg/kg/day at 6 months to 1.9 ± 0.8 mg/kg/day at 42 months. The absolute number of months that serum creatinine levels were > 30% above baseline was an independent predictor for a persistent increase of the serum creatinine after CsA discontinuation. More than 2 months with a serum creatinine increase of ≥ 30% resulted in a higher percentage irreversible increase than for less than 2 months with a ≥ 30% increase: 27 and 6%, respectively (P < 0.0001). Conclusion. Long-term low-dose CsA administration in RA patients was associated with an increase in serum creatinine which was partially irreversible after drug discontinuation. The increase in serum creatinine was completely reversible in the patient group that was treated according to the current guidelines for safe use of CsA.
Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.
Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
Unlabelled:
Topical therapy is usually of limited benefit in the treatment of severe atopic dermatitis (AD), and the need for a safe and effective systemic treatment may be required in certain cases especially in children. We evaluated the efficacy and safety of methotrexate and cyclosporine in the treatment of 40 children with severe AD. Patients were divided into two groups (each consisting of 20 patients); group A was treated with methotrexate (7.5 mg/week) while group B was treated with cyclosporine (2.5 mg/kg/day). The severity scoring for atopic dermatitis (SCORAD) was used to indicate efficacy of treatment. In group A, the mean SCORAD score at the beginning of the study was 57.90 ± 3.21 that was reduced at the end of the treatment period to reach 29.35 ± 6.32 with a mean absolute reduction of 26.25 ± 7.03. In group B, the mean SCORAD score was 56.54 ± 4.82 at the start of treatment and was 31.35 ± 8.89 at the end of 12 weeks of treatment. The mean absolute reduction was 25.02 ± 8.21. There was no statistically significant difference in the reduction of SCORAD score between both groups (P ± 0.93). Mild and temporary adverse effects were reported in some patients in both groups.
Conclusion:
Methotrexate or cyclosporine in low doses can be considered as effective, relatively safe, and well-tolerated treatments for severe AD in children.
Background Previous studies suggested that early intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a relapse of atopic dermatitis (AD) following remission may prevent the occurrence of more severe flares and therefore reduce corticosteroid exposure in the long term. However, this possibility was not rigorously evaluated.
Objectives To evaluate the effectiveness of pimecrolimus cream 1% for the prevention of flare progression in adults with AD.
Methods A 26-week randomized controlled study was conducted in 543 patients aged ≥ 18 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 277) or matching vehicle cream (n = 266). Twice-daily treatment with study medication was started at the onset of the first signs and/or symptoms of a relapse. If disease worsened, despite the application of study medication for at least 3 days, treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy endpoint was the number of days without TCS use for disease worsening.
Results The mean number of TCS-free days was significantly higher (P < 0·001) in the pimecrolimus cream 1% group (152 days) than in the vehicle cream group (138·7 days). In comparison with vehicle cream, pimecrolimus cream 1% reduced the mean number of flares requiring TCS use from 1·39 to 0·97 (P = 0·0014). Patients on pimecrolimus cream 1% made 30% fewer unscheduled visits (156) than patients on vehicle cream (223).
Conclusions In adults with a history of mild or moderate AD but free of active skin lesions, intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a subsequent recurrence reduces the number of flares requiring TCS use and decreases the number of disease-related office visits.
Patients with severe atopic eczema frequently require systemic treatment to control their disease. Methotrexate and azathioprine are proposed as off-label treatment options, but direct comparisons are lacking.
We sought to compare the efficacy and safety of methotrexate versus azathioprine in adults with severe atopic eczema.
Patients with severe atopic eczema were randomly assigned in a 1:1 ratio to receive either methotrexate (dosage, 10-22.5 mg/wk) or azathioprine (dosage, 1.5-2.5 mg/kg/d) for 12 weeks, followed by a 12-week follow-up period. Primary outcome was the mean change in the severity scoring of atopic dermatitis index after 12 weeks. Efficacy assessors blinded for allocation of treatment were used to perform clinical outcome assessment. Analyses were done on an intention-to-treat basis.
