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ABSTRACT: The efficacy of the two-compound formulation (TCF) product containing calcipotriol and betamethasone dipropionate applied once daily in psoriasis has been demonstrated in phase III trials but no randomised clinical trial comparing all commonly used topical treatments exists. The aim of the study was to compare the efficacy of once-daily use of the TCF product relative to other commonly used topical agents in plaque psoriasis.
Data on change in Psoriasis Area and Severity Index (PASI) score from baseline and PASI 75 (percentage of patients achieving a 75% reduction in PASI score), after 4 weeks of treatment were obtained by means of a systematic literature review of randomised controlled trials and synthesised with a Bayesian mixed treatment comparison meta-analysis.
Relative to all active interventions, except for the unlicensed twice-daily application of the TCF product, the TCF once daily showed a greater efficacy based on PASI 75 response (relative risk ranging from 1.22 to 3.18) and improvement in PASI score from baseline (difference in % CFB PASI between TCF once daily and other active interventions ranged from 4.01 to 49.68).
Among topical therapies evaluated, TCF once daily can be considered the most efficacious treatment for plaque psoriasis.
Current Medical Research and Opinion 01/2011; 27(1):225-38. · 2.38 Impact Factor
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Peter van de Kerkhof,
Jonathan Barker,
Christopher E M Griffiths,
Alan Menter,
Craig Leonardi,
Melodie Young,
Lajos Kemeny,
Carlo Pincelli,
Hervé Bachelez,
Andreas Katsambas,
Mona Ståhle,
Elizabeth J Horn,
Wolfram Sterry
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ABSTRACT: Clinical trials to test investigational drugs for the treatment of chronic plaque psoriasis currently lack standards for comparison of efficacy and safety data.The majority of studies do not address the important need for long-term treatment.
The International Psoriasis Council (IPC) conducted two surveys of its members to assess the need for gold standards, active comparators, and long-term therapy in clinical trials. In Survey 1, 30 participants delivered viewpoints on active comparators for topical therapy (six questions), systemic therapy (nine questions), and continuous versus intermittent therapy (six questions). In Survey 2, 31 participants provided input on gold standards for treatment (five questions), appropriate comparators (four questions), and continuous versus intermittent therapy (six questions). The IPC leadership interpreted the results after each survey.
The majority of participants (77% in Survey 1 and 89% in Survey 2) agreed that studies of investigative treatments should include an active comparator. Participants described the most important feature of a gold standard as a treatment that: is widely used and generally accepted (45%); has the best efficacy (42%); and is well tolerated (13%). The majority agreed that gold standards should be dependent on: patient subgroup; location/extent of psoriasis; and psoriasis subtype/morphology. It was also agreed that continuous therapy for more than 3 years is needed for patients with moderate-to-severe plaque psoriasis. We have provided an expert opinion regarding the definition of a gold standard in psoriasis and have also established that no single treatment can be the gold standard across all subgroups and types of the disease.
A single gold standard for the treatment of psoriasis does not exist. The complexity and heterogeneity of psoriasis requires different gold standards for the various manifestations of psoriasis and for subgroups of patients reconciling comorbidities. Of note, 17 experts out of 30 selected methotrexate as the most nominated gold standard amongst systemic agents. The experts support the election of an active comparator as one that is most efficacious over just the best in a particular class. In concordance, 87% of respondents agreed that good tolerability is therefore not the lead criterion for selection of an active comparator in favor of effectiveness and broad use. Patients with moderate-to-severe plaque psoriasis require continuous therapy; this statement was supported by 93% of the experts. Reasons for considering long-term therapy included appearance of comorbidities, impairment of quality of life, possibility of relapse, and subjective complaints such as itch, pain, and joint disease.
Journal of Dermatological Treatment 10/2010; 22(4):187-93. · 1.23 Impact Factor
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ABSTRACT: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated.
To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe plaque psoriasis.
A total of 912 patients received 50 mg subcutaneous etanercept once weekly (OW) for the first 12 weeks of this extension study. Thereafter, eligible patients could maintain the 50 mg QW dose (n = 321) or escalate to 50 mg twice weekly (BIW; n = 591) anytime thereafter based on one of three predetermined criteria.
Etanercept was well tolerated during 1056 patient-years of exposure; no difference was observed between the 50 mg QW and 50 mg BIW dosages in rates of adverse events and infections. Improvement in skin disease was maintained throughout the study. Patients who stopped and then restarted etanercept also showed improvement in psoriasis.
Psoriatic patients continued to benefit from open-label etanercept treatment, both continuous and interrupted therapy, which was generally well tolerated after a combined 2.5 years of experience.
