Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses

Front Immunol. 2024 Feb 23:15:1342810. doi: 10.3389/fimmu.2024.1342810. eCollection 2024.

Abstract

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.

Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).

Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).

Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).

Keywords: Janus kinase inhibitors; atopic dermatitis; inflammatory network; meta-analyses; umbrella review.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris*
  • Azetidines*
  • Dermatitis, Atopic* / drug therapy
  • Headache
  • Herpes Zoster*
  • Humans
  • Immunoglobulin A / therapeutic use
  • Janus Kinase Inhibitors* / adverse effects
  • Nasopharyngitis*
  • Pruritus / drug therapy
  • Purines*
  • Pyrazoles*
  • Pyrimidines*
  • Sulfonamides*

Substances

  • baricitinib
  • abrocitinib
  • Janus Kinase Inhibitors
  • Immunoglobulin A
  • Purines
  • Sulfonamides
  • Pyrazoles
  • Pyrimidines
  • Azetidines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (grant no. 82074443), Young Qihuang Scholars of the State Administration of Traditional Chinese Medicine (2022-256); Action Plan of "Thickening the Foundation" of Chengdu University of Traditional Chinese Medicine (2023-42), the Sichuan Province Central Guidance of Local Science and Technology Development Project (grant no. 2021YD0089), and the Sichuan Traditional Chinese Medicine Administration of Science and Technology Research Project (grant no. 2021MS307).