Effectiveness of Abrocitinib in Cyclosporine-Resistant Atopic Dermatitis: A Real-world Experience from the Indian Subcontinent

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and eczematous lesions. Abrocitinib, a selective Janus kinase 1 (JAK1) inhibitor, has recently been approved in India for moderate-to-severe AD in adults. This prospective real-world case series evaluated the effectiveness and safety of abrocitinib in patients with moderate-to-severe AD who showed an inadequate response to cyclosporine. Nine patients (five females, four males; mean age 19.44 ± 7.68 years, range 10–34 years) were included. Three were adolescents or children in whom abrocitinib was used off-label. The mean disease duration was 13.33 ± 8.06 years, and eight patients had a positive family history of AD. Prior treatments included cyclosporine, methotrexate, and systemic corticosteroids. Abrocitinib was prescribed at a mean dose of 177.77 ± 44.09 mg daily (seven patients received 200 mg, two received 100 mg). Effectiveness was assessed at baseline and weeks 2, 4, 8, and 12 using the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS). Significant and progressive reductions were observed in all scores. Mean EASI decreased from 48.22 ± 7.88 at baseline to 6.33 ± 3.35 at week 12 (P < 0.0001). IGA scores improved from 4 to 1.22 ± 0.44, while PP-NRS declined from 8.44 ± 0.52 to 2 ± 0.86 by week 12, with significance evident early in treatment. Most patients demonstrated good adherence, and dose adjustments were required in some cases. One patient developed mild thrombocytopenia. Abrocitinib demonstrated rapid, significant clinical improvement and was generally well-tolerated, supporting its role as an effective option for moderate-to-severe AD, particularly in patients with inadequate response to cyclosporine.

Introduction

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease marked by intense pruritus, eczematous lesions, and significant impairment in quality of life. Moderate-to-severe cases often necessitate systemic immunomodulatory therapy.[1] Despite the use of conventional systemic agents such as cyclosporine, methotrexate, or corticosteroids, many patients exhibit suboptimal therapeutic responses, intolerance, or disease recurrence upon drug withdrawal. This highlights the urgent need for effective and rapidly acting therapies in cases that are refractory.[2]

Recent advances in the pathophysiological understanding of AD have identified key roles for Janus kinase (JAK)-dependent cytokine signaling in disease propagation.[3] Abrocitinib, an oral selective JAK1 inhibitor, has emerged as a promising therapeutic modality due to its ability to target multiple cytokines involved in AD pathogenesis, including IL-4, IL-13, IL-31, and IFN-γ. Phase III trials have demonstrated its efficacy and safety in adult and adolescent populations, leading to its approval for the treatment of moderate-to-severe AD.[4]

However, real-world data on abrocitinib use in diverse ethnic and age groups, particularly in the Indian population and in patients unresponsive to cyclosporine, remain lacking. Moreover, data regarding off-label use in adolescents and its impact on pruritus severity and the rapidity of clinical improvement in resource-constrained settings are sparse.

Abrocitinib was approved and introduced to the Indian market in late 2023. This study presents a prospective real-world case series evaluating the effectiveness and tolerability of abrocitinib in Indian patients with moderate-to-severe AD who had an inadequate response to cyclosporine. The study provides additional insights into the early onset of action, pruritus reduction, and safety profile of abrocitinib, contributing to the growing body of evidence supporting its use in difficult-to-treat AD cases.

Materials and Methods

Study design and setting

This was a prospective, real-world, case series conducted at a tertiary dermatology centre in eastern India between October 2023 and March 2025. The study included patients with moderate-to-severe AD who demonstrated inadequate response to cyclosporin and were subsequently treated with oral abrocitinib.

Patient selection and management

Adults (≥18 years), adolescents (10 to 19 years), and school-aged children (6 to 14 years) with moderate-to-severe atopic dermatitis, diagnosed according to the Hanifin and Rajka criteria, were included in this study if they had an inadequate response to cyclosporine (4–5 mg/kg/day), defined by an EASI score greater than 21.1 and an IGA score of 4. Patients were excluded if they had a history of active infection, laboratory evidence of latent tuberculosis or hepatitis B or C, or a known immunodeficiency. The diagnosis and severity assessments were confirmed by board-certified dermatologists. Institutional ethical clearance was obtained.

Patients were administered oral abrocitinib at a daily dose of 100 mg or 200 mg, determined by age, clinical severity, patient body weight, and tolerability. No other systemic or biologic therapies were co-administered during the study period. Emollients and topical corticosteroids or calcineurin inhibitors were continued as per standard care.

