ABSTRACT
Objective
The aim of this study is to evaluate the effectiveness and safety of JAK inhibitors in patients with moderate to severe atopic dermatitis by performing a systematic review and meta‐analysis using data from studies in real‐world settings.
Design
Systematic review and meta‐analysis. Pooled estimates for effectiveness and safety were assessed using the Freeman–Tukey Double ArcSine method. Statistical heterogeneity was assessed using I 2 statistics. A random‐effects model (DerSimonian‐Laird method) was applied to consider the heterogeneity within and between studies and to give a more conservative estimate. The study quality assessment tools developed by the National Heart, Lung, and Blood Institute were used.
Data Source
Relevant studies were searched in March 2025 using four databases: PubMed, Embase, Scopus, and Web of Science.
Eligibility Criteria
Studies evaluating the effectiveness or safety of systemic JAK inhibitors among patients with moderate to severe atopic dermatitis in a real‐world setting were included.
Results
A total of 50 studies were included in this review. Regarding their effectiveness, the pooled estimates with a 95% CI of Eczema Area and Severity Index (EASI)‐75 were 44% (34%–55%), 45% (28%–62%), 59% (51%–66%), 73% (64%–81%), 70% (57%–81%), and 86% (72%–96%) at 4, 8, 12, 16, 24, and 52 weeks. For safety, the most common adverse events were acne (16%), followed by increased creatine phosphokinase levels (13%) and increased lipids (12%).
Conclusion
Our meta‐analysis of JAK inhibitors in patients with atopic dermatitis demonstrated that the overall outcomes from real‐world settings are comparable to those from clinical trials.
Systematic Review Registration
Protocol Registration: PROSPERO CRD42024569258.
Keywords: abrocitinib, atopic dermatitis, baricitinib, Janus kinase inhibitors, real‐world data, upadacitinib
This systematic review and meta‐analysis of 50 cohort studies summarises the real‐world effectiveness and safety of systemic JAK inhibitors for the treatment of moderate to severe atopic dermatitis.
Summary.
This study provides quantitative evidence of real‐world outcomes of systemic JAK inhibitors.
JAK inhibitors demonstrated a significant improvement in EASI, achieving an EASI‐75 of 86% at 52 weeks.
The most common adverse events were acne, increased creatine phosphokinase levels, and increased lipids.
1. Introduction
Atopic dermatitis is a chronic inflammatory skin disease with symptoms such as pruritus, rash, and dry skin [1, 2, 3]. It usually develops in infancy and early childhood, then continues throughout adulthood [4]. Over the past decade, the understanding of its pathophysiology has significantly advanced, highlighting the role of various cytokines, including interleukin (IL)‐4, IL‐13, IL‐22, IL‐31, and interferon‐γ, signalling through the Janus kinase (JAK)‐signal transducer and activation of transcription (STAT) pathway, allowing the development of targeted therapy [5, 6].
JAK inhibitors block the signalling of inflammatory cytokines through the JAK–STAT pathway, thereby suppressing pro‐inflammatory responses. They are now used in different inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel diseases [3, 5]. Recently, systemic JAK inhibitors have been approved for the treatment of atopic dermatitis, including abrocitinib (JAK1‐selective), baricitinib (JAK1/2‐selective), and upadacitinib (JAK1‐selective).
With promising results in randomised controlled trials (RCTs), systemic JAK inhibitors are emerging as an effective treatment option for atopic dermatitis [7, 8]. However, the effectiveness and safety of these interventions in diverse patient populations warrant further investigation through real‐world studies, as existing research is limited and often based on small sample sizes. Although an RCT is the strongest study design in clinical research to reliably and accurately assess a drug's efficacy in well‐defined randomised groups based on protocols [9], real‐world data (RWD) have the advantage to provide evidence of a drug's effectiveness and safety in various heterogeneous populations during a longer time frame without strict protocols [10]. However, to the best of our knowledge, no systematic review has been conducted on the real‐world data regarding the effectiveness and safety of JAK inhibitors in patients with atopic dermatitis. The aim of this study is to evaluate the effectiveness and safety of systemic JAK inhibitors as a treatment of moderate to severe atopic dermatitis in order to provide clear real‐world evidence based on a systematic review and meta‐analysis of RWD.
2. Methods
2.1. Data Sources and Search Strategy
The study protocol was registered on PROSPERO (CRD42024569258) [11]. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) [12] and was reported in accordance with the Meta‐analysis of Observational Studies in Epidemiology (MOOSE) guidelines and checklists [13].
A literature search was conducted on March 24th, 2025 using four databases: PubMed, Embase, Scopus, and Web of Science. The following search strategy was used: #1 (‘atopic dermatitis’ or ‘atopic eczema’) and #2 (‘janus kinase inhibitor*’ or ‘JAK inhibitor*’ or abrocitinib or cibinqo or baricitinib or olumiant or upadacitinib or rinvoq). There was no restriction on language or publication date.
2.2. Inclusion and Exclusion Criteria
After removing duplicates, two authors (YK and JY) screened titles and abstracts for inclusion. Then, full‐texts were retrieved and assessed for eligibility by the same two authors based on predefined criteria. Any disagreements were resolved by consensus among them.
Studies were selected if they evaluated the effectiveness or safety of systemic JAK inhibitors, specifically abrocitinib, baricitinib, and upadacitinib, among patients diagnosed with moderate to severe atopic dermatitis, in a real‐world setting. No restrictions were imposed regarding pre‐treatments or concomitant therapies. Studies were excluded if they (1) were not original studies; (2) were not conducted in real‐world settings (e.g., RCTs); (3) included only children; or (4) included less than 10 patients. The cutoff of 10 was chosen to ensure adequate statistical power and to avoid instability from small sample sizes based on previous literature [14, 15]. If there were overlapping studies, the most recent or most comprehensive study was included.
2.3. Data Extraction and Assessment of Study Quality
The following data was extracted by three authors (YK, GS, and JY): first author, publication year, study design, number of patients, study period, study country, follow‐up length, study population, mean or median age, percentage of men, studied drugs, concomitant therapies, baseline Eczema Area and Severity Index (EASI).
To access treatment outcomes, the Core Outcome Sets recommended by the Harmonising Outcome Measures for Eczema were extracted, including EASI for clinical signs, Numerical Rating Scale (NRS) and Patient‐oriented Eczema Measure (POEM) for patient‐reported symptoms, Atopic Dermatitis Control Tool (ADCT) for long‐term control, and Dermatology Life Quality Index (DLQI) for quality of life [16]. The primary outcome of effectiveness was evaluated by extracting the patients achieving EASI50, EASI75, and EASI90. The EASI assesses the extent of the disease on a scale of 0 to 6 and four signs of diseases (i.e., erythema, edema, excoriation, and lichenification) on a scale of 0 to 3 across four body regions (i.e., head and neck, upper extremities, trunk, and lower extremities), with a total score ranging from 0 to 72 [17]. EASI50, EASI75, and EASI90 refer to the proportions of patients whose EASI score improved by more than 50%, 75%, or 90%, respectively, from baseline during the follow‐up period. EASI50, which indicates a clinically meaningful improvement, corresponds to an approximately 1‐grade improvement in the physical global assessment (PGA) or investigator global assessment (IGA), meeting the minimal important change for patients with moderate to severe atopic dermatitis [18, 19]. EASI75 reflects a 2‐grade improvement in PGA or IGA, whereas EASI90 corresponds to clear or almost clear, with a ≥ 2‐grade improvement in PGA or IGA. The secondary outcomes were the percentage change in EASI and the mean differences in NRS, POEM, ADCT, and DLQI scores from baseline during the follow‐up period. The NRS is a single‐item, patient‐reported outcome used to assess the severity of the symptoms in atopic dermatitis, including pruritus, skin pain, and sleep disturbance [20, 21]. In this study, we included only the pruritus NRS, regardless of the assessment period (e.g., past 24 h or past week), and excluded average scores to maintain consistency across studies. For safety outcomes, the numbers of reported adverse events and the total number of patients were extracted to calculate the proportions. Serious adverse events, including serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, were extracted and described separately.