Journal of drugs in dermatology: JDD 08/2010; 9(8):928-37. · 1.57 Impact Factor
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Christopher E M Griffiths,
Bruce E Strober, Peter van de Kerkhof,
Vincent Ho,
Roseanne Fidelus-Gort,
Newman Yeilding,
Cynthia Guzzo,
Yichuan Xia,
Bei Zhou,
Shu Li,
Lisa T Dooley,
Neil H Goldstein,
Alan Menter
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ABSTRACT: Biologic agents offer a range of new therapeutic options for patients with psoriasis; however, the relative benefit-risk profiles of such therapies are not well known. We compared two biologic agents, ustekinumab (an interleukin-12 and interleukin-23 blocker) and etanercept (an inhibitor of tumor necrosis factor alpha), for the treatment of psoriasis.
We randomly assigned 903 patients with moderate-to-severe psoriasis to receive subcutaneous injections of either 45 or 90 mg of ustekinumab (at weeks 0 and 4) or high-dose etanercept (50 mg twice weekly for 12 weeks). The primary end point was the proportion of patients with at least 75% improvement in the psoriasis area-and-severity index (PASI) at week 12; a secondary end point was the proportion with cleared or minimal disease on the basis of the physician's global assessment. Assessors were unaware of the treatment assignments. The efficacy and safety of a crossover from etanercept to ustekinumab were evaluated after week 12.
There was at least 75% improvement in the PASI at week 12 in 67.5% of patients who received 45 mg of ustekinumab and 73.8% of patients who received 90 mg, as compared with 56.8% of those who received etanercept (P=0.01 and P<0.001, respectively). Similarly, 65.1% of patients who received 45 mg of ustekinumab and 70.6% of patients who received 90 mg of ustekinumab had cleared or minimal disease according to the physician's global assessment, as compared with 49.0% of those who received etanercept (P<0.001 for both comparisons). Among patients who did not have a response to etanercept, 48.9% had at least 75% improvement in the PASI within 12 weeks after crossover to ustekinumab. One or more adverse events occurred through week 12 in 66.0% of patients who received 45 mg of ustekinumab and 69.2% of patients who received 90 mg of ustekinumab and in 70.0% who received etanercept; 1.9%, 1.2%, and 1.2%, respectively, had serious adverse events. Safety patterns were similar before and after crossover from etanercept to ustekinumab.
The efficacy of ustekinumab at a dose of 45 or 90 mg was superior to that of high-dose etanercept over a 12-week period in patients with psoriasis. (ClinicalTrials.gov number, NCT00454584.)
New England Journal of Medicine 01/2010; 362(2):118-28. · 53.30 Impact Factor
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ABSTRACT: Psoriasis lesions accumulate protoporphyrin IX (PpIX) with a variable distribution within plaques due to variations in hyperkeratosis causing differences in penetration of cream or light. Objectives: To study the effects of different keratolytic pretreatments in PpIX-induced fluorescence diagnosis (FDAP) and during photodynamic therapy (PDT).
Two psoriasis plaques of 10 patients were treated with either topical retinoic acid or with a hydrocolloid dressing. The hydrocolloid dressing gave the best results. Subsequently, two different contralateral plaques of eight patients were pretreated with a hydrocolloid dressing or the standard pretreatment, salicylic acid in petrolatum, during the 6 weeks of PDT. Biopsies were investigated with respect to stratum corneum thickness, proliferation, differentiation and inflammation.
Irritation and point bleedings were noticed after retinoic acid. A hydrocolloid dressing induced the best clinical improvement. Therefore, it was used as alternative pretreatment for psoriasis prior to PDT. We observed significant clinical and immunohistochemical improvement of psoriasis in the salicylic acid as well as the hydrocolloid dressing pretreated plaques.
Salicylic acid in petrolatum and a hydrocolloid dressing prior to FDAP and PDT induce improvement of hyperkeratosis. Thus, a hydrocolloid dressing is a good alternative to the current keratolytic pretreatment regime.
Journal of Dermatological Treatment 10/2009; 21(4):245-51. · 1.23 Impact Factor
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ABSTRACT: A study was conducted to explore the epidemiology of childhood psoriasis in general practitioners (GPs) and dermatological practice in the region of our academic medical centre. The treatments used by GPs and dermatologists in juvenile psoriasis were investigated.
A questionnaire was sent to 229 GPs and 73 dermatologists. Questions were addressed about the prevalence of childhood psoriasis and treatments used in this disease.
