Baricitinib: A potential treatment for alopecia areata?
Baricitinib, an oral, selective Janus kinase (JAK)1/JAK2 inhibitor, may help improve hair growth in patients with severe alopecia areata, according to results from the phase III BRAVE-AA1 and BRAVE-AA2 trials.
The study population comprised patients aged ≥18 years* who had severe alopecia areata (Severity of Alopecia Tool [SALT] score ≥50) for >6 months to <8 years. A total of 654 and 546 patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, were enrolled. They were randomized 3:2:2 to receive once-daily doses of baricitinib at either 2 or 4 mg or placebo. Mean SALT score at baseline was 85.5 and 85.1 in the BRAVE-AA1 and BRAVE-AA2 trials, respectively.
At week 36, achievement of SALT score ≤20 or ≤20 percent scalp hair loss was greater in patients who received baricitinib 4 mg or 2 mg vs placebo in BRAVE-AA1 (35.2 percent and 21.7 percent vs 5.3 percent; p≤0.001 for both vs placebo) and BRAVE-AA2 (32.5 percent and 17.3 percent vs 2.6 percent; p≤0.001 for both vs placebo). [EADV 2021, abstract N°: 605]
At week 36, the proportion of patients achieving Clinician-Reported Outcomes (CROs) for Eyebrow Hair Loss™ score 0 or 1 (full coverage or minimal gaps) with ≥2-point improvement from baseline** was significantly greater with baricitinib 4 and 2 mg vs placebo in BRAVE-AA1 (31.4 percent and 19.1 percent vs 3.2 percent; p≤0.001 for both vs placebo), but only with baricitinib 4 mg in BRAVE-AA2 (34.8 percent vs 4.5 percent; p≤0.001), with 11.5 percent of patients on baricitinib 2 mg achieving this outcome.
A significantly greater proportion of patients on baricitinib 4 mg than placebo achieved CROs for Eyelash Hair Loss™ score of 0 or 1 with ≥2-point improvement from baseline** in both BRAVE-AA1 (33.5 percent vs 3.1 percent; p≤0.001) and BRAVE-AA2 (34.3 percent vs 5.6 percent; p≤0.001). There was no significant difference in this outcome between patients on baricitinib 2 mg and placebo in BRAVE-AA2 (10.1 percent vs 5.6 percent), though the proportion was greater with baricitinib 2 mg vs placebo in BRAVE-AA1 (13.5 percent vs 3.1 percent; p≤0.05).
Treatment-emergent adverse events (TEAEs) occurred in 59.6, 50.8, and 51.3 percent of baricitinib 4 mg, 2 mg, and placebo recipients, respectively, in BRAVE-AA1, and 66.1, 68.4, and 63.0 percent, respectively, in BRAVE-AA2. Most of the TEAEs were mild or moderate in severity. Serious AEs occurred at a comparable rate between groups (2.1, 2.2, and 1.6 percent, respectively, in BRAVE-AA1, and 3.4, 2.6, and 1.9 percent, respectively, in BRAVE-AA2).
The most common AEs in baricitinib recipients were upper respiratory tract infection, nasopharyngitis, headache, urinary tract infection, acne, and elevated creatine phosphokinase levels. Herpes zoster and herpes simplex occurred at a comparable frequency across treatment groups. Three serious infections occurred in baricitinib-treated patients in BRAVE-AA2.
No deaths, venous thromboembolic events, opportunistic infections, or gastrointestinal perforations occurred in either trial. One baricitinib 2 mg recipient with multiple risk factors in BRAVE-AA1 experienced a major adverse cardiovascular event, while in BRAVE-AA2, one baricitinib 4 mg recipient was diagnosed with B-cell lymphoma and one placebo recipient was diagnosed with prostate cancer.
“No new safety findings were identified compared with the known safety profile of baricitinib established in other indications,” pointed out study author Associate Professor Brett King from the Yale School of Medicine, New Haven, Connecticut, US.
According to King, there are currently no FDA-approved treatments for alopecia areata. “[These] two phase III clinical trials [showed that] … baricitinib 4 mg and 2 mg were superior to placebo in achieving scalp hair regrowth after 36 weeks of treatment [in patients with severe alopecia areata].”
He highlighted that trials are ongoing and longer observation periods will demonstrate the durability of the outcomes, as well as long-term safety of the drug and potential delayed responses.