Baricitinib: Clinical Efficacy and Safety

General Description

Baricitinib has shown promising clinical efficacy in treating Alopecia Areata (AA), with significant improvements in hair regrowth observed in patients receiving the medication, particularly at the 4 mg dose, as demonstrated in the BRAVE-AA1 trial. Patients treated with baricitinib exhibited higher proportions of achieving specific improvements in the Severity of Alopecia Tool (SALT) scores, with a greater percentage reaching SALT scores of ≤ 20 by week 36 compared to the placebo group. The medication was effective in reducing hair loss, as indicated by the percent change from baseline in SALT score and higher response rates in SALT50, SALT75, SALT90, and SALT100 categories. In terms of safety, baricitinib demonstrated a consistent and favorable safety profile across various trials, with manageable adverse events and a low frequency of serious adverse events, supporting its use in treating atopic dermatitis.

Figure 1. Baricitinib

Clinical Efficacy

Baricitinib is a medication that has shown promising clinical efficacy in the treatment of patients with Alopecia Areata, a condition characterized by hair loss. The BRAVE-AA1 trial, a phase 2/3 study, evaluated the effectiveness and safety of oral baricitinib in patients with AA who had at least 50% scalp hair loss. Patients were randomized to receive different doses of baricitinib (1 mg, 2 mg, or 4 mg) or a placebo. The trial included patients with severe or very severe AA, within specific age ranges, and with a current episode of AA lasting a certain duration. Patients with certain types of alopecia or who had recently used specific treatments were excluded from the study. Throughout the trial, no other treatments for AA were allowed. The interim analyses of the trial focused on key endpoints such as the proportion of patients achieving specific improvements in the Severity of Alopecia Tool score at different time points. The results from these analyses guided the selection of doses for further studies. At week 12, a higher percentage of patients treated with baricitinib, particularly the 2 mg and 4 mg doses, showed significant improvements in SALT scores compared to those on placebo. By week 36, a significantly greater proportion of patients in the baricitinib groups achieved a SALT score of ≤ 20 compared to the placebo group. Additionally, patients on baricitinib had a greater percent change from baseline in SALT score, indicating the effectiveness of the medication in reducing hair loss. Furthermore, responses such as SALT50, SALT75, SALT90, and SALT100 were significantly higher in patients treated with baricitinib 4 mg compared to placebo. These findings suggest that baricitinib, especially at the 4 mg dose, is effective in improving hair regrowth and reducing hair loss in patients with AA. Overall, the results of the BRAVE-AA1 trial demonstrate the clinical efficacy of baricitinib in treating AA, with significant improvements in SALT scores and hair regrowth observed in patients receiving the medication. ¹

Safety

Baricitinib has been extensively studied for its safety profile in various clinical trials, including phase II and phase III trials focusing on patients with atopic dermatitis. In these trials, adverse events were carefully monitored to assess the safety and tolerability of baricitinib across different doses. In the phase II trial (NCT02576938), adverse events leading to discontinuation were observed in a small percentage of participants across the placebo and baricitinib groups. The most common adverse events reported in the active arms included abnormal lymphocyte count, neutropenia, headache, and eczema. In the subsequent BREEZE-AD phase III trials, the incidence of adverse events was comparable between the placebo and baricitinib arms. The most common treatment-emergent adverse events included nasopharyngitis, headache, increased serum CPK levels, and upper respiratory tract infections. Across the various trials, serious adverse events were infrequent, with no reports of deaths, cardiovascular events, thrombosis, gastrointestinal perforation, or malignancies associated with baricitinib treatment. While some specific adverse events like herpes simplex infections were observed more frequently in certain dose groups, overall, the safety profile of baricitinib remained consistent and favorable. A pooled safety analysis of baricitinib in adult patients with atopic dermatitis from multiple randomized trials further confirmed the low frequency of serious adverse events, with common treatment-emergent adverse events being nasopharyngitis, headache, CPK elevations, and diarrhea. Importantly, the study did not show an increased risk of serious adverse cardiovascular events or significant skin infections requiring antibiotic treatment with the use of baricitinib. Overall, the safety data from these trials suggest that baricitinib is generally well-tolerated, with manageable adverse events and a safety profile that supports its use in the treatment of atopic dermatitis. ²

Reference

1. Freitas E, Guttman-Yassky E, Torres T. Baricitinib for the Treatment of Alopecia Areata. Drugs. 2023; 83(9): 761-770.

2. Melo A, Carrascosa JM, Torres T. Baricitinib for the treatment of atopic dermatitis. J Dermatolog Treat. 2022; 33(5): 2404-2413.