Efficacy and safety of abrocitinib in Chinese patients with moderate-to-severe atopic dermatitis: A post hoc analysis of the JADE REGIMEN phase 3 trial

To the Editor: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a relapsing-remitting disease course that warrants flexible dosing.[1,2] In China, abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is approved at a 100 mg starting dose for adults with refractory moderate-to-severe AD who did not inadequately respond to other systemic therapies (i.e., corticosteroids or biologics), or for whom these treatments are not advisable. If the response achieved with abrocitinib 100 mg is inadequate, 200 mg dosing can be considered, which could be administered as a short-term treatment (≤12 weeks).[3] The phase 3 JADE REGIMEN trial (Clinicaltrials.gov, NCT03627767) evaluated maintenance of response with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg), or drug withdrawal (placebo) in patients with moderate-to-severe AD who responded to abrocitinib induction therapy.[4] Here, we aimed to characterize the efficacy and safety of abrocitinib in the Chinese patient subgroup within JADE REGIMEN. This post hoc analysis included patients from the mainland of China who enrolled in JADE REGIMEN. Details of the JADE REGIMEN study design have been previously published.[4] Briefly, eligible patients were aged ≥12 years with moderate-to-severe AD (Investigator's Global Assessment [IGA] score ≥3, Eczema Area and Severity Index [EASI] ≥16, ≥10% body surface area affected, Peak Pruritus Numerical Rating Scale [PP-NRS, used with permission of Regeneron Pharmaceuticals, Inc., and Sanofi] score ≥4). Patients who responded (IGA score of 0 [clear] or 1 [almost clear] with ≥2-grade improvement, and ≥75% improvement from baseline in EASI [EASI-75]) to abrocitinib 200 mg in a 12-week open-label induction period were randomly assigned to receive abrocitinib 200 mg, abrocitinib 100 mg, or placebo in a 40-week maintenance period. Patients who experienced protocol-defined flare (≥50% loss of the initial EASI response at Week 12 of the induction period and an IGA score ≥2 during the maintenance period) entered a 12-week rescue period and received abrocitinib 200 mg plus medicated topical therapy. This analysis assessed the proportion of patients experiencing flare during the maintenance period across the three treatment arms and the proportion of patients achieving IGA 0/1, EASI-75, and ≥4-point improvement from baseline in PP-NRS (PP-NRS4) during the induction, maintenance, and rescue periods. Safety was assessed by treatment-emergent adverse event (TEAE) monitoring. JADE REGIMEN was conducted in agreement with ethical principles from the Declaration of Helsinki and all International Council for Harmonisation Good Clinical Practice Guidelines and was approved by institutional review boards or ethics committees at each site, and internal and external review committees monitored the safety of patients throughout the study. All patients provided written informed consent. Further details on the methodology are provided in the Supplementary file [https://links.lww.com/CM9/C24]. Of 1233 patients who received induction, 118 (9.6%) were enrolled from the mainland of China. Patient demographics and baseline disease characteristics were generally comparable between the China subgroup and the overall study population,[4] although disease duration was shorter, and a greater proportion had severe disease in the China subgroup [Supplementary Table 1, https://links.lww.com/CM9/C24]. In the China subgroup, median disease duration was lower in the placebo maintenance arm compared with the abrocitinib arms, but with largely overlapping interquartile ranges [Supplementary Table 1, https://links.lww.com/CM9/C24]. The proportion of patients responding to induction was similar in the China subgroup (69.5% [82/118]) and the overall study population (65.2% [800/1227]).[4] At the end of maintenance (study week 52), 21/29 (72.4%), 17/31 (54.8%), and 2/19 (10.5%) patients in the China subgroup achieved EASI-75 with abrocitinib 200 mg, 100 mg, and placebo, respectively, compared with 169/257 (65.8%), 120/258 (46.5%), and 37/264 (14.0%) patients in the overall study population;[4] similar responses were observed for IGA 0/1 and PP-NRS4 [and Supplementary Table 2, https://links.lww.com/CM9/C24]. The probability of flare in the China subgroup was 13.8%, 41.5%, and 76.0% with abrocitinib 200 mg, 100 mg, and placebo, respectively, and was comparable to the overall study population.[4] The Kaplan–Meier estimate of median time to flare was 28.5 days (95% confidence interval [CI], 22.0−119.0) in the placebo arm and was not reached in either abrocitinib arm in the China subgroup; comparable findings were observed in the overall study population.[4] The majority of patients recaptured an EASI-75 response at Week 12 of rescue therapy in both the China subgroup (75.0% [21/28]) and the overall study population (82.2% [278/338]; Supplementary Table 3, https://links.lww.com/CM9/C24).[4] During the maintenance period, TEAEs were reported in 25/29 (86.2%), 23/32 (71.9%), and 8/20 (40.0%) patients in the abrocitinib 200 mg, 100 mg, and placebo arms of the China subgroup, respectively [Supplementary Table 4, https://links.lww.com/CM9/C24]. TEAEs were mainly mild or moderate in severity. Compared with the overall study population,[4] the rates of overall TEAEs were higher in the China subgroup across all study periods, and the rates of serious or severe TEAEs were generally lower [Supplementary Table 4, https://links.lww.com/CM9/C24]. One Chinese patient, aged 34 years, had a serious infection (pneumonia; incidence rate [IR], 3.38/100 patient-years [95% CI, 0.09−18.84]) during the induction period. Herpes zoster events were reported in two Chinese patients in the abrocitinib 200-mg arm during the maintenance period (IR, 9.21/100 patient-years [95% CI, 1.12−33.26]). No events of non-melanoma skin cancer, tuberculosis, or adjudicated malignancies or cardiovascular events were reported during the entirety of the study period in the China subgroup. No deaths occurred in the China subgroup during the study. In this post hoc analysis of Chinese patients from JADE REGIMEN, 70% of patients responded to induction therapy with abrocitinib 200 mg, and the response was maintained over 40 weeks in >58% of abrocitinib-treated patients. Of those patients who experienced disease flare, 75% had an EASI-75 response with abrocitinib 200 mg plus medicated topical therapy. Overall, responses to abrocitinib induction, maintenance, and rescue treatment were comparable between the China subgroup and the overall study population.[4] Regarding safety, abrocitinib was well-tolerated in the China subgroup, and no new safety signals were observed compared with the overall study population. This study was limited due to the post hoc nature of the analysis and was not powered to detect statistical significance or to control type I error. Interpretation of treatment differences between abrocitinib and placebo is limited due to the small sample size of the China subgroup. Together, these results indicate that an initial 12-week exposure to abrocitinib 200 mg before maintenance therapy with abrocitinib 100 mg or 200 mg may be an effective and well-tolerated treatment strategy for patients with moderate-to-severe AD in China. Acknowledgments Editorial and writing support was provided by ApotheCom under the direction of authors, and in accordance guidelines from the American Medical Writers Association, European Medical Writers Association, and International Society for Medical Publication Professionals, and was funded by Pfizer Inc., New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med. 2022; 10.7326/M22-1460). Conflicts of interest Gerardo A. Encinas, Bo Wang, Xin Luo and Shiqi Li are employees of Pfizer Inc. and hold stock and/or stock options. Shefali Vyas was an employee of Pfizer Inc. at the time the study was conducted.