Breaking Out the Truth: The Acne Risk with JAK Inhibitors

Original Article: Janus Kinase Inhibitors and Adverse Events of Acne: A Systematic Review and Meta-Analysis

What are the key takeaways of this article?

Janus-Kinase signal transducer and activator of transcription (JAK-STAT) signaling plays a pivotal role in the inflammatory pathways of numerous inflammatory conditions. This intricate network is governed by four recognized JAK proteins: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). JAK inhibitors have emerged as valuable treatment options for a wide range of dermatologic, hematologic, and rheumatologic disorders. However, an intriguing phenomenon has surfaced in clinical trials, where acne has been reported as an adverse effect in patients treated with JAK inhibitors. Acne affects patients' self-esteem, mental health, and psychosocial functioning. The primary question of this research revolves around determining whether there is an association between the use of JAK inhibitors and the development of acne.

To address this question, a systematic review and meta-analysis were conducted to investigate the risk of acne associated with the use of JAK inhibitors across all published phase 2 and 3 placebo-controlled randomized clinical trials of these inhibitors. The primary outcome of interest in this analysis was the incidence of acne following the use of JAK inhibitors. The study analyzed data from 25 articles.

The results of this study identified 467 individuals (6.2%) who developed acne after exposure to JAK inhibitors and compared them to 44 cases (1.3%) in the cumulative control group. The calculated pooled odds ratio (OR) was 3.83 (95% CI, 2.76-5.32), indicating a significant increase in the risk of acne. Further analysis revealed that certain JAK inhibitors, including abrocitinib, baricitinib, and upadacitinib displayed increased ORs, reinforcing the association between specific JAK inhibitors and acne incidence.

Subgroup analyses categorized JAK inhibitors into classes, showing that JAK1-specific inhibitors, combined JAK1 and JAK2 inhibitors, and TYK2 inhibitors all presented increased ORs for acne. However, no significant differences were observed in acne incidence for pan-JAK inhibitors or JAK3-specific inhibitors. Another subgroup analysis compared studies focused on the treatment of dermatologic conditions with those addressing other applications, such as ulcerative colitis or rheumatoid arthritis. This analysis highlighted a higher pooled OR for dermatologic studies compared to non-dermatologic ones. No significant associations between sex or age and the effect size of JAK inhibitor use on acne development was identified.

In summary, this comprehensive analysis provides strong evidence for an association between JAK inhibitor use and an increased incidence of acne. The development of acne following treatment with certain classes of JAK inhibitors is a potential concern, as this adverse effect may compromise treatment adherence among some patients. This study highlights the importance of further research to elucidate the underlying mechanisms linking JAK inhibitor use and acne. Such investigations may pave the way for the development of methods to minimize the impact of acne on patients undergoing JAK inhibitor treatment. Furthermore, these findings emphasize the need for healthcare professionals to counsel patients who are prescribed JAK inhibitors about the possibility of developing acne as an adverse outcome. Raising awareness and proactive management of this side effect can help patients make informed decisions and improve their overall treatment experience.

Publication Date: November 27th, 2023

Reference: Martinez J, Manjaly C, Manjaly P, et al. Janus Kinase Inhibitors and Adverse Events of Acne: A Systematic Review and Meta-Analysis. JAMA Dermatol. Published online October 18, 2023. doi:10.1001/jamadermatol.2023.3830

Summary By: Sascha Azoulay