Kate Johnson

Janus kinase (JAK) inhibitors effectively stimulate hair growth, compared with placebo, for patients with alopecia areata, according to a new systematic review and meta-analysis. Oral JAK inhibitors are more effective than topical formulations.

In an analysis of seven trials that included almost 2000 patients, the odds of achieving 50% improvement were more than five times greater for patients who received JAK inhibitors, compared with patients who received placebo.

"Although the safety and tolerability of JAK inhibitors were acceptable, longer randomized controlled trials are needed to further assess the effectiveness and safety of these treatments for alopecia areata," write study author Ming Liu, PhD, of McMaster University in Hamilton, Ontario, Canada, and colleagues.

The findings were published June 27 in JAMA Network Open.

Indications of Efficacy

Although researchers have investigated the outcomes of JAK inhibitors for alopecia areata, questions remain as to whether the drugs are superior to placebo and whether the route of administration affects outcomes. Investigators conducted a systematic review and meta-analysis to answer these questions.

The analysis encompassed seven randomized controlled trials that included 1710 patients (mean age range, 36.3 – 69.7 years) with alopecia areata. The patients' mean baseline Severity of Alopecia Tool (SALT) scores ranged from 59.5 to 87.9. All trials investigated the efficacy and safety of JAK inhibitors compared with those of placebo. Two studies examined the topical agents ruxolitinib and delgocitinib, and five studies focused on the oral agents ritlecitinib, brepocitinib, deuruxolitinib (CTP-543), and baricitinib.

The primary outcomes of interest were the proportion of patients achieving 30%, 50%, and 90% improvement in SALT score from baseline; change in SALT score from baseline; and treatment-related adverse events.

Five trials that together included 1455 patients reported on change in SALT scores from baseline. Compared with placebo, JAK inhibitors were associated with a greater decrease in SALT scores (mean difference, –34.52) and were not associated with more treatment-related adverse events (relative risk [RR], 1.25).

Compared with placebo, JAK inhibitors were associated with a greater likelihood of SALT 30. But the certainty of evidence regarding SALT 30 results was "very low."

SALT 50 was reported by five trials that together included 482 patients. JAK inhibitors were associated with a greater likelihood of this outcome than placebo (odds ratio [OR], 5.28). SALT 90 was reported by five trials that included 1502 patients. JAK inhibitors were associated with a greater likelihood of achieving this outcome than placebo (OR, 8.15).

They researchers acknowledge that, because of insufficient data, they could not assess the effectiveness and safety of specific oral JAK inhibitors and could not focus on the outcomes of different doses or durations of treatment. "Simply, JAK inhibitors seemed to have resulted in more hair regrowth [compared with placebo], and oral rather than external was a better route of administration," they conclude.

First-Line Option

Commenting on the analysis for Medscape Medical News, Jeff Donovan, MD, a dermatologist at the Donovan Hair Clinic in Whistler, British Columbia, Canada, said that the findings support other systematic reviews and meta-analyses on this topic, which similarly suggest that "all the currently studied JAK inhibitors seem to be somewhat similar in their effectiveness, although this may change as more data accumulate and newer JAK inhibitors are studied."

In a recent review of the topic, Donovan emphasized that JAK inhibitors are now a first-line treatment option for patients with advanced alopecia areata. The US Food and Drug Administration's (FDA's) approvals of baricitinib in 2022 and ritlecitinib in 2023 were important milestones, he added.

While oral JAK inhibitors are superior to topical JAK inhibitors, said Donovan, topical JAK inhibitors may have a role in the management of some aspects of alopecia areata, such as alopecia areata that affects the eyebrows and eyelashes, as well as pediatric alopecia areata. "Oral JAK inhibitors do not help all patients, and, in fact, a very large proportion of patients with advanced alopecia areata do not respond to these drugs as well as we would like," he said. "There is a need for continued research, and the FDA approvals are not an indication that we have reached the finish line, in terms of finding consistently effective treatments for our patients."

He noted that meta-analyses such as the current one "are really important in the alopecia areata field to help clinicians sort through the many different studies. The design of research studies in alopecia areata is quite complex and only getting more complex as time goes on. Meta-analyses give us summaries that we can all relate to, as well as useful numbers and useful statistics that we can share with patients."

The design and clinical utility of such research are also important, said Donovan. "The patients I see every day do not really care that the drug they are using is better than placebo. What most of my patients really and truly care about is that the drug they are using is safe, affordable, easy to use, and highly effective to help them live the life they want."

Much remains to be understood fully, including the long-term safety and efficacy of JAK inhibitors. "We need to keep in mind that use of JAK inhibitors in alopecia areata comes with the same boxed warnings pertaining to cardiac risk, cancer, infections, blood clots, and other issues as when used for other inflammatory and autoimmune issues," said Donovan. "Appropriate patient assessment and counseling will not only help identify individuals who may benefit most from these medications but also will help exclude those who may be at risk for side effects."