This meta-analysis covering 35 clinical trials with a mean follow-up period of 4.9 months aimed to determine all-cause mortality, major adverse cardiovascular events (MACE), and venous thromboembolism (VTE) in individuals with cutaneous conditions. ) to evaluate the risk. Treated with JAK inhibitors. The findings showed that there was no statistically significant difference between patients receiving JAK inhibitors and patients receiving placebo or active comparator in terms of overall MACE, VTE and all-cause mortality. Even in subgroup analyzes comparing oral and topical JAK inhibitors, no significant differences were observed between patients exposed to JAK inhibitors and those who were not.
The results suggest that short-term use of JAK inhibitors for dermatological purposes may not be associated with an increased risk of all-cause mortality, MACE, or VTE. However, it is important to emphasize the need for long-term trials to comprehensively evaluate the safety profile and potential risks associated with long-term use of JAK inhibitors.
Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin conditions such as atopic dermatitis, alopecia areata, and vitiligo, but there is a warning from the U.S. Food and Drug Administration. (FDA) for oral and topical JAK inhibitors in relation to an increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infection, malignancy, and death. However, this boxed warning came from the results of the Oral Rheumatoid Arthritis (ORAL) Surveillance Study, which only included patients with rheumatoid arthritis, and the same association may not be seen in skin conditions.
To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with cutaneous conditions. Data Sources PubMed and ClinicalTrials.gov were searched from database creation to April 1, 2023.
This review included randomized phase 3 clinical trials with placebo/active comparator group of JAK inhibitors used for dermatology indication with FDA approval or pending approval or approval from the EU or Japan. Studies without a comparison group, case reports, observational studies, and review articles were excluded. Data extraction and synthesis This study was conducted in accordance with the Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Adverse events were calculated using odds ratios (OR) and 95% confidence intervals (CI) using a random effects model and the DerSimonian–Layard method. Studies were reviewed, data extracted and quality assessed by 2 independent authors.
The protocol was prospectively registered in PROSPERO. Main Results and Measures Results There was no significant difference between JAK inhibitors and the placebo/active comparator group in overall MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI). Did not show significant difference. , 0.26-1.04).
Conclusion and Relevance
In this systematic review and meta-analysis, JAK inhibitor use was not associated with an increased risk of all-cause mortality, MACE, and VTE compared with placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for cutaneous indications.”
Jeanne P. Ingrassia, Muhammad Haisam Maqsood, Joel M. Gelfand, et al.