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Baricitinib in the Treatment of Severe Atopic Dermatitis Resistant to Cyclosporine: A Case Report Involving Two Cases
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder that profoundly affects quality of life, particularly in patients with moderate-to-severe disease that is refractory to conventional treatments.
Cyclosporine is a cornerstone of systemic therapy for severe AD; however, its long-term use is hindered by toxicity, and effective alternatives are often unavailable or insufficient. Janus kinase inhibitors, including baricitinib, have emerged as promising therapeutic options by modulating key inflammatory pathways involved in AD pathogenesis. This report describes two cases of severe cyclosporine-refractory AD that were successfully managed with baricitinib. Both patients showed substantial clinical improvement, including significant reductions in affected body surface area, disease severity scores, pruritus, and sleep disturbances
within four weeks of initiating treatment. No serious adverse effects were observed, and the treatment was well tolerated. These findings highlight the potential of baricitinib as a viable therapeutic alternative for severe AD, particularly in settings where biologics such as dupilumab or abrocitinib may be limited. While
baricitinib demonstrates both rapid and sustained efficacy, further studies are warranted to confirm its longterm safety and define its optimal role in AD management.
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Background
Baricitinib treatment in adults with moderate‐to‐severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest.
Objectives
In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials.
Methods
We analysed the percent change from baseline in individual EASI subscores from three phase‐III, double‐blind, 16‐week trials of baricitinib in monotherapy (BREEZE‐AD1/BREEZE‐AD2) and TCS combination therapy (BREEZE‐AD7) cohorts via mixed model repeated measures (MMRM).
Results
Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near‐maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy.
Conclusions
Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch‐scratch cycle.
Atopic dermatitis (AD) is a common chronic dermatological condition affecting ~10% of
adults and ~20% of the paediatric population in high‑income countries. There is a lack of comprehensive understanding of the disease burden of AD in India. In this systematic review, the primary objective was to review epidemiological data on AD in India based on articles published between 2011 and 2021. The secondary objective was to assess the disease burden from economic and quality of life (QoL) perspectives. A literature search was conducted using the PubMed and Google Scholar databases using predefined search strings. Relevant studies published in English on AD between 2011 and 2021 were included. This review included
11 articles, of which nine reported demographic and clinical characteristics. The reported prevalence ranged from 3.1% to 7.21% among the paediatric population, up to 16 years of age. The prevalence of AD ranged from 0.98% to 9.2% in studies including paediatric and adult patients. The cost of medications was reported to be the major contributor to the economic burden associated with AD. Mental illnesses such as depression and anxiety were frequently reported in association with AD. Although AD is a common disorder affecting all age groups, there is a lack of substantial epidemiological data. None of the current studies covers the entire country. Hence, studies with a wider geographic scope covering all aspects of disease burden are required to help clinicians and policymakers to understand the disease burden and
devise appropriate preventive and management strategies.
The article entitled “Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials” that belongs to the Special Issue, “ Personalized medicine in the field of inflammatory skin diseases”, a collection of articles addressing the current critical issues in the pathogenesis and management of chronic inflammatory skin disorders, represents a valuable work that has contributed to elucidating the role of Janus kinase (JAK) inhibitors as a treatment option for atopic dermatitis (AD), as well as their safety profiles [...]
Atopic dermatitis (AD) is a chronic inflammatory dermatosis with periods of exacerbation and remissions. AD is characterized by intense, persistent pruritus and heterogeneity in clinical symptomatology and severity. Therapeutic goals include the amelioration of cutaneous eruptions, diminishing relapses and eventually the disease burden. To date, topical corticosteroids (TCS) and calcineurin inhibitors (TCI) have yet been deemed the mainstay of topical treatments in AD management. Nevertheless, despite their indisputable efficiency, TCS and TCI are not indicated for continuous long-term use given their safety profile. While research in AD has concentrated predominantly on systemic therapies, more than 30 novel topical compounds are under development. The existing data appear encouraging, with some regimens that are already FDA-approved (ruxolitinib was the most recent in September 2021) and several pharmaceutical pipeline products for mild-to-moderate AD that are in an advanced stage of development, such as tapinarof, difamilast and roflumilast. Larger, long-term studies are still required to evaluate the efficacy and safety of these novel compounds in the long run and weigh their advantages over present treatments. In this review, we aim to provide an overview of the latest knowledge about AD topical treatments, echoing upcoming research trends.
Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.
Background
Atopic dermatitis (AD) is a chronic inflammatory, non-communicable, and relapsing skin disease that affects all age groups. There is a dearth of literature that reports the disease burden, and epidemiology and highlights unmet needs in the diagnosis and management of AD in India.
Methods
A total of ten specialists including dermatologists, pediatric dermatologists, and pediatricians with more than ten years of experience and practicing in different parts of India served as the expert panel during the virtual meet conducted on January 24, 2021. A questionnaire comprising 32 questions on different aspects of AD management was categorized among different sections: burden of disease (five questions), age of onset and prevalence (five questions), etiology and pathogenesis (six questions), diagnosis and severity of the disease (seven questions), and treatment (nine questions). Consensus was defined when agreement was provided by ≥90% of the experts.
Results
Considering the profound impact AD has on the quality of life (QoL) of patients, the expert panel recommended patient counseling while moderate to severe cases of AD need a prompt referral to a specialist. The panel did not recommend any specific diagnostic and severity criteria as a standard due to the inherent limitations associated with every criterion. The role of environment and changing lifestyle in addition to genetic and familial risk factors for AD was also considered. The panel unanimously recommended to conduct a countrywide, multicenter survey/study to estimate the true prevalence of AD in India. Further, the experts recommended to follow proper treatment protocols and to perform longitudinal monitoring for understanding corticosteroid treatment associated side effects.