Of the 45 patients screened, 42 were included. At week 12, patients in the methotrexate group had a mean relative reduction in the severity scoring of atopic dermatitis index of 42% (SD, 18%) compared with 39% (SD, 25%) in the azathioprine group (P = .52). Proportions of patients achieving at least mild disease and reductions on impact of quality of life, symptoms, and levels of thymus and activation-regulated chemokine were similar in both groups at weeks 12 and 24. No statistically significant differences were found in the number and severity of adverse events. Abnormalities in blood count were more common in the azathioprine group. No serious adverse events occurred.
Both treatments achieved clinically relevant improvement and were safe in the short term. Methotrexate and azathioprine are appropriate options for the treatment of severe atopic eczema.
Cyclosporin A (CsA) is frequently used in the treatment of severe atopic dermatitis (AD). Enteric-coated mycophenolate sodium (EC-MPS) may be an alternative with equal efficacy and fewer side effects.
The aim of this observer-blinded randomized controlled trial was to compare EC-MPS with CsA as long-term treatment in adult patients with severe AD.
Fifty five patients with AD were treated with CsA (5 mg/kg) in a 6-week run-in period. Thereafter, patients either received CsA (3 mg/kg; n = 26) or EC-MPS (1440 mg; n = 24) during a maintenance phase of 30 weeks and there was a 12-week follow-up period. Disease activity was measured using the objective SCORAD and serum thymus and activation-regulated chemokine (TARC) levels and side effects were registered.
During the first 10 weeks the objective SCORAD and serum TARC levels in the EC-MPS study arm were higher in comparison with the CsA study arm. In addition, 7 of the 24 patients treated with EC-MPS required short oral corticosteroid courses. During maintenance phase disease activity was comparable in both study arms. Side effects in both study arms were mild and transient. After study medication withdrawal, disease activity of the patients in the CsA study arm significantly increased compared with the EC-MPS study arm.
The nonblinding of patients and prescriber of rescue medication are limitations.
This study shows that EC-MPS is as effective as CsA as maintenance therapy in patients with AD. However, clinical improvement with EC-MPS is delayed in comparison with CsA. Clinical remission after stopping EC-MPS lasts longer compared with CsA.
Rational healthcare decision-making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD).
To evaluate treatment outcomes, resource use and cost associated with twice-weekly tacrolimus 0.03% ointment treatment vs. standard flare-only therapy in children with moderate-to-severe AD.
In a pan-European, Phase III multicentre randomized clinical trial, children with mild-to-severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open-label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate-to-severe AD, with resource use data--collected prospectively using caregiver questionnaires--available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third-party payer, patient and caregiver, and societal perspectives.
Twice-weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean +/- SD annual costs per patient for standard and twice-weekly therapy respectively were 2002 euro +/- 2315 vs. 1571 euro+/- 1122 for severe AD and 1136 euro +/- 1494 vs. 1233 euro +/- 1507 for moderate AD.
In children with AD, twice-weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost-saving in those with severe AD.
The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.
Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction.
The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function.
Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator.
Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period.
Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.
Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations.
This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children.
During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of <or=2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n=125) or vehicle ointment (n=125) twice weekly for 12 months. Exacerbations were treated with 0.03% tacrolimus ointment twice daily until an IGA<or=2 was regained, then randomized treatment was restarted.
The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0.03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1.0; P<0.001; Wilcoxon rank-sum test), the percentage of DE treatment days (median difference: 6.2; P<0.001; Wilcoxon rank-sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P<0.001; stratified log-rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches.
Twice-weekly proactive application of 0.03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.
Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children.
Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopic dermatitis.
One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration.
No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment (p < 0.05).
Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months.
The purpose of this study was to better define the toxicity of low dose (less than or equal to 15 mg/d prednisone or equivalent) long-term (greater than 1 year) corticosteroids in the treatment of rheumatoid arthritis (RA).