For the binary variables, we extracted the number of patients. For continuous variables, we extracted means and standard deviations. When studies reported only medians, interquartile ranges, or ranges, we estimated the means and standard deviations using the formulas proposed by Wan et al. [22] Graph data were extracted using Engauge Digitizer version 12.1.
To minimise bias and evaluate the quality of the studies included in this review, study quality was assessed using the ‘Quality Assessment Tool for Before‐After (Pre‐Post) Studies with No Control Group’ developed by the National Heart, Lung, and Blood Institute [23]. This tool aligns with the design of our research, as it is specifically intended for studies that assess outcomes before and after an intervention in a single group, without a control group for comparison. Study quality was assessed using 12 items and classified as good (≥ 75%), fair (25%–74%), or poor (< 25%). The quality assessment was independently conducted by two authors (YK and JY), and any discrepancies were resolved through discussion.
2.4. Statistical Analysis
The effectiveness and safety outcomes were reported as proportions with 95% confidence intervals (CI). The proportions were transformed via the Freeman–Tukey Double ArcSine method. Meta‐analysis was performed only when five or more studies reported the same outcome, without zero‐event studies. Statistical heterogeneity was assessed using I 2 statistics. A random‐effects model (DerSimonian‐Laird method) was applied to consider the heterogeneity within and between studies and to give a more conservative estimate. Forest plots were used to present the findings. Funnel plots and Begg's tests were used to assess the presence of publication bias [24]. Subgroup analysis was performed by type of JAK inhibitor (i.e., abrocitinib, baricitinib, upadacitinib). Sensitivity analyses were conducted by restricting the analysis to prospective studies or those rated as good quality. All statistical analyses were performed using R software (version 4.4.1) with ‘meta’ package [25].
3. Results
The study selection process is summarised in Figure 1. In total, 6826 studies were identified from the four databases and 4047 duplicates were removed. After excluding 2533 irrelevant studies based on their titles and abstracts, 246 studies were assessed for eligibility, of which 196 studies were excluded (Table S1). Finally, a total of 50 studies were included in this study [26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75].
FIGURE 1.
Flow diagram of study selection.
Of the included studies, 21 were multi‐centre cohort studies and 29 were single‐centre cohort studies (Table 1). A total of 26 studies were from Europe, 19 were from the Western Pacific and five were from America. The average age ranged between 18 and 51 years, except for one study conducted in an older population [32]. The proportion of males ranged between 34% and 92%. The average baseline EASI ranged between 11 and 33. Although several studies did not report this, approximately two‐thirds allowed the use of topical agents, with one allowing systemic corticosteroids for bridging therapy and the other for exacerbation. Of the funding sources, 20 studies reported no funding, 10 were publicly funded, nine were industry‐funded, one was funded by both, and nine did not report their funding source. Regarding study quality, 24 studies were rated as good and 26 as fair.
TABLE 1.
Baseline characteristics of the included studies.
| First author (year) | Type of study | Study period | Nation | Study population | Follow‐up (Weeks) | Sample size | Age a | Male (%) | Baseline EASI a | Previous biologics or JAK inhibitors (%) | Allowed concomitant treatment | Studied drugs | Funding source | Study quality |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Armario‐Hita (2024) | Prospective multi‐centre | From May 2023 to Mar 2024 | Spain | EASI > 21 and failure to cyclosporine | 24 | 76 | 33.9 ± 12.2 | 44 (57.9) | 21.8 ± 9.6 | Dupilumab (43.4), tralokinumab (27.6), Upadacitinib (22.3), Baricitinib (10.5) | AH, TCS | A | None | Good |
| Bai (2024) | Retrospective single centre | From Apr 2022 to Feb 2023 | China | Fulfilled the William diagnostic criteria | 12 | 16 | 41.9 ± 18.0 | 8 (50.0) | 22.5 ± 5.4 | Dupilumab (18.8), Baricitinib (6.3) | No restriction | A | N/A | Fair |
| Boesjes (2022) | Prospective multi‐centre | From Jan 2021 to Feb 2022 | Netherlands | Fulfilled the criteria for Baricitinib treatment by the Dutch Society of Dermatology and Venerology | 16 | 51 | 39.5 ± 15.5 | 34 (66.7) | 18.3 ± 13.5 | Dupilumab (74.5), Abrocitinib (3.9) | Systemic treatment to be discontinued prior to initiation, if possible | B | Private | Good |
| Boesjes (2023) | Prospective multi‐centre | From Oct 2021 to May 2022 | Netherlands | Failure to systemic treatment | 16 | 47 | 33 (26.0–43.0) | 31 (66.0) | 16.6 (N/A) | Dupilumab (93.6), tralokinumab (2.1) | TCS | U | Private | Good |
| Chen (2024) | Prospective single centre | From Jun 2022 to Jun 2023 | China | IGA ≥ 3 | 24 | A: 51 | 39.7 ± 18.0 | 29 (56.7) | 17.9 ± 11.7 | Dupilumab (21.6) | TCS, TCI, topical PDE4i | A, U | Public | Good |
| U: 39 | 28.2 ± 17.9 | 26 (66.7) | 19.2 ± 13.3 | Dupilumab (30.8) | ||||||||||
| Cho (2024) | Single centre | N/A | Taiwan | Poor response to topical treatments | 16 | 28 | 26.1 ± 6.4 | 20 (71.4) | 33.1 ± 8.9 | N/A | N/A | B | Public | Fair |
| Dasilva (2025) | Retrospective multi‐centre | N/A | US | Failure to systemic treatment | 16–120 | 38 | 72.9 ± 7.9 | 17 (44.7) | N/A | Dupillumab or tralokinumab (52.6) | N/A | U | None | Fair |
| De Greef (2023a) | Retrospective single centre | From July 2021 to August 2022 | Belgium | Failure to systemic treatment | Median: 54.4 | 29 | 37.0 (± 37.0) | 20 (69.0) | 22.4 ± 4.4 | Dupilumab (34.5), Baricitinib (24.1), tralokinumab (10.3), nemolizumab (6.9) | N/A | U | None | Fair |