Seventy-three questionnaires were completed. The response rate was 17.0% for GPs and 46.6% for dermatologists. Almost one-third of all GPs have seen one or more patients with juvenile psoriasis under the age of 11 in their own patient population, in contrast to more than 80% of the dermatologists. Extrapolating the results implied an estimated prevalence of childhood psoriasis of 0.17% in the overall Dutch population. Topical corticosteroids were used by 46.2% of GPs and by 91.2% of dermatologists. Vitamin D analogues were prescribed by GPs and dermatologists in 15.4% and 73.5% of cases, respectively. Systemic medication for juvenile psoriasis was only used by 20.6% of dermatologists.
Calculated for the Dutch population, there should be approximately 27,500 children with psoriasis in The Netherlands. Topical corticosteroids were the first-choice treatment for both GPs and dermatologists, whereas vitamin D analogues were used as a second-choice topical therapy. Systemic medication was only sparsely prescribed by dermatologists.
Journal of Dermatological Treatment 02/2009; 20(5):254-8. · 1.23 Impact Factor
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ABSTRACT: The purpose of this study was to achieve a validated clinical and image scoring system for a single chronic discoid lupus erythematosus (CDLE) lesion.
Fifteen patients with a CDLE lesion were scored twice by four observers and clinical photographs were taken. These pictures were assessed by the same four observers at two time points. Patients were scored using the DLE-Skin Score (DLE-SS). In addition, the DLE-Photo Score (DLE-PS) was calculated. Statistical analysis was carried out by measuring inter- and intra-observer agreement for both methods and by measuring the correlation between the DLE-SS and DLE-PS.
Both the DLE-SS and DLE-PS proved reliable methods in the assessment of CDLE. The inter-observer variability of the DLE-SS and DLE-SS was low. The intra-observer variability was estimated to be 0 in both methods. The correlation coefficient between the DLE-SS and DLE-PS was high (0.81).
Both the DLE-SS and the DLE-PS are reliable and easy-to-use methods to score disease activity in CDLE patients, and can be used in monitoring single target lesions in clinical trials.
Journal of Dermatological Treatment 07/2008; 20(1):32-5. · 1.23 Impact Factor
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ABSTRACT: Objectives: The most recently introduced therapeutics for psoriasis are biologicals which can target the T-cell-mediated pathology of psoriasis in a direct or indirect manner. The present pilot study focuses on and compares the effect of a conventional systemic agent (methotrexate; MTX) with the effect of a TNF-binding biological (adalimumab) on psoriasis-associated T-cell subsets in peripheral blood (PB) and lesional skin. Insight is provided in the hypothesized compartmentalization of these T-cell subsets between PB and the cutaneous compartment. Methods: Immunohistochemical stainings of designated T-cell subsets on psoriatic skin sections were performed and similar subsets were isolated from PB specimens by flow cytometry. These counts were correlated with clinical severity. Results: Results showed that adalimumab had a greater clinical effect than MTX treatment after 12 weeks. In the dermis, only the CD3+ T cells were significantly reduced after 12 weeks of adalimumab therapy, whereas for MTX only CD3+ T cells in the epidermis and CD45RO+ T cells in the dermis reduced significantly. However, PB T-lymphocyte populations did not show significant shifts in quantification of T-cell subsets. Conclusion: Therefore, recompartmentalization of psoriasis-associated T-cell subsets between PB and lesional skin was not induced in this study as a therapeutic principle. Consequently, recompartmentalization of T-cell subsets does not seem an obligatory event in order to achieve good clinical response.
Journal of Dermatological Treatment 05/2008; · 1.23 Impact Factor
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ABSTRACT: To evaluate the safety and efficacy of multiple courses of alefacept in combination with traditional psoriasis therapy for the treatment of chronic plaque psoriasis (CPP).
Patients with CPP requiring systemic therapy were eligible for this study. Patients received up to three courses of intramuscular alefacept 15 mg once weekly for 12 weeks. One concomitant psoriasis therapy (topical agents, methotrexate, cyclosporine, systemic retinoids, or ultraviolet B [UVB]) per course was allowed. The extent of disease was determined using the 7-point Physician Global Assessment (PGA; scale ranging from 0 = clear to 6 = severe).
More than 73% of patients improved by > or = one PGA category and > or = 44% of patients improved by > or = two PGA categories across all concomitant treatments. Clinical responses tended to be greatest in patients who received alefacept plus UVB. The incidences of serious infections (< or =1%) and malignancies (< or =2%) were low across all courses and all combinations.
Multiple courses of alefacept appear to be well tolerated and demonstrate efficacy in patients with CPP when administered with other psoriasis therapies.
