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

Abstract

Importance: Janus kinase (JAK) inhibitors are increasingly used across a range of dermatologic conditions. Adverse events of acne have been noted in some studies in clinical practice, but the scope of this outcome across JAK inhibitors has not been established.

Objective: To systematically analyze all published phase 2 and 3 placebo-controlled randomized clinical trials (RCTs) of JAK inhibitors for the risk of acne as an adverse effect of these medications.

Data sources: Comprehensive search of Ovid MEDLINE and PubMed databases through January 31, 2023.

Study selection: Inclusion criteria were phase 2 and 3 placebo-controlled RCTs of JAK inhibitors published in English with reported adverse events of acne.

Data extraction and synthesis: Two reviewers independently reviewed and extracted information from all included studies.

Main outcomes and measures: The primary outcome of interest was the incidence of acne following JAK inhibitor use. A meta-analysis was conducted using random-effects models.

Results: A total of 25 unique studies (10 839 unique participants; 54% male and 46% female) were included in the final analysis. The pooled odds ratio (OR) was calculated to be 3.83 (95% CI, 2.76-5.32) with increased ORs for abrocitinib (13.47 [95% CI, 3.25-55.91]), baricitinib (4.96 [95% CI, 2.52-9.78]), upadacitinib (4.79 [95% CI, 3.61-6.37]), deucravacitinib (2.64 [95% CI, 1.44-4.86]), and deuruxolitinib (3.30 [95% CI, 1.22-8.93]). Estimated ORs were higher across studies investigating the use of JAK inhibitors for the management of dermatologic compared with nondermatologic conditions (4.67 [95% CI, 3.10-7.05]) as well as for JAK1-specific inhibitors (4.69 [95% CI, 3.56-6.18]), combined JAK1 and JAK2 inhibitors (3.43 [95% CI, 2.14-5.49]), and tyrosine kinase 2 inhibitors (2.64 [95% CI, 1.44-4.86]).

Conclusions and relevance: In this systematic review and meta-analysis, JAK inhibitor use was associated with an elevated odds of acne. Patients should be properly counseled on this potential adverse effect of these medications before treatment initiation. Future studies are needed to further elucidate the pathophysiology of this association.

Figure 1.. Study Flow Diagram

Figure 2.. Summary of Janus Kinase Inhibitors and Associations With Acne

Arrows indicate upper bound of 95% CI greater than 15.00; size of markers, number of participants in each group; and width of diamond, upper and lower bound of 95% CI for pooled estimate of the odds ratio (OR).

Figure 3.. Subgroup Analysis by Janus Kinase (JAK) Inhibitor Specificity

Arrows indicate upper bound of 95% CI greater than 8.00; size of markers, number of participants in each group; and width of diamond, upper and lower bound of 95% CI for pooled estimate of the odds ratio (OR). TYK2 indicates tyrosine kinase 2.

Figure 4.. Subgroup Analyses by Indication

Arrows indicate upper bound of 95% CI greater than 15.00; size of markers, number of participants in each group; and width of diamond, upper and lower bound of 95% CI for pooled estimate of the odds ratio (OR).