Clinical assessment and outcome measures

Disease severity and treatment response were evaluated at baseline and at weeks 2, 4, 8, and 12 using validated clinical tools: the Eczema Area and Severity Index (EASI), the Investigator’s Global Assessment (IGA), and the Peak Pruritus Numerical Rating Scale (PP-NRS). These assessments were consistently performed at each time point to monitor efficacy and safety. The primary endpoint was the change in mean EASI score from baseline to week 12. Secondary endpoints included changes in IGA and PP-NRS scores, along with the recording of any adverse events.

Data analysis

Data were analysed using Microsoft Excel and GraphPad Prism. Descriptive statistics were used to summarise demographic and clinical characteristics. Continuous variables were expressed as means ± standard deviation. Paired t-tests were performed to compare changes in EASI, IGA, and PP-NRS scores at each time point relative to baseline. A P-value <0.05 was considered statistically significant.

Results

Baseline characteristics

A total of nine patients (five females and four males) with moderate-to-severe AD were included in the study. The mean age was 19.44 ± 7.68 years (range: 10–34 years), with three patients below the age of 18 years. The mean disease duration was 13.33 ± 8.06 years (range: 6–29 years), and eight patients (88.9%) had a positive family history of AD. All patients had previously received systemic therapy, including cyclosporine, methotrexate, or oral corticosteroids.

The mean daily dose of abrocitinib was 177.77 ± 44.09 mg, with seven patients receiving 200 mg and two patients on 100 mg.

Clinical efficacy

All patients were evaluated at baseline and weeks 2, 4, 8, and 12 using the EASI, IGA, and PP-NRS. Progressive clinical improvement was observed across all parameters throughout the treatment period.

EASI scores declined steadily from a baseline mean of 48.22 ± 7.88 to 35.00 ± 8.81 at week 2, 19.44 ± 8.29 at week 4, 12.44 ± 6.67 at week 8, and 6.33 ± 3.35 at week 12. The reduction in EASI scores was statistically significant as early as week 2 (P = 0.0003), with a highly significant improvement noted by week 12 (P < 0.0001) [Figure 1a].

Figure 1.

(a) Reduction of EASI score in patients of atopic dermatitis on Abrocitinib across 12 weeks. (b) Reduction of IGA score in patients of atopic dermatitis on Abrocitinib across 12 weeks. (c) Reduction of PP-NRS score in patients of atopic dermatitis on Abrocitinib across 12 weeks

Similarly, IGA scores showed marked improvement, decreasing from 4.00 ± 0.00 at baseline to 3.44 ± 0.72 at week 2, 2.33 ± 0.71 at week 4, 1.77 ± 0.44 at week 8, and 1.22 ± 0.44 at week 12. Statistically significant changes were evident from week 4 onwards (P = 0.001 at week 4; P < 0.0001 at week 12) [Figure 1b].

PP-NRS scores, reflecting the severity of pruritus, also showed significant reduction from a mean of 8.44 ± 0.52 at baseline to 4.55 ± 0.88 at week 2, 3.22 ± 0.97 at week 4, 2.33 ± 1.11 at week 8, and 2.00 ± 0.86 at week 12. The decline in pruritus intensity was statistically significant from the first follow-up at week 2 (P < 0.0001) and remained substantial through week 12 (P < 0.0001) [Table 1 and Figure 1c]. Pre- and post-treatment photographs of a patient are shown in Figure 2a and b.

Table 1.

Clinical characteristics and treatment response in patients with moderate-to-severe atopic dermatitis treated with oral abrocitinib

Patient serial number	Age, sex	Duration of disease (years)	Previous medication	Abrocitinib dose (mg)	Baseline (EASI/IGA/PP-NRS)	2 weeks	4 weeks	8 weeks	12 weeks
01	34, M	29	CyA, steroids, MTX	200	58/4/8	44/3/4	18/3/3	14/2/2	6/1/2
02	18, M	12	CyA, steroids	200	48/4/9	41/4/5	26/3/4	19/2/4	8/1/3
03	16, M	8	CyA, steroids	200	53/4/8	36/4/4	13/2/3	7/2/2	4/1/2
04	10, F	7	CyA	100	44/4/9	41/4/6	26/3/4	19/2/3	11/2/3
05	26, F	11	CyA, steroids	200	56/4/8	32/4/4	17/2/3	9/2/2	6/1/2
06	26, F	15	CyA	200	42/4/9	22/2/4	13/2/2	6/1/1	4/1/1
07	11, F	8	CyA, steroids	100	56/4/9	46/4/6	35/3/5	23/2/4	12/2/3
08	25, F	24	CyA, steroids, MTX	200	41/4/8	30/3/4	19/2/3	11/2/2	3/1/1
09	19, M	6	CyA	200	36/4/8	23/3/4	8/1/2	4/1/1	3/1/1

Figure 2.