| De Greef (2023b) | Retrospective single centre | From Jan 2021 to May 2023 | Belgium | Failure to systemic treatment | Median: 54.4 | 19 | 39 (± 29) | 14 (73.7) | N/A | Dupilumab (5.3) | TCS, TCI | B | None | Good |
| De Wijs (2022) | Prospective single centre | Between Dec 2020 and Jun 2021 | Netherlands | Failure to dupilumab | 12 | 25 | 29 (24–51) | 16 (64.0) | 12.8 (10.0–25.0) | Dupilumab (100.0) | TCS, TCI, bridging therapy with systemic corticosteroids | B | None | Good |
| Feraru (2022) | Multi‐centre | From Jul 2020 to Nov 2021 | Israel | IGA ≥ 3, failure to topical and systemic treatment | Mean: 33 | 12 | 51.3 (27–85) | 9 (75.0) | NA | Dupilumab (91.6) | Topical treatment | U | Private | Fair |
| Fomina (2024) | Single centre | From Jan 2022 to Jul 2022 | Russia | EASI ≥ 7, SCORAD ≥ 25, IGA ≥ 3, and failure to TCS and/or TCI | 16 | 19 | 33 [19–46] | 8 (42.1) | 29.5 ± 14.5 | Dupilumab (5.3) | TCS ± systemic corticosteroids during exacerbations | U | Public | Good |
| Freitas (2024) | Retrospective multi‐centre | N/A | Portugal | Fulfilled the diagnostic guideline | 24 | 42 | 35.6 ± 13.7 | 27 (64.3) | 26.8 ± 8.5 | Dupilumab (40.5), omalizumab (4.8) | N/A | B | None | Fair |
| Gargiulo (2024) | Retrospective multi‐centre | From Jun 2023 to Jun 2024 | Italy | Fulfilled the guideline criteria for abrocitinib treatment by the EuroGuiDerm and failure to cyclosporine | 16 | 85 | 37.8 ± 15.1 | 53 (62.4) | 23.5 ± 9.4 | Dupilumab (47.1) | Topical treatment | A | Private | Good |
| Gregoriou (2025) | Retrospective single centre | From Apr 2022 to Sep 2024 | Greece | Moderate to severe disease severity with a significant impact on the QoL | 96 | 36 | 34.0 ± 16.9 | 20 (55.6) | 30.0 ± 15.2 | Dupilumab (27.8) | Topical treatment | U | None | Good |
| Hagino (2023) | Retrospective single centre | From Aug 2021 to Sep 2022 | Japan | Fulfilled the Japanese AD Guideline 2021 and EASI > 7 | 12 | 36 | 43.8 ± 15.3 | 28 (77.8) | 21.2 (17.3–28.1) | Dupilumab (8.3), Upadacitinib (2.8) | TCS | B | None | Good |
| Hagino (2024) | Retrospective single centre | From Aug 2021 to Sep 2023 | Japan | Fulfilled the Japanese AD Guideline 2021 and EASI ≥ 16 or EASI of head and neck ≥ 2.4 | 48 | U15: 216 | 36 (16–51.5) | 154 (71.3) | 23.9 (17.2–32.0) | Dupilumab (5.6), Baricitinib (1.9) | TCS | U | None | Good |
| U30: 71 | 40 (33–48) | 55 (77.5) | 13.0 (8.6–19.6) | Dupilumab (16.9), Baricitinib (38.0) | ||||||||||
| Hu (2024) | Single centre | N/A | China | Fulfilled the diagnostic guidelines of Hanifin and Rajka and Chinese criteria for AD | Mean: 9.1 | 21 | 46.8 ± 16.1 | 11 (52.4) | 20.8 ± 17.0 | Dupilumab (33.3), Baricitinib (4.8), Upadacitinib (4.8) | N/A | A | Public | Fair |
| Kamphuis (2024) | Retrospective multi‐centre | From Mar 2022 to Jun 2023 | Netherlands | Patients with AD and hand eczema | 28 | 103 | 37.3 ± 14.6 | 61 (59.2) | 17.6 ± 12.7 | Dupilumab (80.6), Upadacitinib (36.9), Baricitinib (15.5), tralokinumab (6.8) | TCS, TCI | A | Private | Good |
| Keow (2024) | Retrospective single centre | N/A | Canada | Failure to dupilumab and/or tralokinumab | 16 | 25 | 31.2 ± 10.8 | 10 (40.0) | 20.4 [16–32] | Dupilumab (80.0), tralokinumab (24.0) | N/A | A | None | Fair |
| Kosaka (2022) | Retrospective multi‐centre | From Jan 2021 to Jun 2022 | Japan | Fulfilled the diagnostic guideline | 12 | 17 | 18.2 ± 38.3 | 13 (76.5) | 25 ± 15 | N/A | TCS | U | None | Good |
| Li (2023) | Prospective single centre | From Jun 2022 to Oct 2023 | China | SCORAD ≥ 25 | 12 | 25 | 32.3 ± 18.6 | 15 (60.0) | 18.0 (12.9–26.0) | Dupilumab (16.0) | TCS, TCI | U | Public | Fair |
| Li (2025) | Prospective single centre | From Sep 2022 to Feb 2024 | China | Fulfilled the diagnostic guidelines of Hanifin and Rajka and Chinese criteria for AD | 12 | 114 | 40.4 ± 17.3 | 73 (62.4) | 15.0 (8.9–21.0) | Dupilumab (23.9) | TCS, TCI | A | Public | Good |
| Lim (2024) | Retrospective single centre | From Jun 2021 to Jun 2 2022 | South Korea | EASI ≥ 16 | 16 | 34 | 35.4 ± 12.6 | 20 (58.8) | 18.7 (N/A) | Dupilumab (35.3) | AH, TCS, TCI | B | None | Fair |
| Liu (2023) | Retrospective single centre | From Jun 2020 to Apr 2022 | China | EASI ≥ 16, IGA ≥ 3 | 16 | 51 | 42.1 ± 13.2 | 28 (54.9) | 33.0 (21.0–42.0) | N/A | N/A | B | Public | Good |
| Melgosa Ramos (2023) | Retrospective multi‐centre | From May 2021 to January 2023 | Spain | Patients with moderate to severe AD, initially based on disease severity | 52 | 21 | 37.8 [10–71] | 10 (48.7) | 19.8 ± 6.5 | Dupilumab (57.4) | No other immunosuppressants | U | Private | Fair |
| Musters (2024) | Prospective multi‐centre | From Oct 2017 to May 2022 | Netherlands and Belgium | Fulfilled the UK Working Party diagnostic criteria | 48 | 23 (B: 10, U: 13) | 33 (22.8–49.3) b | N/A (55.6) b | N/A | N/A | N/A | B, U | Public, private | Fair |
| Na (2023) | Retrospective single centre | Up to June 2022 | Korea | Failure to immunosuppressants and/or dupilumab | 16 | 17 | 36.4 ± 17.2 | 13 (76.5) | 19.0 ± 11.6 | Biologics (e.g., dupilumab; 11.8) | TCS, TCI, AH | U | N/A | Good |
| Naharro‐Rodríguez (2024) | Retrospective single centre | From May 2022 to Apr 2023 | Spain | Failure to corticosteroids and cyclosporine | 24 | 11 | 29 [13–52] | 5 (45.5) | 28.0 (25.5–34.3) | Dupilumab (90.1), Baricitinib (9.1) | N/A | U | N/A | Fair |
| Navarro‐Trivino (2024) | Retrospective multi‐centre | N/A | Spain | Patients with moderate to severe AD | 16 | 13 | 42 [20–61] | 9 (69.2) | 22.5 ± 2.4 | Dupilumab (45.4) | N/A | B | None | Fair |
| Olisova (2024) | Prospective single centre | From 2023 to 2024 | Russia | Patients with moderate to severe AD prone to frequent relapse | 8 | 20 | 40.6 ± 13.7 | N/A | N/A | N/A | NB‐UVB | A | None | Fair |
