Jeremy Martinez, MPH

Credit: Harvard University

JAK inhibitor treatment is linked to higher rates of acne among dermatology patients, according to recent findings, suggesting the need for both proper counseling of patients on such adverse effects and further investigation into the underlying mechanisms.¹

These findings were the result of a recent meta-analysis, conducted to assess each of the placebo-controlled phase 2 and phase 3 randomized clinical trials (RCTs) on JAK inhibition treatment that have been published. The analysis looked at acne risk as an adverse effect of the treatments analyzed in each of these studies.

The topic of JAK inhibitor use for different dermatologic conditions has become increasingly prominent among dermatologists, with the pro's and con's being highlighted frequently.

To help add to this body of research, the new analysis into acne rates and JAK inhibition was led by Jeremy Martinez, MPH, from Harvard Medical School in Boston, Massachusetts.

“While JAK inhibitors hold promise as a valuable treatment option for patients with inflammatory conditions, acne has been a commonly reported adverse effect in clinical trials of JAK inhibitors,” Martinez and colleagues wrote. “However, little is known about the overall incidence of acne from JAK inhibitors and how this differs between different drug classes and the underlying conditions being treated.”^2,3

Background and Findings

The investigators used a systematic review and meta-analysis study design, seeking to assess the occurrence of new-onset acne in individuals involved in clinical trials receiving JAK inhibitor treatment compared to those in the placebo arm of the analysis. Their methodological quality was assessed through the Measurement Tool to Assess Systematic Reviews.

In order to gather the relevant RCTs, the research team utilized a comprehensive search strategy with Ovid MEDLINE and PubMed, encompassing placebo-controlled RCTs that involved JAK inhibitor use. The team’s assessment included search terms related to JAK inhibition such as tofacitinib, ruxolitinib, and others, with the assessment being extended from the inception of the databases until January 2023.

The investigators would only consider studies published in English, and they removed duplicates. All research methods, including the research question, search criteria, and risk of bias evaluation, were established before the commencement of the review.

They had 3 reviewers independently look through the RCT titles and abstracts, with the reviewers using their predetermined criteria for inclusion and exclusion. After the first screening, full-text articles were assessed by 2 reviewers, and discrepancies between potential duplicates were resolved through discussion with the principal investigator.

RCTs that included multiple interim reports were looked into, and the investigators only considered the most recent data. Furthermore, for trials transitioning to an open-label phase, only data from blinded phases were utilized.

The research team extracted information on disease indications, types of JAK inhibitors, research subject qualities, and incidence of acne. The team also used subgroup analyses which thet stratified by type of JAK inhibitor and indication (dermatologic vs. nondermatologic), using quantitative synthesis by random-effects meta-analysis whenever it was deemed feasible.

Additionally, the investigators determined statistical significance by a 2-sided P-value of less than 0.05, and the analyses were carried out using R, version 4.

Overall, the research team’s final analysis covered 25 distinct RCTs, with the combined total consisting of 10,839 unique subjects. The team reported that 54% identified as male and 46% female.

The investigators’ pooled odds ratio (OR) was noted as being 3.83 (95% CI, 2.76-5.32). Notably, elevated ORs were reported by the team for specific JAK inhibitors, such as baricitinib (OR 4.96 [95% CI, 2.52-9.78]), abrocitinib (OR 13.47 [95% CI, 3.25-55.91]), deucravacitinib (OR 2.64 [95% CI, 1.44-4.86]), upadacitinib (OR 4.79 [95% CI, 3.61-6.37]), and deuruxolitinib (OR 3.30 [95% CI, 1.22-8.93]).

Additionally, trials looking into JAK inhibitor usage for dermatologic conditions showed higher estimated ORs versus nondermatologic conditions (OR 4.67 [95% CI, 3.10-7.05]). The investigators also noted that JAK1-specific inhibitors (OR 4.69 [95% CI, 3.56-6.18]), combined JAK1 inhibitors and JAK2 inhibitors (OR 3.43 [95% CI, 2.14-5.49]), and tyrosine kinase (TYK)-2 inhibitors (OR 2.64 [95% CI, 1.44-4.86]) showed distinct OR patterns.

The research team concluded that utilization of JAK inhibitors was shown to be linked to an increased likelihood of developing acne, emphasizing the importance of providing patients with comprehensive information about such side effects before commencing treatment.

“Although age and sex differences may exist between trials, our data suggest that differences between drugs are not due to these variations,” they wrote. “Future research is required to determine whether these observed differences are due to clinician evaluation or a function of the underlying physiology of specific diseases.”

References

1. ^{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.}
2. ^{Lee SD, Ahn HJ, Shin MK. A case series of acne following Janus kinase inhibitors in patients with atopic dermatitis. JAAD Case Rep. 2022;30:11-16. doi:10.1016/j.jdcr.2022.09.029.}
3. ^{Klein B, Treudler R, Simon JC. JAK-inhibitors in dermatology–small molecules, big impact? overview of the mechanism of action, previous study results and potential adverse effects. J Dtsch Dermatol Ges. 2022;20(1):19-24. doi:10.1111/ddg.14668.}