(a) Pre-treatment photograph of a patient with atopic dermatitis. (b) Post-treatment photograph of a patient with atopic dermatitis

Safety and tolerability

Abrocitinib was generally well tolerated. One patient developed thrombocytopenia with a platelet count of 1,20,000/μL, which did not warrant treatment withdrawal. The dose of abrocitinib was reduced from 200 mg to 100 mg daily with close monitoring. At the subsequent follow-up visit, the platelet count had normalised, and the patient was re-escalated to 200 mg daily without recurrence of thrombocytopenia. Platelet counts were monitored at every follow-up visit (baseline, weeks 2, 4, 8, and 12). No serious adverse events or treatment discontinuations occurred. Treatment adherence was satisfactory in all cases. The patients are still under follow-up, and we plan to prepare a larger dataset in future work.

Discussion

This study presents the first real-world data from the Indian subcontinent on the clinical effectiveness and safety of abrocitinib in patients with moderate-to-severe AD who were refractory to at least one systemic therapy, primarily cyclosporine. Although abrocitinib is approved for use in adults with atopic dermatitis, we included a few children and adolescents in this study on an off-label basis due to the lack of alternative approved treatments in India following the unavailability of dupilumab.

Our results demonstrated a statistically and clinically significant improvement in EASI, IGA, and PP-NRS scores as early as week 2, with continued improvement up to 12 weeks. The mean EASI score decreased by 86.9% over 12 weeks. Pruritus, measured by the PP-NRS, dropped significantly from a mean of 8.44 to 2.00. These results are in line with the JADE MONO-1 and MONO-2 trials, which demonstrated early and dose-dependent responses with abrocitinib monotherapy in adolescents and adults.[4]

In the JADE REGIMEN phase 3 withdrawal study, abrocitinib at both 200 mg and 100 mg doses maintained remission in most patients over 40 weeks. Moreover, treatment responses could be successfully regained upon re-introduction after disease flare. Although our cohort was smaller and less controlled, it similarly showed sustained disease control with both dosing regimens, highlighting the practical feasibility of abrocitinib in real-world settings.[5]

Furthermore, our findings complement and extend previous real-world reports from Europe and Asia. Gargiulo et al.[6] reported that 49.4% of Italian patients achieved EASI-90 at 16 weeks, and 70.6% reported ≥4-point reductions in PP-NRS. Similarly, Olydam et al.[7] noted that abrocitinib achieved significant symptom relief in patients who had failed prior targeted therapies, with a median EASI reduction from 14.7 to 4.0 and NRS itch score from 7.0 to 3.0. Our population, notably younger and with a longer disease duration (mean 13.3 years), achieved comparable or superior outcomes, despite limited therapeutic alternatives and infrastructure constraints in India.

Abrocitinib’s rapid anti-pruritic action is particularly noteworthy. In our cohort, substantial PP-NRS reduction was evident by week 2—a finding echoed in JADE EXTEND and Japanese real-world cohorts. This rapid onset is crucial in contexts where prompt disease control is prioritised, such as in students or professionals facing psychosocial distress, a recurring theme in our clinical rationale for treatment initiation.

In terms of safety, no severe adverse events were observed in our cohort, aligning with prior evidence suggesting a favorable short-term safety profile. One case of mild thrombocytopenia was managed conservatively, consistent with known hematologic AEs reported in the JADE trials and other observational cohorts.[4,5,6,7]

An important distinction in our study is the inclusion of adolescent patients, treated off-label with abrocitinib based on clinical necessity. Our findings corroborate recent pediatric data from China, which demonstrated that age-based dosing of abrocitinib was well tolerated and effective in adolescents, with EASI-75 achieved in over 60% by week 12.[8]

Limitations

This study has several limitations, including the small sample size and lack of a comparator group. Laboratory monitoring and long-term follow-up were not uniformly available across all cases. However, in light of limited Indian data, this study provides critical early insight into the integration of abrocitinib into routine dermatological practice in a resource-constrained setting.

Conclusion

Our findings demonstrate that abrocitinib is an effective and well-tolerated treatment for moderate-to-severe AD in Indian patients, particularly in cases refractory to conventional systemic therapy. Rapid pruritus control, early clinical improvement, and favourable tolerability underscore its value in real-world settings. Further studies with larger cohorts and long-term follow-up are warranted to better define its role in the Indian therapeutic landscape.

Patient consent on file

Consent for the publication of data was obtained by the authors during recruitment.

Legends

Table 1 summarises demographic details, disease duration, prior systemic treatments, abrocitinib dosing, and clinical response as assessed by EASI (Eczema Area and Severity Index), IGA (Investigator’s Global Assessment), and PP-NRS (Peak Pruritus Numerical Rating Scale) scores at baseline and at 2, 4, 8, and 12 weeks of treatment. CyA: Cyclosporine, MTX: Methotrexate.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.