| Olydam (2023) | Prospective single centre | From Apr 2021 to Dec 2022 | Netherlands | Fulfilled the criteria for abrocitinib treatment by the Dutch Society of Dermatology and Venerology | Median: 28 | 41 | 29 (23.5–40.0) | 21 (51.2) | 14.3 (10.4–24.4) | Dupilumab (75.6), Baricitinib (36.6), Upadacitinib (24.4) tralokinumab (14.6) | TCS, TCI | A | None | Fair |
| Pezzolo (2024) | Retrospective multi‐centre | From Nov 2020 to Aug 2023 | Italy | Failure to conventional treatments | 72 | 325 | 38.6 ± 15.6 | 198 (60.9) | 22.6 ± 11.3 | Biologics (56.9) | TCS, TCI | U | None | Good |
| Rankin (2024) | Retrospective multi‐centre | N/A | Canada | AD with previous therapy | 20–52 | 179 | 44.6 ± 17.5 | 83 (46.4) | 13.4 ± 12.6 | Biologics (37.4) | N/A | U | None | Fair |
| Reguiai (2023) | Prospective multi‐centre | From Dec 2020 | France | Moderate to severe AD | 52 | 88 | 34.5 ± 15.2 | 30 (34.1) | 20.7 ± 12.9 | Dupiluamb (28.4) | TCS, TCI | B | Private | Fair |
| Rogner (2022) | Single centre | From Nov to Jan 2021 | Germany | Moderate to severe AD | 12 | 12 | 33.5 [27–65] | 11 (91.7) | 16.9 (N/A) | Dupiluamb (50.0) | TCS, TCI | B | N/A | Good |
| Sanchez (2025) | Multi‐centre | N/A | Colombia | SCORAD ≥ 20 and failure to immunosuppressants | 52 | 27 | 30.2 ± 9.1 | 14 (51.9) | N/A | N/A | N/A | B | Public | Fair |
| Schlösser (2024) | Prospective single‐centre cohort study | From Aug to Sep 2022 | Netherlands | Failure to previous systemic treatment | Median: 37.5 | 48 | 37 (27–49) | 26 (54.2) | N/A | Dupilumab (72.9), Baricitinib (43.8), Abrocitinib (8.3), tralokinumab (4.2) | TCS, TCI | U | None | Fair |
| Taximaimaiti (2024) | Retrospective single centre | From Jan 203 to Jun 2023 | China | EASI ≥ 16 and failure to topical treatment | 24 | 51 | 36.3 ± 12.2 | 27 (52.9) | 28.4 ± 9.2 | N/A | TCS, TCI | A | N/A | Good |
| Tong (2023) | Prospective single centre | From Jun 2022 to Nov 2022 | China | IGA ≥ 3, EASI ≥ 16, BSA involvement ≥ 10%, NRS ≥ 4, and failure to dupilumab | 12 | 16 | 25 (22–31) | 10 (62.5) | 16.63 ± 4.48 | Dupilumab (100.0) | N/A | A | Public | Good |
| Traidl (2024) | Prospective multi‐centre | From Dec 2017 | Germany | Fulfilled the UK Working Party diagnostic criteria | 12 | 26 | 43.7 ± 15.5 | 20 (76.9) | 21.5 ± 13.2 | Dupilumab (49.0) b | Topical treatment | B | Private | Fair |
| Tran (2023) | Retrospective single centre | From Nov 2021 to Feb 2023 | Australia | Severe chronic AD | Median: 44.7 | 10 | 41.9 ± 13.5 | 6 (60.0) | 27.3 ± 4.9 | Dupilumab (60.0), Baricitinib (30.0) | TCS, TCI | U | N/A | Fair |
| Uchiyama (2022) | Retrospective single centre | From Jul 2020 to Dec 2021 | Japan | Fulfilled the diagnostic guideline | 12 | 14 | 41.0 ± 17.8 | 12 (85.7) | 31.2 ± 14.9 | N/A | TCS | B | Public | Good |
| Uchiyama (2024) | Retrospective single centre | From Sep 2021 to Nov 2023 | Japan | Fulfilled the Japanese AD Guideline 2020 | 12 | 12 | 29.8 ± 19.1 | 8 (66.7) | 31.8 ± 17.2 | N/A | TCS | A | N/A | Good |
| Valente (2025) | Prospective multi‐centre | N/A | Portugal | Failure to 2 conventional systemic immunosuppressants, dupilumab, and baricitinib | 26 | 14 | 29.9 [20.‐51] | 9 (64.3) | 29.3 ± 7.4 | N/A | N/A | U | N/A | Fair |
| Vanlerberghe (2023) | Retrospective multi‐centre | From Mar 2021 to Jan 2022 | France | Failure to conventional systemic treatment and biologics | 26 |
100 (B: 34, U15: 54, U30: 12) |
34 (26–47) | 66 (66.0) | 15.6 (10.5–25.0) | Dupilumab (78.8), others (21.4) | Topical and systemic treatment | B, U | None | Fair |
| Vittrup (2023) | Prospective multi‐centre | From Oct 2017 | Denmark | Failure to conventional systemic treatment | 16 | 44 | 43 (29–44) | 31 (70.5) | 11.1 (6.9–17.4) | Dupilumab (38.6) | TCS | B | Private | Fair |
| Watanabe (2024) | Retrospective single centre | From Jan 2021 to Feb 2023 | Japan | Fulfilled the criteria for baricitinib treatment | 12 | 30 | 31.8 ± 11.4 | 20 (66.7) | 20.2 ± 13.2 | Dupilumab (20.0), Upadacitinib (3.3) | N/A | B | N/A | Good |
| Yang (2024) | Retrospecitve single centre | From May 2022 to Mar 2024 | China | EASI ≥ 16 and failure to conventional treatment | 12 | 46 | 26 (22–31.8) | 17 (37.0) | 21.3 (17.6–25.5) | N/A | TCS, TCI | U | Public | Good |
Abbreviations: A, Abrocitinib; AD, atopic dermatitis; AH, antihistamine; B, Baricitinib; JAK inhibitors, Janus kinase inhibitors; N/A, not available; NOS, Newcastle‐Ottawa Scale; TCI, topical calcineurin inhibitors; TCS, topical corticosteroids; U, Upadacitinib; U15, Upadacitinib 15 mg; U30, Upadacitinib 30 mg.
Age and baseline EASI were reported as mean ± standard deviation, median (interquartile range), or median [range].
Descriptive statistics were only available for the entire population.
The meta‐analysis results of the effectiveness of JAK inhibitors in atopic dermatitis are shown in Table 2, and their forest plots and funnel plots are displayed in Figures S1–S6. The pooled proportions achieving EASI50, EASI75, and EASI90 generally increased over time. EASI50 rates increased from 66.7% (95% CI: 55.6, 77.0) at week 4 to 89.8% (95% CI: 78.3, 97.8) at week 16. Similarly, EASI75 increased from 44.0% (95% CI: 33.6, 54.7) at week 4 to 86.2% (95% CI: 72.2, 96.1) at week 52. The EASI90 showed a consistent increase, rising from 22.4% at week 4 (95% CI: 15.4, 30.1) to 47.2% (95% CI: 28.4, 66.4) at week 24. Substantial heterogeneity was observed, with I 2 values spanning from 74.3 to 88.8, and no publication bias was observed (p > 0.05 for all analyses). In subgroup analyses, EASI50 was comparable across the different types of JAK inhibitor, but EASI75 and EASI90 were often more favourable for upadacitinib. Sensitivity analyses of prospective studies and those rated as good yielded similar trends (Tables S2 and S3), although the number of included studies was limited at certain time points.
