Research Summary

Long-Term Safety of Baricitinib in Severe Alopecia Areata

Miranda Manier, BA

Key Highlights

  • Up to 4 years of baricitinib exposure in BRAVE-AA1/AA2 revealed no new safety signals.
  • Serious adverse events and discontinuations were infrequent.
  • No new serious/opportunistic infections, MACE, deep vein thromboses, or pulmonary embolisms were observed in the additional year of follow-up.
  • Rates of nonmelanoma skin cancer and other malignancies remained low and stable; no deaths occurred.

A pooled safety analysis from the phase II/III BRAVE-AA1 and phase III BRAVE-AA2 trials found that long-term baricitinib treatment for severe alopecia areata demonstrated a stable and favorable safety profile through a maximum of 4 years of exposure. Most treatment-emergent adverse events (TEAEs) were mild to moderate, and incidence rates of serious events and discontinuations remained low and consistent with earlier reports through 104 weeks or more.

Alopecia areata is a chronic autoimmune disease, and baricitinib—a Janus kinase inhibitor approved in several countries for severe disease—may be used for extended periods. Given the need for durable therapy in an otherwise generally healthy population, characterization of long-term safety is essential to inform ongoing management.

Safety was summarized across two prespecified datasets: an “extended” cohort of patients continuously treated with baricitinib 2 mg or 4 mg, and an “all-baricitinib” cohort that included all patients who received any baricitinib dose at any time during the trials. Incidence rates per 100 patient-years were calculated using time at risk. Data were pooled to the cutoffs of May 22, 2023 (BRAVE-AA1) and May 8, 2023 (BRAVE-AA2), with follow-up through at least 152 weeks and up to 4 years.

In total, 1303 patients contributed 2789.7 patient-years of exposure (median, 825 days; maximum, 1460 days). TEAEs were predominantly mild or moderate. Serious adverse events were uncommon (IR = 2.6), as were discontinuations due to adverse events (IR = 1.7), and both rates were similar to earlier program data. Over the additional year of observation beyond week 104, there were no new cases of serious infections, opportunistic infections, major adverse cardiovascular events, deep vein thrombosis, or pulmonary embolism. The IRs for nonmelanoma skin cancer (IR = 0.1) and other malignancies (IR = 0.2) remained stable. Herpes zoster occurred at a rate consistent with prior reports (IR = 1.9). Laboratory changes were generally consistent over time, and no deaths occurred in either trial.

A limitation of this analysis is that patient numbers in the extended dataset declined after week 52 because of treatment allocation changes, restricting interpretation beyond that time. In addition, the trials excluded patients with uncontrolled comorbidities, recent cardiovascular events, or those at high risk for venous thromboembolism, limiting generalizability. Because adverse events of special interest such as major adverse cardiovascular events, venous thromboembolism, and malignancy are rare, longer observation is required to fully characterize these risks.

“Long-term safety data from BRAVE-AA1 and BRAVE-AA2 are consistent with previously reported data from the baricitinib alopecia areata clinical trial program and demonstrate no new safety concerns or signals for baricitinib through a maximum exposure of 4 years,” Brett King, MD, PhD, and colleagues concluded.

Reference:
King B, Mostaghimi A, Shimomura Y, et al. Safety of baricitinib in adults with severe alopecia areata from two phase III trials over a median of 2.3 years and up to 4 years of teatment. Am J Clin Dermatol. 2025;26(4):611-622. doi:10.1007/s40257-025-00932-0