JAK inhibitors—especially those administered orally—exhibit greater hair regrowth for alopecia areata (AA) patients versus placebo, according to new findings, indicating a need for longer randomized controlled trials to further examine effectiveness and safety.¹

These findings resulted from a systematic review and meta-analysis of exclusively randomized clinical trials (RCTs) looking into both the efficacy and safety of JAK inhibitors for alopecia.

The research was conducted to expand upon existing knowledge, given that there are several known clinical trials, case reports, and meta-analyses examining JAK inhibitor outcomes with such drugs as ruxolitinib, tofacitinib, and baricitinib, for alopecia.²

To expand this body of literature, the research was authored by Jinhui Tian, PhD, from the Evidence Based Medicine Centre of the School of Basic Medical Sciences at Lanzhou University in China.

“To address the current gaps in knowledge, we performed this systematic review and meta-analysis. We aimed to evaluate the effectiveness and safety associated with JAK inhibitors for AA,” Tian and colleagues wrote.

Background and Findings

The investigators exclusively included in their analysis RCTs that assessed the effectiveness and safety of topical and systemic JAK inhibitors for use by patients with alopecia. No restrictions were placed on patient disease severity, characteristics, duration of treatment, or language of publication.

The team’s search encompassed various databases, reference lists, and citation analyses, including Embase, MEDLINE, and CENTRAL. The data collected by the investigators included patient characteristics, study information, intervention details, and outcomes of interest.

For analysis, multiple records of the same trial were combined by the research team, while separate trials reported within a single record were treated as distinct studies.

Their primary outcomes were the proportion of alopecia patients with specific improvements in Severity of Alopecia Tool (SALT) scores, change in baseline SALT scores, and treatment-related adverse events (AEs).

Secondary outcomes examined by the investigators included the percentage of those reaching certain SALT score thresholds during treatment, the percentage of patients experiencing severe treatment-related AEs, and the percentage of patients discontinuing treatment as a result of AEs.

The research team examined risk of bias in each study through a modified Cochrane tool, considering domains such as blinding, random generation of sequences, incomplete outcome data, and selective reporting of outcomes. The team noted that an outcome showed a higher risk of bias if at least a single domain was rated as being high or probably high risk.

The investigators’ study involved a total of 1710 patients, with 63.3% being females. JAK inhibitors were found to be linked with increased likelihood of achieving 50% (OR, 5.28; 95% CI, 1.69 - 16.46) and 90% (OR, 8.15; 95% CI, 4.42 - 15.03) improvement in SALT scores versus those in the placebo groups, with low certainty.

JAK inhibitors also led to greater reduction in SALT scores from baseline versus placebo (MD, –34.52; 95% CI, −37.80 to −31.24) with moderate certainty. There was no major difference in treatment-related AEs between JAK inhibitors and placebo (RR, 1.25; 95% CI, 1.00 - 1.57) with high certainty.

The investigators added that higher certainty data showed that JAK inhibitors were not linked to more severe adverse events versus placebo. They also stated that their subgroup analysis showed oral JAK inhibitors had been more effective than placebo, while no substantial difference was found between external JAK inhibitors and placebo.

“Although the safety and tolerability of JAK inhibitors were acceptable, longer RCTs are required to further assess their effectiveness and safety,” they wrote. “More trials with larger sample sizes would benefit future meta-analyses or NMAs and may help increase the certainty of evidence. The incomplete reporting of outcomes suggests the need for a core outcome set for AA.”

References

1. ^{Liu M, Gao Y, Yuan Y, et al. Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(6):e2320351. doi:10.1001/jamanetworkopen.2023.20351.}
2. ^{Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33(5):850-856. doi:10.1111/jdv.15489.}