TABLE 2.
Proportions of patients achieving EASI50, EASI75, and EASI90 with Janus Kinase (JAK) inhibitors in patients with moderate to severe atopic dermatitis.
| Outcome | Drug | Number of studies (cases/total number of patients) | Pooled proportion (%, 95% CI) | I 2 | p a |
|---|---|---|---|---|---|
| EASI50 | |||||
| Week 4 | Overall | 16 (373/541) | 66.7 (55.6–77.0) | 82.1 | 0.597 |
| Abrocitinib | 4 (169/236) | 59.9 (28.2–87.8) | 91.2 | ||
| Baricitinib | 8 (134/213) | 66.2 (50.3–80.6) | 81.7 | ||
| Upadacitinib | 4 (70/92) | 74.7 (60.2–87.0) | 45.5 | ||
| Week 8 | Overall | 7 (221/262) | 83.1 (70.2–93.1) | 74.3 | 0.163 |
| Abrocitinib | 4 (113/137) | 78.0 (52.2–96.2) | 83.6 | ||
| Baricitinib | 2 (65/79) | 83.0 (71.8–92.0) | 25.8 | ||
| Upadacitinib | 1 (43/46) | 93.5 (84.1–99.2) | — | ||
| Week 12 | Overall | 15 (361/441) | 83.4 (72.5–92.2) | 83.5 | 0.879 |
| Abrocitinib | 4 (124/145) | 86.2 (77.9–93.0) | 23.1 | ||
| Baricitinib | 8 (165/213) | 81.5 (62.3–95.4) | 88.3 | ||
| Upadacitinib | 3 (72/83) | 86.9 (57.2–100.0) | 88.4 | ||
| Week 16 | Overall | 7 (177/201) | 89.8 (78.3–97.8) | 78.4 | 0.736 |
| Abrocitinib | 2 (65/77) | 85.5 (75.1–93.7) | 11.8 | ||
| Baricitinib | 3 (92/100) | 92.7 (66.9–100.0) | 89.3 | ||
| Upadacitinib | 2 (20/24) | 83.7 (65.0–96.9) | 0.0 | ||
| EASI75 | |||||
| Week 4 | Overall | 26 (513/1094) | 44.0 (33.6–54.7) | 85.8 | 0.049 |
| Abrocitinib | 7 (173/380) | 33.0 (16.3–52.0) | 85.2 | ||
| Baricitinib | 9 (78/241) | 34.0 (24.3–44.4) | 58.9 | ||
| Upadacitinib | 10 (262/473) | 60.5 (41.1–78.4) | 88.3 | ||
| Week 8 | Overall | 9 (153/301) | 44.5 (27.5–62.0) | 86.5 | 0.900 |
| Abrocitinib | 4 (82/137) | 43.8 (7.5–84.2) | 93.5 | ||
| Baricitinib | 3 (41/101) | 42.7 (26.2–60.0) | 66.3 | ||
| Upadacitinib | 2 (30/63) | 47.6 (35.1–60.3) | 0.0 | ||
| Week 12 | Overall | 25 (643/1006) | 58.6 (50.7–66.3) | 80.3 | 0.099 |
| Abrocitinib | 5 (153/221) | 58.9 (39.2–77.4) | 80.4 | ||
| Baricitinib | 10 (132/275) | 49.9 (37.1–62.6) | 73.0 | ||
| Upadacitinib | 10 (358/510) | 67.2 (57.8–76.0) | 65.6 | ||
| Week 16 | Overall | 17 (609/792) | 72.8 (63.5–81.3) | 83.1 | 0.045 |
| Abrocitinib | 5 (150/224) | 66.7 (55.5–77.1) | 65.2 | ||
| Baricitinib | 5 (82/130) | 61.3 (46.3–75.4) | 60.8 | ||
| Upadacitinib | 7 (377/438) | 84.8 (71.3–95.0) | 73.1 | ||
| Week 24 | Overall | 10 (305/436) | 69.7 (56.7–81.4) | 75.6 | 0.435 |
| Abrocitinib | 3 (91/135) | 66.1 (50.8–79.9) | 62.7 | ||
| Baricitinib | 1 (24/42) | 57.1 (41.8–71.8) | — | ||
| Upadacitinib | 6 (190/259) | 74.0 (52.3–91.4) | 80.4 | ||
| Week 52 | Overall | 5 (282/332) | 86.2 (72.2–96.1) | 83.1 | < 0.001 |
| Baricitinib | 1 (29/47) | 61.7 (47.3–75.2) | — | ||
| Upadacitinib | 4 (253/285) | 89.8 (85.8–93.2) | 50.9 | ||
| EASI90 | |||||
| Week 4 | Overall | 21 (227/996) | 22.4 (15.4–30.1) | 78.3 | 0.001 |
| Abrocitinib | 5 (90/348) | 25.5 (20.9–30.3) | 0.0 | ||
| Baricitinib | 7 (20/186) | 9.8 (4.3–16.8) | 43.8 | ||
| Upadacitinib | 9 (117/462) | 31.5 (17.5–47.3) | 85.9 | ||
| Week 8 | Overall | 7 (75/269) | 24.2 (14.1–35.9) | 78.3 | < 0.001 |
| Abrocitinib | 2 (47/105) | 44.6 (34.9–54.5) | 0.0 | ||
| Baricitinib | 3 (14/101) | 13.5 (7.0–21.4) | 2.4 | ||
| Upadacitinib | 2 (14/63) | 22.0 (12.2–33.4) | 0.0 | ||
| Week 12 | Overall | 17 (350/851) | 35.9 (26.5–45.7) | 86.9 | 0.099 |
| Abrocitinib | 3 (99/189) | 45.5 (23.5–68.4) | 76.5 | ||
| Baricitinib | 7 (50/202) | 24.9 (16.8–33.9) | 40.1 | ||
| Upadacitinib | 7 (201/460) | 41.4 (24.3–59.5) | 91.2 | ||
| Week 16 | Overall | 16 (384/767) | 44.2 (31.4–57.3) | 88.8 | 0.023 |
| Abrocitinib | 4 (74/199) | 33.9 (20.3–48.8) | 77.5 | ||
| Baricitinib | 5 (37/130) | 28.3 (19.1–38.4) | 24.7 | ||
| Upadacitinib | 7 (273/438) | 62.2 (40.0–82.2) | 86.7 | ||
| Week 24 | Overall | 9 (191/425) | 47.2 (28.4–66.4) | 86.9 | 0.853 |
| Abrocitinib | 3 (64/135) | 44.4 (29.9–59.3) | 63.2 | ||
| Baricitinib | 1 (17/42) | 40.5 (26.0–55.8) | — | ||
| Upadacitinib | 5 (110/248) | 50.9 (16.4–85.0) | 92.7 | ||
p values for subgroup differences.
