To the Editor: Atopic dermatitis (AD) is a chronic, relapsing inflammatory dermatosis with impairment of skin barrier function and immune dysfunction that affects both children and adults. It is characterized by eczematous lesions, pruritus, sleep disturbance, and diminished quality of life. Management of mild AD relies on emollients, topical corticosteroids, topical calcineurin inhibitors, and phototherapy, while systemic corticosteroids, immunosuppressive agents, and biologics are used for severe refractory cases.[1] Systemic corticosteroids and immunosuppressants have many undesirable side effects. Patients with moderate-to-severe AD who do not respond adequately to topical therapies have few effective treatment options.

Abrocitinib is an oral, highly selective, Janus kinase-1 (JAK1) inhibitor. The JAK-signal transducer and activator of transcription (STAT) signaling pathway mediates several immune pathways underlying AD. It is also thought to impact various downstream inflammatory cytokines, including interleukin (IL)-4, IL-13, IL-22, IL-31, thymic stromal lymphopoietin (TSLP), and other cytokines involved in the pathogenesis of AD. It has been reported that JAK1 inhibitor abrocitinib is less likely to stimulate an immunogenic response.[2] Phase 2 and phase 3 trials have shown that abrocitinib revealed a good result for the treatment of moderate-to-severe AD. On April 2022, abrocitinib was approved in China for the treatment of moderate-to-severe AD in adults and adolescents older than 12 years who are candidates for systemic therapy.[3] However, the data on the real-life effectiveness of abrocitinib were still limited. This study aimed to determine the real-life effectiveness and safety of abrocitinib treatment in adult patients with AD. The study was approved by the Institutional Ethics Committee of Peking University People's Hospital (No. 2021PHB076-001). Written informed consent was obtained from all patients.

The demographic and clinical data of 21 adult AD patients treated with abrocitinib 100 mg/day for at least 2 weeks were analyzed in our research. All patients satisfied the criteria of Hanifin and Rajka and Chinese criteria for AD. The severity of AD was determined by the eczema area and severity index (EASI) score. Before treatment, all patients underwent screening for the presence of hepatitis B virus (HBV) and tuberculosis (TB) by antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT). Patients with active TB and HBV were excluded. The baseline demographic and clinical characteristics of the patients are shown in Table 1. The mean age of the patients was 46.8 ± 16.1 years including 11 men and 10 women, with an average duration of 10.4 ± 14.4 years. Clinical manifestations of AD occurred before the age of 18 years in four patients (19%). Eleven patients (52%) presented with a personal history of atopic diseases including asthma, allergic rhinitis, allergic conjunctivitis, or urticaria; and ten patients (48%) had a family history of atopic diseases. Before enrollment, all the patients had received at least one systemic treatment for AD. Fifteen (71%) patients had been treated with systemic antihistamines, seven (33%) patients with dupilumab, two (10%) with systemic corticosteroids, two (10%) with systemic cyclosporin A, one (5%) with upadacitinib, and one (5%) with baricitinib.

Table 1 - Baseline clinical characteristics and treatment response of the overall study population (n = 21). Characteristics Results Age (years) 46.8 ± 16.1 Duration of disease (years) 10.4 ± 14.4 Gender Female 10 (48) Male 11 (52) Onset of disease Adult-onset 17 (81) Childhood-onset 4 (19) Atopic comorbidities None 10 (48) Allergic rhinitis 10 (48) Asthma 4 (19) Allergic conjunctivitis 1 (5) Urticaria 5 (24) Systemic comorbidities None 14 (67) Hypertension 4 (19) Diabetes 1 (5) Coronary heart disease 2 (10) AD severity Mild 5 (24) Moderate 6 (29) Severe 10 (48) Previous treatments Topical corticosteroids 19 (91) Topical calcineurin inhibitor 2 (10) Systemic antihistamines 15 (71) Systemic corticosteroids 2 (10) Systemic immunosuppressant 2 (10) Dupilumab 7 (33) Upadacitinib 1 (5) Baricitinib 1 (5) Family history of atopic diseases 10 (48) History of drug allergy 2 (10) Duration of treatment (months) 2.1 ± 1.5 Time to onset of abrocitinib (days) 3.7 ± 2.2 Treatment effectiveness EASI* Pre-treatment 20.8 ± 17.0 Post-treatment 5.5 ± 10.5 NRS* Pre-treatment 7.3 ± 2.7 Post-treatment 2.3 ± 1.9 Adverse event None 13 (62) Headache 2 (10) Nausea 2 (10) Dizziness 3 (14) Acne/folliculitis 5 (24) Abdominal pain 2 (10) Nasopharyngitis 0 (0) Herpes simplex 0 (0) Final treatment status at the time of data lock Under treatment 9 (43) Discontinued due to remission 8 (38) Discontinued due to ineffectiveness 4 (19)

Data are expressed as mean ± standard deviation or n (%). *P <0.001, Post-treatment versus Pre-treatment. AD: Atopic dermatitis; EASI: Eczema area and severity index; NRS: Numerical rating scale.