Journal of Dermatological Treatment 02/2008; 19(3):146-55. · 1.23 Impact Factor
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Peter van de Kerkhof
Journal of Dermatological Treatment 02/2008; · 1.23 Impact Factor
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ABSTRACT: Patients with leg ulceration often have long lasting and recurrent wounds. The treatment exists mainly of wound-care and compression therapy. International literature shows several indications of problems in relation to leg ulceration, but no studies were performed to give a comprehensive overview of all problems identified and care received related to these problems.
The aim of the study was to describe leg ulcer-related problems in patients with leg ulcers based on venous insufficiency or a mixed aetiology. Furthermore, an inventory of current care and care deficits in the care for leg ulcer patients was made.
The study had a descriptive, cross-sectional design. A sample of 141 patients was taken from the population of outpatient clinics of seven hospitals in the Netherlands. Data were collected through patient interviews, questionnaires and wound-observations. Medical information was provided by the dermatologist or derived from the patients' medical file.
The study identified a number of serious problems. Main problems were pain (85%), outdoor mobility (47%) and problems in finding appropriate footwear (60%). Statistical analysis showed no differences between patients with ulcers based on a venous aetiology and ulcers based on mixed aetiology. Fifty to seventy percent of the patients did not receive any care in relation to these problems. Only a rather small proportion of the patients, however, regarded the help as insufficient.
Care at outpatient clinics is mainly focused on wound care and compression therapy. Pain treatment and care related to problems encountered by patients appears to be insufficient. This is not only affecting the patient's quality of life, but is likely to affect also the healing process and prevention of leg ulcers. Nurses and dermatologist should take their responsibilities in this matter.
International Journal of Nursing Studies 12/2007; 44(8):1296-303. · 2.18 Impact Factor
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ABSTRACT: The objective of our project was to develop a lifestyle program for leg ulcer patients at outpatient clinics for dermatology.
We used the intervention-mapping (IM) framework for systematically developing theory and evidence based health promotion programs. We started with a needs-assessment. A multidisciplinary project group of health care workers and patients was involved in all five IM steps; formulating proximal program objectives, selecting methods and strategies, producing program components, planning for adoption and implementation and planning for evaluation. Several systematic literature reviews and original studies were performed to support this process.
Social Cognitive Theory was selected as the main theory behind the program 'Lively Legs' and was combined with elements of Goal-Setting Theory, the precaution adoption model and motivational interviewing. The program is conducted through health counseling by dermatology nurses and was successfully pre-tested. Also, an implementation and evaluation plan were made.
Intervention mapping helped us to succeed in developing a lifestyle program with clear goals and methods, operational strategies and materials and clear procedures.
Coaching leg ulcer patients towards adherence with compression therapy and healthy lifestyles should be taken on without delay. Systematic development of lifestyle programs for other patient groups should be encouraged.
Patient Education and Counseling 06/2006; 61(2):279-91. · 2.31 Impact Factor
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ABSTRACT: It is well-known that cognitive, behavioral, and physiological reactivity to pain, such as catastrophizing, avoidance of activity, and increased physiological responses, can unfavorably affect long-term outcomes in patients with chronic pain. In line with similarities between the psychophysiology of pain and itching, corresponding mechanisms may be relevant for the maintenance of chronic itching. The goal of this study was to examine the role of self-reported cognitive, behavioral, and physiological reactivity factors on itching-related outcomes in 235 patients with chronic skin diseases suffering from chronic itching. Sequential regression analyses indicate that all 3 reactivity systems predicted itching-related outcomes. Specifically, more catastrophizing, higher levels of avoidance of activity, and heightened self-reported physiological reactivity predicted more itching, more scratching, and a reduced disease-related quality of life. The results suggest that a psychological model as described for chronic pain is a useful starting point for study of the maintaining mechanisms of chronic itching.
International Journal of Behavioral Medicine 02/2006; 13(3):237-43. · 2.63 Impact Factor
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Peter van de Kerkhof
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ABSTRACT: The most frequently used systemic treatments for severe psoriasis are methotrexate (MTX), oral retinoids, and cyclosporine; however, all of these agents are associated with dose-related toxicities that limit their use. The safety and efficacy of topical calcipotriene for the treatment of psoriasis have been demonstrated in numerous clinical studies. The rationale for using calcipotriene in combination with systemic therapies is based on their different modes of action and nonoverlapping side effects. Three controlled clinical trials have demonstrated that the addition of calcipotriene ointment to systemic antipsoriatic treatment with MTX, acitretin, and cyclosporine increases the therapeutic efficacy compared with systemic therapy alone and minimizes side effects by either reducing the dosage or duration of treatment.
Cutis; cutaneous medicine for the practitioner 12/2002; 70(5 Suppl):16-20. · 0.81 Impact Factor
