Incremental Risk of Adverse Events with Oral Janus Kinase Inhibitor Use in Atopic Dermatitis and Other Indications: A Systematic Review and Meta-Analysis
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Keywords
Atopic Dermatitis
Abstract
Introduction: The number of treatment opportunities for patients with moderate-severe atopic dermatitis (AD) is increasing, however with varying treatment safety profiles. The safety profile of oral JAKis remains a concern because of their ubiquitous mechanism of action inhibiting many cytokines. Safety warnings for these products have combined data across indications, making it difficult to assess risk for specific populations.
Objective: We aimed to estimate the incremental risk of pre-specified adverse events (AEs) per patient-year (PY) of oral JAKi compared with standard of care (SoC), incl. topical corticosteroids, biologic agents, and other treatments, among those with AD or with other diagnoses.
Methods: A systematic literature review was conducted on 17 preselected AEs based on randomized controlled trials of oral JAKis.
Meta-analyses (MA) estimated the incidence rate difference (IRD) for each AE between oral JAKis and SoC, both in AD and non-AD populations. Number needed to harm (NNH) was calculated as the inverse of the IRD for each AE.
Results: We identified 82 studies, including 19 in AD population, for use in the MA.
In the AD population, the estimated NNH in PY for acne was 5, indicating 1 additional acne event for every 5 patients treated with oral JAKis vs SoC per year. Moreover, the NNH was 33 for herpes zoster, 62 for anemia, 94 for serious adverse events (SAEs), and 452 for malignancies. In the non-AD population, the NNH was 52 for HZ, 56 for hyperlipidemia, 58 for SAEs, 113 for anemia, 153 for acne, and 254 for malignancies.
Conclusions: The MA identified an increased risk with oral JAKis compared with SoC for multiple AEs, spanning from less to more severe AE, including malignancies in both AD and non-AD populations. As safety risks are observed in both the AD and non-AD populations, the use of oral JAKis should be carefully considered.
References
2. Janus Kinase inhibitors (JAKi) Article-20 procedure - Annex - Scientific conclusions (2023). Retrieved 20 July 2023, from https://www.ema.europa.eu/en/documents/referral/janus-kinase-inhibitors-jaki-article-20-procedure-annex-scientific-conclusions_en.pdf.
3. Salas, A., Hernandez-Rocha, C., Duijvestein, M. et al. JAK–STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 17, 323–337 (2020).
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