The treatment courses of patients are also shown in Table 1. All patients received 100 mg of abrocitinib daily. The mean duration of treatment courses was 2.1 ± 1.5 months with an average onset-time of 3.7 ± 2.2 days. Baseline and post-treatment EASI and pruritus numerical rating scale (P-NRS, 0–10) scores were compared. A significant reduction of EASI score (from 20.8 ± 17.0 to 5.5 ± 10.5, P <0.001) and P-NRS (from 7.3 ± 2.7 to 2.3 ± 1.9, P <0.001) was found compared to baseline. At week 2, EASI50, EASI75, and EASI90 responses were achieved in 18 (18/21, 86%), 13 (13/21, 62%), and 7 (7/21, 33%) patients. At week 8, EASI50, EASI75, and EASI90 responses were achieved in 12 (12/13, 92%), 10 (10/13, 77%), and 6 (6/13, 46%) patients. At week 12, the EASI50, EASI75, and EASI90 responses were achieved in 9 (9/9, 100%), 8 (8/9, 89%), and 5 (5/9, 56%) patients, respectively. Eight patients (38%) experienced at least one adverse effect including headache, nausea, dizziness, acne, and abdominal pain. However, serious adverse event was not found. The most common adverse event was acne/folliculitis (5/21, 24%), followed by dizziness (3/21, 14%), headache (2/21, 10%), nausea (2/21, 10%), and abdominal pain (2/21, 10%). Eight patients (38%) discontinued the treatment due to remission and four patients (19%) discontinued due to ineffectiveness.

This study showed that 100 mg of abrocitinib was effective for AD. In addition to significant improvements of the lesions, significant improvements in pruritus were also achieved. These data were consistent with those observed in the randomized clinical trials (RCTs). It has been reported that significant reductions in pruritus scores and EASI scores were reported at week 12 in the treatment groups receiving 100 mg abrocitinib.[4] In this study, EASI50, EASI75, and EASI90 responses were observed in 100%, 88.9%, and 55.6% of patients, similar to the findings in RCTs.

In our research, adverse events were found in eight (8/21, 38%) of the patients. The most common adverse events of abrocitinib were acne/folliculitis (5/21, 24%), dizziness (3/21, 14%), headache (2/21, 10%), nausea (2/21, 10%), and abdominal pain (2/21, 10%), which were more frequent compared to reported RCTs. Nasopharyngitis and upper respiratory tract infection were not observed in our research. In the phase III placebo-controlled cohort, adverse events occurred in 61.0% of AD patients. The most frequent adverse events of abrocitinib 100 mg group in clinical trials were nasopharyngitis (75/608, 12%), upper respiratory tract infection (40/608, 7%), nausea (37/608, 6%), and headache (36/608, 6%). Most adverse events were generally self-limited and seldom required interruption or permanent discontinuation of treatment.[5] The data in our research were different from the results in RCTs. It can be assumed that the relatively high incidence of the adverse events in our research might be due to the small sample size and the short-term following up. Nonetheless, abrocitinib was overall well-tolerated and none of the adverse effects led to drug discontinuation.

In conclusion, our study results suggested that abrocitinib orally 100 mg was efficacious and well-tolerated in AD patients with a favorable benefit-risk profile. A long-term extension study with a larger sample size is still needed. Future analyses and additional data will provide further information on the long-term safety profile of abrocitinib.

Acknowledgments

None.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 82103711) and the Peking University People's Hospital Research and Development Foundation (No. RDY2021-18).

Conflicts of interest

None.

References 1. Fishbein AB, Silverberg JI, Wilson EJ, Ong PY. Update on atopic dermatitis: Diagnosis, severity assessment, and treatment selection. J Allergy Clin Immunol Pract 2020;8: 91–101. doi: 10.1016/j.jaip.2019.06.044. 2. Chen M, Dai SM. A novel treatment for psoriatic arthritis: Janus kinase inhibitors. Chin Med J 2020;133: 959–967. doi: 10.1097/cm9.0000000000000711. 3. Deeks ED, Duggan S. Abrocitinib: First approval. Drugs 2021;81: 2149–2157. doi: 10.1007/s40265-021-01638-3. 4. Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of oral Janus kinase 1 inhibitor abrocitinib for patients with atopic dermatitis: A phase 2 randomized clinical trial. JAMA Dermatol 2019;155: 1371–1379. doi: 10.1001/jamadermatol.2019.2855. 5. Simpson EL, Silverberg JI, Nosbaum A, Winthrop KL, Guttman-Yassky E, Hoffmeister KM, et al. Integrated safety analysis of abrocitinib for the treatment of moderate-to-severe atopic dermatitis from the phase II and phase III clinical trial program. Am J Clin Dermatol 2021;22: 693–707. doi: 10.1007/s40257-021-00618-3.