Conclusion
This guidance focuses on identifying the unmet gaps and provides practical recommendations for improving QoL, diagnosis, prognosis, and overall management of patients with AD in India.
Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by a wide phenotypic variety with a very complex pathophysiological mechanism that has led to the identification of new therapeutic targets, such as janus kinasis (JAK) inhibitors. Objectives: To evaluate the efficacy and safety of baricitinib, the first JAK 1 and 2 inhibitor approved in Europe for the treatment of adult patients with moderate-to-severe AD. Methods: The efficacy and safety data available from the Phase III studies belonging to the BREEZE AD program are presented. Results: Results from BREEZE-AD1, AD2, AD4, and AD7 showed the efficacy of Baricitib 4 mg, administered orally, once daily, as monotherapy or in combination with topical corticosteroid (TCS), with a significant proportion of patients achieving primary endpoints IGA 0–1 (16.4% vs. 4.8%; 13.8% vs. 4.5%; 21.7% vs. 9.7%; 30.6% vs. 14.7%) and EASI75 (24.8% vs. 8.8%; 21.1% vs. 6.1%; 31.5% vs. 17.2%; 47.7% vs. 22.9%) at week 16 (W16) compared to placebo, respectively. Baricitinib showed rapid improvement in symptoms, starting from week 1 of treatment at 4 mg dosage, with a good safety profile. Nasopharyngitis, upper respiratory tract infections (URIs), creatine phosphokinase (CPK) elevations, and headache were the most frequently reported adverse events. Conclusions: Following the efficacy and safety data on W 16 from the phase III BREEZE-AD studies, baricitinib has recently been approved in Europe for the treatment of moderate to severe AD in adult patients. Further data to evaluate long-term efficacy and safety in a real-life setting are needed.
Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6–24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.
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.
The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a key regulatory signaling system for cellular proliferation, differentiation, and apoptosis. In addition, JAK signaling pathway plays critical roles in orchestrating immune response through its interactions with the cytokine receptors and the transcriptions factors. Several key cytokines use JAK-STAT signaling proteins to transduce intra-cellular signals which are involved in the pathogenesis of autoimmune and inflammatory diseases such as in psoriatic disease (psoriasis, psoriatic arthritis), atopic dermatitis, alopecia areata, vitiligo, rheumatoid arthritis, ankylosing spondylitis, lupus erythematosus, Sjogren’s syndrome, and other autoimmune diseases. In recent years, understandings of the molecular mechanisms of JAK-STAT pathway in the inflammatory proliferative cascades of autoimmune diseases has led to the development of JAK inhibitors and has opened a new dimension for the treatment of systemic and cutaneous inflammatory diseases. In this symposium we have provided a broad perspective on the use of Janus kinase inhibitors in cutaneous autoimmune diseases.
The authors evaluated the efficacy and safety of baricitinib, a Janus kinase 1/2 inhibitor, for atopic dermatitis (AD) in real‐world practice. From August 2021 to September 2022, 36 patients aged ≥15 years with moderate to severe AD were treated with oral baricitinib 4 mg/day plus topical corticosteroids. Baricitinib improved clinical indexes; the percent reduction at weeks 4 and 12 was a median of 69.19% and 69.98% for the Eczema Area and Severity Index (EASI), 84.52% and 76.33% for the Atopic Dermatitis Control Tool, and 76.39% and 64.58% for Peak Pruritus Numerical Rating Score, respectively. The achievement rate of EASI 75 was 38.89% and 33.33% at weeks 4 and 12, respectively. The percent reduction of EASI in the head and neck, upper limbs, lower limbs, and trunk was 56.9%, 68.3%, 80.7%, and 62.5% at week 12, respectively, with a significant difference between the head and neck versus the lower limbs. Baricitinib decreased thymus and activation‐regulated chemokine, lactate dehydrogenase, and total eosinophil count at week 4. Baseline EASI of the head and neck negatively correlated with percent reduction of EASI at week 4, while baseline EASI of the lower limbs positively correlated with percent reduction of EASI at week 12. Treatment‐emergent adverse events included elevation of creatine phosphokinase (11.1%), herpes labialis (5.6%), furuncle (8.3%), and exacerbation of AD (1%), without serious treatment‐emergent adverse events. In this real‐world study, baricitinib was well tolerated for patients with AD and achieved therapeutic effects comparable to those in clinical trials. High baseline EASI of the lower limbs might predict good treatment response at week 12, while high baseline EASI of the head and neck might predict poor treatment response at week 4 in baricitinib treatment for AD.
Background
Baricitinib, an oral, selective Janus kinase (JAK)1/JAK2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults.
Objective
To evaluate the efficacy and safety of baricitinib monotherapy in a North American Phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy.
Methods
Patients (N=440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index (EASI75) at Week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD (vIGA-AD™) score of 0 (clear)/1(almost clear) with ≥2-point improvement.
Results
At Week 16, the proportion of patients achieving EASI75 was 8%, 13%, and 30% (P <.001, 2 mg vs. placebo) and those with a vIGA-AD 0/1 were 5%, 13%, and 24% (P <.001, 2 mg vs. placebo), for placebo, baricitinib 1 mg, and 2 mg, respectively. Safety findings were similar to other baricitinib AD studies.
Limitations
Short-term clinical trial results may not be generalizable to real-world settings.
Conclusion
Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks.
Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores
- A Wollenberg
- D Simon
- K Kulthanan
- Wollenberg A