Figure 2 illustrates the percentage change in the EASI score from baseline over the follow‐up period. Figures S7 and S8 shows the corresponding forest plots and funnel plots. Overall, there was an EASI reduction of 63.3% (95% CI: 57.2, 69.3) at week 4, 69.3% (95% CI: 61.8, 76.8) at week 8, 74.6% (95% CI: 68.7, 80.6) at week 12, 75.8% (95% CI: 68.7, 82.9) at week 16, and 81.7% (95% CI: 73.9, 89.5) at week 24, demonstrating a progressive improvement in symptoms. I 2 values ranged from 70 to 89.7, reflecting substantial heterogeneity, and no evidence of publication bias was detected (p > 0.05 for all analyses).
FIGURE 2.
The percentage change in the Eczema Area and Severity Index (EASI) score from baseline over the follow‐up period.
Pruritus NRS, POEM, ADCT, and DLQI scores were significantly reduced after treatment (Table 3, Figures S9–S16). Pruritus NRS decreased from −4.6 (95% CI: −5.2, −4.0) at week 4 to a maximum reduction of −5.4 (95% CI: −6.5, −4.2) at week 16 and maintained a decrease of −4.9 (95% CI: −5.5, −4.2) at week 24, with I 2 values ranging from 64.3% to 92.6%. POEM scores showed a substantial decline, with a reduction from −8.6 (95% CI: −10.4, −6.9) at week 4 to −9.8 (95% CI: −12.3, −7.2) at week 12, and remained improved at −8.5 (95% CI: −11.1, −5.8) by week 16, with an I 2 range of 61.3% to 83.2%. The ADCT and DLQI scores significantly decreased at all time points.
TABLE 3.
Mean differences in peak NRS, POEM, ADCT, and DLQI scores before and after treatment with Janus Kinase (JAK) inhibitors in patients with moderate to severe atopic dermatitis.
| Outcome | Number of studies (n = total number of patients) | Pooled mean difference (95% CI) | I 2 |
|---|---|---|---|
| NRS | |||
| Week 4 | 26 (n = 913) | −4.6 (−5.2, −4.0) | 91.3 |
| Week 8 | 7 (n = 259) | −4.7 (−5.2, −4.2) | 64.3 |
| Week 12 | 15 (n = 709) | −4.8 (−5.4, −4.2) | 80.0 |
| Week 16 | 9 (n = 266) | −5.4 (−6.5, −4.2) | 92.5 |
| Week 24 | 9 (n = 463) | −4.9 (−5.5, −4.2) | 77.4 |
| POEM | |||
| Week 4 | 12 (n = 406) | −8.6 (−10.4, −6.9) | 69.8 |
| Week 8 | 5 (n = 215) | −9.3 (−11.4, −7.2) | 61.3 |
| Week 12 | 7 (n = 134) | −9.8 (−12.3, −7.2) | 63.4 |
| Week 16 | 6 (n = 223) | −8.5 (−11.1, −5.8) | 83.2 |
| ADCT | |||
| Week 4 | 6 (n = 403) | −9.6 (−10.9, −8.3) | 60.6 |
| Week 12 | 6 (n = 372) | −11.2 (−12.7, −9.6) | 74.1 |
| DLQI | |||
| Week 4 | 16 (n = 570) | −7.5 (−9.4, −5.6) | 90.7 |
| Week 8 | 7 (n = 272) | −8.7 (−11.2, −6.3) | 92.4 |
| Week 12 | 9 (n = 329) | −10.1 (−12.5, −7.6) | 87.0 |
| Week 16 | 11 (n = 328) | −10.0 (−13.1, −7.0) | 94.2 |
| Week 24 | 7 (n = 284) | −9.2 (−11.5, −6.9) | 85.3 |
Abbreviations: ADCT, Atopic Dermatitis Control Tool; DLQI, Dermatology Life Quality Index; NRS, Numerical Rating Scale, POEM, Patient‐Oriented Eczema Measure.
Table 4 and Figures S17–S28 display the adverse events among patients with atopic dermatitis treated with JAK inhibitors. Acne (15.5%; 95% CI: 12.1, 19.1) was the most frequently reported adverse event, followed by increased levels of creatine phosphokinase (CPK; 13.4%; 95% CI: 6.9, 21.3) and increased levels of lipids (11.8%; 95% CI: 7.4, 16.9). In terms of infections, 6.1% (95% CI: 3.9, 8.6) and 2.0% (95% CI: 1.0, 3.3) of patients had herpes simplex and herpes zoster, respectively, whereas 6.0% (95% CI: 3.3, 9.2) of patients had respiratory infections. For gastrointestinal adverse events, nausea and vomiting occurred in 6.9% (95% CI: 4.1, 10.2) of patients, abdominal pain in 6.0% (95% CI: 2.2, 11.2) and diarrhoea in 1.8% (95% CI: 0.0, 6.6). Regarding laboratory abnormalities, 3.5% (95% CI: 2.3, 4.9) of patients had anaemia and 3.4% (95% CI: 2.2, 4.8) had increased liver enzymes. When comparing the types of JAK inhibitors, most adverse events had a similar prevalence, with a few exceptions. In most studies, no serious adverse events were reported, except for one case each of cutaneous lymphoma associated with abrocitinib [26] and anal cancer associated with upadacitinib [58]. Two cases of venous thromboembolism with upadacitinib were reported in two studies [58, 60].
TABLE 4.
Safety of Janus Kinase (JAK) inhibitors in patients with moderate to severe atopic dermatitis.
