Dear Editor,
Upadacitinib and abrocitinib are selective, small-molecule Janus kinase 1 (JAK1) inhibitors approved in China for the treatment of moderate-to-severe atopic dermatitis (AD) [
1]. The favorable efficacy and tolerable safety of upadacitinib and abrocitinib have been determined in several clinical trials [
2–5]. However, real-world data, especially in Asian populations, are scant. Therefore, we conducted a prospective, 24-week, real-life observational study to assess the effectiveness and safety of abrocitinib and upadacitinib for the treatment of moderate-to-severe AD in a Chinese patient cohort.
Ninety patients with moderate-to-severe AD (IGA score 3–4) in the Department of Dermatology, Xiangya Hospital, were recruited from June 2022 to June 2023. All patients were diagnosed in accordance with Hanifin and Rajka diagnostic criteria and signed informed consent forms. The patients had an inadequate response or contraindications to conventional systemic therapies, an inadequate response to topical medications for at least four weeks, or experienced an adverse event (AE) in relation to previous systemic therapies. Fifty-one patients were treated with oral abrocitinib (100 mg once daily), and 39 were treated with oral upadacitinib (15 mg once daily). All patients were required to use emollients daily throughout the research and were permitted to continue to use low- or medium-potency topical corticosteroids, calcineurin inhibitors, or phosphodiesterase 4 inhibitor. No concomitant systemic treatment was applied to either group, and previous systemic treatment was discontinued for at least four weeks before enrollment.
The demographic and clinical characteristics of the patients were assessed at the baseline. Disease severity and quality of life scores, including those obtained with the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Scoring Atopic Dermatitis (SCORAD), Dermatology Life Quality Index (DLQI, for patients ≥ 16 years) or Children’s DLQI (CDLQI, for patients aged 12–16 years), Peak Pruritus Numerical Rating Scale (PP-NRS), and Patient-oriented Eczema Measure (POEM), were recorded at the baseline and 2, 4, 16, and 24 weeks after the initial dose. Total serum immunoglobulin (Ig) E and total eosinophil count (TEC) were also analyzed.
The baseline demographic and clinical characteristics of the patients are shown in Tab.1. The proportion of males (56.86% in the abrocitinib group and 66.67% in the upadacitinib group) was slightly larger than that of females. On the basis of the indications of the two JAK1 inhibitors approved in China, the patients treated with abrocitinib in this study were all adults, and those treated with upadacitinib included 17 adolescents and 22 adults.
Representative images of the patients at the baseline and after four weeks of treatment with either abrocitinib or upadacitinib are given in Fig.1, which shows remarkable skin clearance. After treatment with either abrocitinib or upadacitinib, the patients’ IGA, SCORAD, EASI, PP-NRS, POEM, DLQI, and CDLQI scores were considerably reduced in as early as Week 2 and persisted until Week 24 (Fig.1 and 1C). The patients that achieved EASI-75, EASI-90, IGA0/1, and PP-NRS4 after four weeks of treatment with abrocitinib (48.94%, 25.53%, 29.79%, and 55.32%, respectively) or upadacitinib (55.26%, 28.95%, 31.58%, and 57.89%, respectively) showed a rapid response. At 24 weeks of treatment, 75%, 43.75%, and 59.38% of the patients in the abrocitinib group and 73.08%, 53.85%, and 65.38% of the patients in the upadacitinib group achieved EASI-75, EASI-90, and PP-NRS4, respectively (Fig.1). These results indicate that the efficacy of the two JAK1 inhibitors may be sustained for at least 24 weeks. Furthermore, at Week 4, the total serum IgE level decreased considerably from the baseline in the abrocitinib group, and TEC decreased remarkably from the baseline in the abrocitinib and upadacitinib groups (Fig.1). After eliminating the effects of confounding variables (e.g., age and age of onset) via logistic regression analyses, we did not find a statistical difference in the percentages of EASI-75, EASI-90, IGA 0/1, and PP-NRS4 between the two treatment groups (Fig. S1). However, these results should be interpreted with caution because the sample size in each group was insufficient to compare the difference in efficacy between the two groups via sample size calculation. Further studies are needed to clarify the difference in efficacy between the two JAK1 inhibitors.
During the 24-week treatment period, 27.45% (14/51) of the abrocitinib- and 30.77% (12/39) of upadacitinib-treated patients reported at least one AE, but no serious AE was recorded, and no patient discontinued drug use or died due to AEs. The most common AE in both groups was acne, which occurred in 11.76% (6/51) of the abrocitinib-treated patients and 15.38% (6/39) of the upadacitinib-treated patients (Table S1). The rate of acne in our study is consistent with those in previous clinical trials on upadacitinib but higher than those in other studies on abrocitinib [
3–
5]. All acne events in our patient cohort were mild and improved with symptomatic treatment.
In this study, we demonstrated that abrocitinib and upadacitinib considerably improved lesions and relieved pruritus in Chinese patients with moderate-to-severe AD in as early as Week 2, and the favorable effect was sustained for at least 24 weeks. The effectiveness observed in our study is consistent with that found in previous clinical trials [
3–
5]. Recently, several real-world studies on abrocitinib or upadacitinib have been published. In a study of 41 patients treated by abrocitinib for 28 weeks in the Netherlands, the percentages of EASI-75 and IGA0/1 were 31.7% and 22%, respectively [
6]. The percentage of EASI-75 at Week 16 in the upadacitinib-treated group in our study is similar to that reported in a study of 17 Spanish patients (74.2% vs. 76.5%), but the percentage of EASI-90 in our study is lower than that in the Spanish study (38.7% vs. 52.9%) [
7]. In addition, the percentage of EASI-75 at Week 16 in our upadacitinib-treated patients is lower than that reported in another study of 71 Italian patients (74.2% vs. 85.7%) [
8]. The discrepancy in these reports may be partially due to the sample size used, drug dosage, population, and heterogeneity of the AD phenotype [
9]. A published real-world study on upadacitinib in the Asian population was conducted in Japan; the EASI-75 proportion at Week 4 (51.6%) is similar to that in our study (55.3%) [
10]. However, this real-world study on the effectiveness and safety of abrocitinib and upadacitinib in the Asian population had a long term and large sample size.
This study has some limitations. First, it is a single-center, open label, hospital-based study and may have selective bias. Second, the sample size was limited. Third, the follow-up time was only 24 weeks. Fourth, only low doses of the two JAK1 inhibitors were used. The instructions for the two JAK1 inhibitors approved in China recommend the use of a low initial dose, and the dose can only be increased when the response is insufficient. Last, the age distribution between the two treatment groups differed considerably because of the different age indications for the two JAK1 inhibitors approved in China and the limited sample size. Therefore, long-term follow-up studies with a multi-center approach, a large number of patients, and different drug doses are needed.
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