We examined an historical cohort of 112 RA patients on low dose (6.1 +/- 3.1 mg/d, mean +/- SD) long-term (6.2 +/- 4.6 years) prednisone (CS) and compared them to 112 matched RA patients not using prednisone (CO). CS were matched one-to-one with CO for sex (75% women), age (+/- 5 yrs), race (98% white), and duration of disease (+/- 5 yrs). Subjects were determined by review of unselected medical records from three distinct rheumatology practice settings. For CS, charts were abstracted from the date of prednisone start for predefined adverse events (AEs).
Ninety-two (92) AEs were noted in CS versus 31 in CO and included: fracture (CS:21 versus CO:8), serious infections (CS:14 versus CO:4), gastrointestinal (GI) bleed or ulcer (CS:11 versus CO:4), and cataracts (CS:17 versus CO:5). At time of first AE, CS prednisone average dose was 7.0 +/- 2.6 mg with a duration of 4.9 +/- 3.9 years. Stepwise multiple logistic regression analysis was used to create a model which included all clinically relevant variables and all parameters significantly different at the cohort inception. Prednisone average dose of greater than 10 to less than or equal to 15 mg/d correlated most strongly with the development of an AE (Odds Ratio (OR) = 32.3, 95% Confidence Interval (CI) 4.6, 220). Average prednisone 5 to 10 mg (OR = 4.5, 95% CI 2.1, 9.6), RA nodules (OR = 3.9, 95% CI 1.9, 8.0), and bony erosions (OR = 2.4, 95% CI 1.2, 4.7) also entered the final model. Kaplan Meier survival curves for the development of the first AE showed a dose-response relationship between prednisone and AE occurrence, independent of rheumatoid nodules. Subset analyses utilized a nested case control design for the development of three serious AEs: fractures, serious infections, and GI events. These analyses revealed possible relationships between prednisone use and the development of each specific AE (prednisone use OR: fracture 3.9, 95% CI 0.8, 18.1; infection 8.0, 95% CI 1.0, 64.0; and GI event 3.3, 95% CI 0.9, 12.1).
Although disease severity is an important confounding factor, low dose long-term prednisone use equal to or greater than 5 mg/d is correlated with the development of specific adverse events in a dose-dependent fashion.
An open, randomized trial was performed to determine the optimal dosage schedule with regard to the efficacy and safety of cyclosporin in severe atopic dermatitis. The study also provided clinical experience with regard to the efficacy and safety of long-term cyclosporin treatment. During a 2-month dose-finding period, 78 patients with severe, long-standing atopic dermatitis received cyclosporin at a dose of either 5 mg/kg per day, decreasing to 3 mg/kg per day (Group A), or 3 mg/kg per day, increasing to 5 mg/kg per day (Group B), Patients were maintained on their optimal dose for a further 10 months. Patients in Group A showed a significantly greater improvement in efficacy parameters over the first 2 weeks than with patients in Group B, but as the dose was decreased in Group A and increased in Group B, these differences were minimized. After 1 year, cyclosporin showed an efficacy of 59.8% in Group A and 51.7% in Group B, assessed by a severity score. Assessed in terms of an area score, these figures were 48.7% and 40%, respectively. Cyclosporin demonstrated a good safety profile during long-term treatment and was generally well tolerated. The lower starting dosage was not associated with higher dropout rates. This study showed no differences in efficacy or adverse events between the two dosage schedules in long-term treatment.
Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.
Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.
Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done.
The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods.
Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies. INCLUSION/EXCLUSION CRITERIA: Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included.
Data extraction was conducted by two observers onto abstraction forms, with discrepancies resolved by discussion. QUALITY ASSESSMENT: The quality assessment of retrieved RCTs included an assessment of: a clear description of method and concealment of allocation of randomisation, the degree to which assessors and participants were blinded to the study interventions, and whether all those originally randomised were included in the final main analysis.
Where possible, quantitative pooling of similar RCTs was conducted using the Cochrane Collaboration's methods. Where statistical heterogeneity was found, sources of heterogeneity in terms of study participants, formulation or posology of intervention, and use of co-treatments were explored. Where pooling was not deemed to be appropriate, detailed descriptions of the study characteristics and main reported results were presented along with comments on study quality.