| Outcome | Drugs | Number of studies (cases/total number of patients) | Pooled proportion (%, 95% CI) | I 2 | p a |
|---|---|---|---|---|---|
| Infection | |||||
| Eczema Herpeticum | Overall | 5 (8/384) | 1.9 (0.0–5.2) | 10.5 | 0.641 |
| Baricitinib | 3 (3/83) | 3.5 (0.2–9.3) | 0.0 | ||
| Upadacitinib | 2 (5/301) | 1.7 (0.0–10.2) | 51.0 | ||
| Herpes simplex | Overall | 22 (86/1451) | 6.1 (3.9–8.6) | 59.5 | 0.633 |
| Abrocitinib | 5 (18/302) | 4.7 (1.0–10.3) | 65.9 | ||
| Baricitinib | 5 (12/172) | 6.5 (3.0–11.2) | 0.0 | ||
| Upadacitinib | 12 (56/977) | 7.4 (3.6–12.1) | 70.6 | ||
| Herpes zoster | Overall | 12 (34/994) | 2.0 (1.0–3.3) | 0.0 | 0.317 |
| Abrocitinib | 2 (3/179) | 1.7 (0.1–4.3) | 0.0 | ||
| Baricitinib | 2 (2/45) | 4.1 (0.0–13.0) | 0.0 | ||
| Upadacitinib | 8 (29/770) | 2.1 (1.0–3.6) | 0.0 | ||
| Respiratory infection | Overall | 21 (63/1376) | 6.0 (3.3–9.2) | 72.0 | 0.495 |
| Abrocitinib | 4 (17/245) | 6.3 (3.3–10) | 0.0 | ||
| Baricitinib | 6 (18/191) | 8.9 (4.1–15.0) | 35.8 | ||
| Upadacitinib | 11 (28/940) | 4.7 (1.2–9.7) | 74.3 | ||
| Soft tissue infection | Overall | 10 (12/721) | 1.5 (0.2–3.5) | 40.8 | 0.044 |
| Abrocitinib | 2 (2/154) | 1.2 (0.0–3.9) | 0.0 | ||
| Baricitinib | 3 (5/76) | 6.3 (1.3–13.5) | 0.0 | ||
| Upadacitinib | 5 (5/491) | 0.7 (0.0–2.7) | 32.9 | ||
| Urinary tract infection | Overall | 6 (12/717) | 1.6 (0.3–3.6) | 50.8 | 0.016 |
| Abrocitinib | 3 (3/305) | 1.0 (0.1–2.6) | 0.0 | ||
| Baricitinib | 1 (5/51) | 9.8 (2.9–19.7) | — | ||
| Upadacitinib | 2 (4/361) | 0.8 (0.0–3.0) | 18.0 | ||
| Skin‐related | |||||
| Acne | Overall | 34 (285/1834) | 15.5 (12.1–19.1) | 70.0 | 0.079 |
| Abrocitinib | 10 (82/522) | 15.6 (9.3–23.1) | 75.0 | ||
| Baricitinib | 9 (23/243) | 9.1 (3.8–15.9) | 53.0 | ||
| Upadacitinib | 15 (180/1069) | 18.7 (14.2–23.7) | 70.7 | ||
| Folliculitis | Overall | 6 (13/307) | 3.2 (1.2–5.9) | 9.0 | 0.593 |
| Abrocitinib | 2 (7/119) | 8.2 (0.0–28.0) | 74.2 | ||
| Baricitinib | 1 (1/22) | 4.6 (0.0–18.5) | — | ||
| Upadacitinib | 3 (5/166) | 2.4 (0.3–5.8) | 0.0 | ||
| Dermatomycosis | Overall | 5 (7/468) | 0.9 (0.0–3.3) | 36.1 | 0.935 |
| Baricitinib | 1 (1/51) | 2.0 (0.0–8.2) | — | ||
| Upadacitinib | 4 (6/417) | 1.1 (0.0–4.7) | 49.1 | ||
| Gastrointestinal | |||||
| Abdominal pain | Overall | 5 (16/246) | 6.0 (2.2–11.2) | 41.1 | 0.108 |
| Abrocitinib | 3 (12/140) | 8.3 (2.9–15.6) | 15.7 | ||
| Baricitinib | 1 (3/42) | 7.1 (0.9–17.3) | — | ||
| Upadacitinib | 1 (1/64) | 1.6 (0.0–6.6) | — | ||
| Diarrhoea | Overall | 6 (7/303) | 1.8 (0.3–3.9) | 0.0 | 0.856 |
| Abrocitinib | 2 (3/115) | 2.2 (0.0–10.8) | 36.0 | ||
| Baricitinib | 3 (3/124) | 2.4 (0.1–6.3) | 0.0 | ||
| Upadacitinib | 1 (1/64) | 1.6 (0.0–6.6) | — | ||
| Nausea/vomiting | Overall | 22 (85/1166) | 6.9 (4.1–10.2) | 76.9 | 0.301 |
| Abrocitinib | 10 (54/456) | 9.4 (4.3–15.6) | 75.2 | ||
| Baricitinib | 5 (12/162) | 7.0 (3.2–11.8) | 0.0 | ||
| Upadacitinib | 7 (19/548) | 4.5 (1.2–9.2) | 74.9 | ||
| General | |||||
| Fatigue | Overall | 12 (30/1051) | 3.2 (1.2–5.7) | 60.0 | 0.471 |
| Abrocitinib | 4 (12/245) | 4.5 (2.0–7.8) | 0.0 | ||
| Baricitinib | 2 (5/76) | 6.4 (1.6–13.5) | 0.0 | ||
| Upadacitinib | 6 (13/730) | 2.1 (0.0–6.2) | 63.0 | ||
| Headache | Overall | 27 (68/1403) | 4.5 (2.7–6.6) | 52.5 | 0.994 |
| Abrocitinib | 8 (30/506) | 4.9 (1.6–9.5) | 70.9 | ||
| Baricitinib | 7 (11/206) | 4.1 (1.4–7.7) | 21.1 | ||
| Upadacitinib | 12 (27/691) | 4.1 (1.7–7.3) | 47.1 | ||
| Weight gain | Overall | 7 (16/407) | 3.4 (1.7–5.7) | 0.0 | 0.405 |
| Abrocitinib | 3 (9/169) | 5.0 (1.9–9.1) | 0.0 | ||
| Baricitinib | 1 (1/25) | 4.0 (0.0–16.4) | — | ||
| Upadacitinib | 3 (6/213) | 2.5 (0.6–5.3) | 5.0 | ||
| Laboratory abnormalities | |||||
| Anaemia | Overall | 14 (41/987) | 3.5 (2.3–4.9) | 0.0 | 0.354 |
| Abrocitinib | 4 (14/280) | 4.4 (1.8–8.0) | 20.8 | ||
| Baricitinib | 1 (4/51) | 7.8 (1.8–17.1) | — | ||
| Upadacitinib | 9 (23/656) | 2.8 (1.5–4.4) | 0.0 | ||
| Increased AST/ALT | Overall | 20 (59/1517) | 3.4 (2.2–4.8) | 8.8 | 0.251 |
| Abrocitinib | 5 (11/397) | 2.6 (1.1–4.6) | 0.0 | ||
| Baricitinib | 4 (6/125) | 4.6 (1.2–9.4) | 0.0 | ||
| Upadacitinib | 11 (42/995) | 4.2 (2.1–6.7) | 40.9 | ||
| Increased creatine phosphokinase | Overall | 20 (164/1465) | 13.4 (6.9–21.3) | 89.1 | 0.046 |
| Abrocitinib | 5 (22/349) | 5.3 (1.1–11.6) | 74.2 | ||
| Baricitinib | 6 (27/173) | 15.1 (9.3–21.8) | 8.1 | ||
| Upadacitinib | 9 (115/943) | 17.9 (3.7–38.5) | 94.3 | ||
| Increased creatinine | Overall | 5 (9/341) | 2.2 (0.7–4.4) | 0.0 | 0.526 |
| Abrocitinib | 1 (1/41) | 2.4 (0–10.2) | — | ||
| Baricitinib | 1 (2/36) | 5.6 (0.1–16.0) | — | ||
| Upadacitinib | 3 (6/264) | 1.9 (0.4–4.1) | 0.0 | ||
| Increased lipids | Overall | 20 (142/1223) | 11.8 (7.4–16.9) | 75.5 | 0.046 |
| Abrocitinib | 4 (23/356) | 5.8 (1.9–11.4) | 72.4 | ||
| Baricitinib | 4 (17/129) | 12.8 (1.4–31.1) | 83.9 | ||
| Upadacitinib | 12 (102/738) | 14.6 (9.1–21.1) | 66.7 | ||
| Lymphopenia | Overall | 7 (13/550) | 3.0 (0.4–7.2) | 69.7 | 0.615 |
| Abrocitinib | 2 (4/136) | 2.8 (0–9.1) | 54.8 | ||
| Baricitinib | 1 (1/12) | 8.3 (0.0–32.4) | — | ||
| Upadacitinib | 4 (8/402) | 3.3 (0.0–10.5) | 79.1 | ||
| Others | |||||
| Arthralgia/myalgia | Overall | 6 (12/618) | 1.9 (0.1–4.9) | 65.3 | 0.616 |
| Abrocitinib | 1 (5/103) | 4.9 (1.4–10) | — | ||
| Baricitinib | 2 (2/76) | 2.4 (0.0–7.8) | 0.0 | ||
| Upadacitinib | 3 (5/439) | 1.1 (0.0–6.3) | 72.6 | ||
| Hair loss | Overall | 5 (7/264) | 2.3 (0.5–4.9) | 0.0 | 0.355 |
| Abrocitinib | 2 (2/144) | 1.2 (0–4.0) | 0.0 | ||
| Baricitinib | 1 (1/25) | 4.0 (0.0–16.4) | — | ||
| Upadacitinib | 2 (4/95) | 4.0 (0.7–9.3) | 0.0 | ||
p values for subgroup differences.