A total of 1165 possible RCTs were retrieved in hard copy form for further scrutiny. Of these, 893 were excluded from further analysis because of lack of appropriate data. The 272 remaining RCTs of atopic eczema covered at least 47 different interventions, which could be broadly categorised into ten main groups. Quality of reporting was generally poor, and limited statistical pooling was possible only for oral cyclosporin, and only then after considerable data transformation. There was reasonable RCT evidence to support the use of oral cyclosporin, topical corticosteroids, psychological approaches and ultraviolet light therapy. There was insufficient evidence to make recommendations on maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, topical coal tar and topical doxepin. (ABSTRACT TRUNCATED)
The safety and efficacy of 0.03% and 0.1% tacrolimus ointment for the treatment of atopic dermatitis were evaluated in a 12-week, randomized, double-blind, vehicle-controlled study of 351 children 2 to 15 years of age with moderate to severe atopic dermatitis. The mean age of patients was 6.1 years. A total of 61.5% of patients had severe atopic dermatitis at baseline. The mean percentage of body surface area affected was 47.7%, and 83.5% of patients were affected on the head and/or neck. Significantly more patients (P<.001) achieved clinical improvement of 90% or better with 0.03% or 0.1% tacrolimus ointment compared with vehicle. Significant improvements in the signs and symptoms of atopic dermatitis, percent body surface area affected, and the patient's assessment of pruritus were also observed early in treatment and were maintained throughout the study. Adverse events with a statistically significantly greater incidence in the 0.03% tacrolimus ointment treatment group compared with vehicle were limited to the sensation of skin burning, pruritus, varicella, and vesiculobullous rash ("blisters"). Varicella and vesiculobullous rash occurred at a low incidence (<5%). No adverse event occurred at a statistically higher incidence in the 0.1% tacrolimus ointment-treated group compared with vehicle. Tacrolimus ointment was equally safe for younger (2-6 years) and older (7-15 years) children. Both tacrolimus ointment concentrations (0.03% and 0.1%) were safe and significantly more effective than vehicle for the treatment of atopic dermatitis in children.
In two randomized, double-blind, multicenter studies, a total of 631 adult patients with moderate to severe atopic dermatitis applied tacrolimus ointment (0.03% or 0.1%) or vehicle twice daily for up to 12 weeks. The mean percent body surface area (%BSA) affected at baseline was 45%, and 56% of patients had severe atopic dermatitis. As previously reported, these studies showed that tacrolimus ointment was superior to vehicle for all efficacy parameters measured. This report focuses on the safety of tacrolimus ointment in these studies. The most common adverse events were the sensation of skin burning, pruritus, flu-like symptoms, skin erythema, and headache. Skin burning and pruritus were more common among patients with severe or extensive disease; these events were usually brief and were resolved during the first few days of treatment. Common adverse events with a significantly higher incidence in one or both of the tacrolimus ointment groups than in the vehicle group included skin burning, flu-like symptoms, and headache. More patients in the vehicle group discontinued the study because of an adverse event than in either of the tacrolimus ointment groups. There were no notable or consistent changes in any laboratory variables. Tacrolimus was not detected in 80% of blood samples collected. Measurable concentrations of tacrolimus were transitory and were not associated with adverse events. Tacrolimus ointment is a safe therapy for the treatment of adult patients with atopic dermatitis on the face, neck, or other body regions.
A total of 632 adults with atopic dermatitis applied tacrolimus ointment (0.03% or 0.1%) or vehicle twice daily for up to 12 weeks in two randomized, double-blind studies. This report focuses on the efficacy of tacrolimus ointment in these studies. The mean percent body surface area (%BSA) affected at baseline was 45%, and 56% of patients had severe atopic dermatitis. Evaluations included a physician's global evaluation of clinical response, %BSA affected, individual signs of atopic dermatitis, the Eczema Area and Severity Index (EASI) score, and the patient's assessment of pruritus. A 90% or greater improvement from baseline in disease status was observed for 6.6%, 27.5%, and 36.8% of patients in the vehicle, 0.03% tacrolimus ointment, and 0.1% tacrolimus ointment groups, respectively (P<.001), and 50% or better improvement was observed for 19.8%, 61.6%, and 72.7% of patients, respectively. Tacrolimus ointment-treated patients showed significantly greater improvement than vehicle-treated patients for all efficacy parameters evaluated, including the %BSA affected, the total score and individual scores for signs of atopic dermatitis, the patient's assessment of pruritus, and EASI score. The 0.1% concentration was more effective than the 0.03% concentration, particularly in patients with severe disease and/or extensive BSA involvement at baseline and in African Americans. Tacrolimus ointment is an effective therapy for the treatment of adult patients with atopic dermatitis on all skin regions including the head and neck.
Although cyclosporin is effective for the treatment of severe atopic dermatitis, phototherapy is the standard second-line treatment for this disease. An open, randomized, controlled, parallel-group study was conducted to compare the efficacy, influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients. The main endpoints of the study were the number of days in remission and the influence on quality of life. Seventy-two patients were treated, 36 in each group. Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period. At the end of the study no difference between the 2 groups was noted in terms of quality of life. A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment. It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period.
Narrow-band ultraviolet B (UVB) is an effective treatment for psoriasis, and open studies suggest that this phototherapy might improve atopic eczema. We did a randomised controlled trial to compare narrow-band UVB, UVA, and visible light phototherapy as second-line, adjunctive treatments in adult patients with moderate to severe atopic eczema.
Phototherapy was administered twice a week for 12 weeks. 26 patients were randomly assigned narrow-band UVB, 24 were assigned UVA, and 23 visible fluorescent light. The primary endpoints were change in total disease activity (sum of scores at six body sites) and change in extent of disease after 24 treatments compared with baseline. Data were analysed by the method of summary measures.
13 patients withdrew or were excluded from analysis. Mean reductions in total disease activity over 24 treatments in patients who received narrow-band UVB and UVA, respectively, were 9.4 points (95% CI 3.6 to 15.2) and 4.4 points (-1.0 to 9.8) more than in patients who received visible light. Mean reductions in extent of disease after 24 treatments with narrow-band UVB and UVA were 6.7% (1.5 to 11.9) and -1.0% (-5.3 to 3.3) compared with visible light. A small proportion of patients developed erythema after phototherapy or had a flare in their eczema sufficient to withdraw from treatment.
Narrow-band UVB is an effective adjunctive treatment for moderate to severe atopic eczema, and the treatment is well tolerated by most patients.
Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control.
The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.
In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months.
Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups.
Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.
There is a limited range of treatments for severe atopic dermatitis (AD). Azathioprine has often been used but there has been no randomized controlled trial of this drug to confirm its efficacy in AD.
To establish or refute the efficacy of azathioprine in severe AD. To investigate the safety and tolerability of azathioprine in this patient population.
We performed a double-blind, randomized, placebo-controlled, crossover trial of azathioprine in adult patients with severe AD. Each treatment period was of 3 months' duration. Treatments were azathioprine 2.5 mg kg(-1) day(-1) and matched placebo. Disease activity was monitored using the SASSAD sign score. In addition, severity of pruritus, sleep disturbance and disruption of work/daytime activity were monitored using visual analogue scales. Adverse events were recorded and haematological and biochemical monitoring was performed.
Thirty-seven subjects were enrolled, mean age 38 years (range 17-73). Sixteen were withdrawn, 12 during azathioprine treatment and four during placebo treatment. The SASSAD score fell by 26% during treatment with azathioprine vs. 3% on placebo (P < 0.01). Pruritus, sleep disturbance and disruption of work/daytime activity all improved significantly on active treatment but not on placebo. The difference in mean improvement between azathioprine and placebo was significant for disruption of work/daytime activity (P < 0.02) but not for pruritus or sleep disturbance. Gastrointestinal disturbances were reported by 14 patients during azathioprine treatment and four were withdrawn as a result of severe nausea and vomiting. Leukopenia was observed in two patients and deranged liver enzymes in eight during treatment with azathioprine.