4. Discussion
This meta‐analysis of 50 studies demonstrated a favourable response to systemic JAK inhibitors among patients with moderate to severe atopic dermatitis, showing a gradual increase in all three indices—EASI50, EASI75, and EASI90—over time, along with a manageable safety profile. None of the included studies were classified as poor quality, which enhanced the reliability of this meta‐analysis. Additionally, sensitivity analyses restricted to prospective studies or those rated as good, which helped to mitigate potential bias, yielded similar trends. These results support the robustness of the findings and suggest that study design and quality did not influence the outcomes.
In a JADE EXTEND trial, a long‐term extension study of previous abrocitinib RCTs with topical therapies allowed, EASI75 for abrocitinib 100 and 200 mg were 56.4% and 72.3% at week 12 and 66.8% and 81.7% at week 48 [76]. In a BREEZE‐AD7, baricitinib combined with topical corticosteroids had EASI75 rates of 43%–48% at week 16 [77]. Regarding upadacitinib, the Measure‐up trials reported EASI75 responses for upadacitinib ranging between 60% and 80% at week 16 and 79%–85% for upadacitinib at week 52 [78, 79]. Our meta‐analysis demonstrated that the EASI rates were comparable to the results from RCTs. Given the aim and design of our meta‐analysis, which focuses on RWD, differences in study settings, patient populations, and clinical outcomes between the included observational studies and previous RCTs may limit the direct comparability and warrant caution in interpretation.
When comparing different types of JAK inhibitor, our meta‐analysis found that upadacitinib had the favourable EASI75 and EASI90 response across most time periods, especially after 16 weeks, which aligns with previous findings. A network meta‐analysis of RCTs including patients with atopic dermatitis treated with JAK inhibitors indicated that 30 mg upadacitinib had the highest probability of being the most effective treatment, with a surface under the cumulative ranking value of 0.98 [80], supporting our findings. However, as these results were derived from single‐cohort studies rather than direct head‐to‐head comparisons, they may be influenced by between‐study heterogeneity, including variations in the study setting, patient populations, prior treatments, concomitant therapies, and study designs. Further head‐to‐head trials are warranted to confirm these findings.
According to treat‐to‐target goals, a reduction of at least three points in pruritus NRS, four points in DLQI, and four points in POEM is considered an initial acceptable target, to be reached by 3 months at the latest [81]. Regarding ADCT, a change of five points is regarded as a clinically relevant improvement [82]. In our meta‐analysis, all indexes were achieved early and maintained throughout the entire follow‐up period. This early response aligns with the well‐known rapid antipruritic effects of JAK inhibitors [83].
The most frequently reported adverse events in our meta‐analysis using RWD were acne (16%), increased CPK (13%), and increased lipids (12%). Similar adverse events have been reported in RCTs [84, 85, 86]. However, certain adverse events commonly reported in RCTs, such as nasopharyngitis and headache, were less reported in our RWD, and serious adverse events, such as serious infections, mortality, malignancy, major adverse cardiovascular events, were rarely observed. This may be attributable to the limited length of the follow‐up period and potential under reporting in real‐world settings, which should be considered in clinical decision‐making. Regarding laboratory abnormalities, careful monitoring of laboratory parameters in patients using JAK inhibitors should be considered. According to the practical guide from the International Eczema Council [87], regular laboratory monitoring, including complete blood count, liver enzymes, and lipid profiles, is recommended. CPK levels should be measured if clinical symptoms such as muscle weakness and myalgia are present.
This study has several limitations. First, significant heterogeneity was observed in some analyses. Despite conducting subgroup analyses by types of JAK inhibitor and sensitivity analysis, we could not identify further clinical heterogeneity, which may be due to age, sex, race, and region. Additionally, variability in disease severity (e.g., baseline EASI), prior interventions (e.g., whether patients were biologic‐naïve), and concomitant therapies (e.g., whether topical or systemic agents were allowed) may have contributed to the heterogeneity and influenced the results, which is inherent to the nature of real‐world studies. However, these confounders could not be adjusted for because of the lack of patient‐level information from individual studies. Second, there have been a limited number of studies directly comparing JAK inhibitors with other drugs, leading to many studies adopting a single‐arm cohort design. The absence of comparator groups limits the ability to assess the comparative effectiveness against standard treatments and constrains the application of the GRADE approach to evaluate the overall certainty of evidence. Therefore, the results should be interpreted with caution, considering these methodological limitations. Third, only five of the included studies assessed effectiveness at 52 weeks and we could not extend the analysis beyond that time frame due to a lack of studies. The small number of studies at later time points contributed to imprecision and may have introduced attrition bias, which should be interpreted with caution. Fourth, regarding adverse events, we reported the proportions rather than the incidence rates, because most of the included studies did not provide person‐time data. The pooling of adverse event proportions across studies with different follow‐up durations may introduce bias, because studies with longer follow‐up periods have an increased likelihood of capturing late‐onset events. This should be acknowledged when interpreting the findings of this study. Lastly, although we performed Begg's tests for publication bias, some analyses may be underpowered, particularly those involving fewer than 10 studies, and should therefore be interpreted with caution.
Nevertheless, our study provides quantitative evidence for the effectiveness and safety of systemic JAK inhibitors as a treatment of atopic dermatitis using RWD. This real‐world approach, covering the first year of treatment, allowed the inclusion of a broader and more heterogeneous patient population than typical RCTs, thereby enhancing the generalisability of previous findings by reflecting a diverse range of patients with various demographics, comorbidities, and concomitant therapies. This real‐world evidence may reassure clinicians by complementing the effectiveness and safety previously demonstrated in RCTs. Further head‐to‐head observational studies comparing JAK inhibitors with existing standards, such as biologics, are needed to address the gap in comparative data.
5. Conclusion
Our study describes the overall effectiveness and safety of systemic JAK inhibitors as a treatment of moderate to severe atopic dermatitis in real‐world settings. Our findings confirm that JAK inhibitors are a suitable option for safe and effective treatment of atopic dermatitis, comparable to previous results from RCTs. These findings from real‐world settings provide additional support for the use of JAK inhibitors as a promising treatment option in clinical practice, alongside existing therapies such as immunosuppressants and biologics.
Author Contributions
Y.K. contributed to methodology, software, formal analysis, data curation, investigation, and visualization. G.S. contributed to formal analysis, data curation, investigation, and visualization. J.J.E.K. contributed to conceptualization and investigation. J.Y. contributed to conceptualiztaion, methodology, data curation, investigation, and supervision. All authors contributed to drafting and critically reviewing the manuscript. All authors read and approved the final version of the manuscript.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Data S1: cea70125‐sup‐0001‐Supinfo.pdf.
Acknowledgements
The authors have nothing to report.
Funding: The authors received no specific funding for this work.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1: cea70125‐sup‐0001‐Supinfo.pdf.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.