Azathioprine is an effective and useful drug in severe AD although it is not always well-tolerated. Monitoring of the full blood count and liver enzymes is advisable during treatment.
One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease.
To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD.
Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score </= 2, erythema, pruritus, and papulation/induration/oedema scores </= 1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring.
A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7.7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel-Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4.6, 12.8; P < 0.001]. Paediatric subjects were 8.1 times less likely to have an AD relapse (95% CI 4.3, 15.2; P < 0.001) and adult subjects were 7.0 times less likely to have an AD relapse (95% CI 3.0, 16.7; P < 0.001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4.7 weeks. For paediatric and adult groups, this was 5.1 and 4.1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects.
In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy.
Pimecrolimus cream (Elidel, SDZ ASM 981), a non-steroid inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms reduces the need for topical corticosteroids.
To investigate the efficacy and safety of pimecrolimus cream 1% in the long-term management of adult AD.
192 adults with moderate to severe AD were randomised (1:1) for twice daily (b.i.d.) treatment of early signs or symptoms of AD with either pimecrolimus cream 1% or vehicle cream (control group) to prevent progression to flares. Treatment was given as needed for 24 weeks. In the event of flares, a moderately potent corticosteroid (prednicarbate 0.25% cream) was permitted as rescue medication in both groups. The percentage of days on which a topical corticosteroid was used to treat disease flares was the main outcome measure.
Corticosteroid medication was used on 14.2% (95% confidence interval, CI: 8.3-21.1) of the days of the 24-week treatment period in the pimecrolimus group and on 37.2% (95% CI: 30.4-44.0) of the days in the control group (p < 0.001). In total, 44.8% (43/96) of patients in the pimecrolimus group did not experience a flare compared with 18.8% (18/96) of patients in the control group. The median time to first flare was 144 days in the pimecrolimus group and 26 days in the control group (p < 0.001). Pimecrolimus treatment was also associated with improvement in signs and symptoms of AD, pruritus, patients' self-assessment and quality of life.
Pimecrolimus cream 1% b.i.d. is an effective, well-tolerated, long-term treatment for AD in adults, substantially reducing the number of flares compared to a conventional therapy and consequently reducing or eliminating the need for corticosteroid treatment.
To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis.
Randomised, double blind, parallel group study of 20 weeks' duration.
Dermatology outpatient clinics (6 countries, 39 centres).
Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare.
Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected.
Time to relapse of atopic dermatitis during maintenance phase.
376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events.
After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.
Two multicentre, randomised, parallel group, double-blind, comparative studies in children (2-14 yr) evaluated fluticasone propionate (FP) 0.05% cream for both acute and maintenance treatment of moderate to severe atopic dermatitis (AD).
One study compared FP with hydrocortisone (HC) 1% cream (FP 70, HC 67) and the other with hydrocortisone butyrate (HCB) 0.1% cream (FP 67, HCB 62). Treatments were applied twice daily, for 2-4 weeks until the AD was stabilised, and thereafter intermittently ('as required') for up to 12 weeks.
The primary outcome measure, Total AD Score, recorded at the end of the acute and maintenance phases, was significantly lower (indicating improvements in disease severity) following treatment with FP compared with either HC or HCB (acute phase difference vs. HC, -2.39, 95%CI -3.47, -1.31; p<0.001 and vs. HCB, -1.25, 95%CI -2.46, -0.05; p=0.042) and (maintenance phase difference vs. HC, -1.88, 95%CI -3.20, -0.56; p=0.006 and vs. HCB, -1.39, 95%CI -2.72, -0.05; p=0.042). In both studies treatments were equally well tolerated with no visible signs of skin atrophy.
In both the acute and longer term management of AD in children, FP demonstrated a high level of efficacy and maintenance of disease control with a tolerability similar to HC 1%, a lower potency corticosteroid.