Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials.

BACKGROUND

Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan.

OBJECTIVES

To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods.

METHODS

This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IR) were calculated.

RESULTS

Data were collected for 1303 patients who were given baricitinib, reflecting 1868 patient-years of exposure (median 532 days). The most frequently reported TEAEs during the placebo-controlled period (based on the baricitinib 4-mg group) were upper respiratory tract infection, nasopharyngitis, headache, acne and elevated blood creatine phosphokinase (CPK). During the placebo-controlled period, the frequency of acne was higher with baricitinib than placebo, and elevated CPK was higher with baricitinib 4 mg than placebo and baricitinib 2 mg. In all-BARI, the IR of serious infections was low (n = 16, IR 0.8). There was one opportunistic infection (IR 0.1), and 34 cases of herpes zoster (IR 1.8). There was one positively adjudicated major adverse cardiovascular event (myocardial infarction) (IR 0.1), one pulmonary embolism (IR 0.1), three malignancies other than nonmelanoma skin cancer (IR 0.2) and one gastrointestinal perforation (IR 0.1). No deaths were reported.

CONCLUSIONS

This integrated safety analysis in patients with severe AA is consistent with the overall safety profile of baricitinib. Some differences with atopic dermatitis were noted that may be attributable to the disease characteristics of AA.

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.

Déclaration de conflit d'intérêts

Conflicts of interest: B.K. has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AbbVie, AltruBio Inc, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Myers Squibb, Concert Pharmaceuticals Inc, Equillium, Horizon Therapeutics, Eli Lilly and Company, Incyte Corp, Janssen Pharmaceuticals, LEO Pharma, Otsuka/Visterra Inc, Pfizer Inc, Regeneron, Sanofi Genzyme, TWi Biotechnology Inc and Viela Bio. He is on speaker bureaus for AbbVie, Eli Lilly and Company, Incyte Corp, Pfizer Inc, Regeneron and Sanofi Genzyme. A.M. receives consulting fees from Pfizer, hims and hers, Digital Diagnostics, Concert, Lilly, AbbVie, Bioniz and Acom, holds equity in Lucid, hims, Figure 1, and ACOM, holds licensing/royalties at Pfizer, Concert, Medical Advisory Board at Digital Diagnostics and Figure 1, conducts clinical trials with Incyte, Lilly, Aclaris and Concert and is an Associate Editor at JAMA Dermatology. Y.S. receives advisory fees from Eli Lilly Japan K.K. and Maruho Co. Y.S. also receives research grants for studies not related to this work from Eli Lilly Japan K.K., Maruho Co, and Sun Pharma Japan Ltd. A.Z. is a consultant or is a clinical trial investigator for Eli Lilly and Company and Pfizer. G.-S.C. has served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AmorePacific, Bristol Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, LEO Pharma, Medytox, MSD, Pfizer Inc, Regeneron, Sanofi Genzyme and SCM Lifescience. U.B.-P. served on advisory boards and/or is a consultant and/or is a clinical trial investigator for AbbVie, Amryt, Bayer, Boots Healthcare, Cassiopeia, CeraVe, Concert Pharmaceuticals, Dermocosmétique Vichy, Eli Lilly and Company, Galderma, LEO Pharma, Mayne Pharma Neuroderm, Novartis, Pfizer, Pierre Fabre and Sanofi Regeneron. T.P. reports grants and/or honoraria from AbbVie, ACM Pharma, Almirall, Amgen, Astellas, Bristol Myers Squibb, Celgene, Galderma, Genzyme/Sanofi, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceuticals and UCB; and is the cofounder of YUKIN Therapeutics. K.H., Y.D., J.M., F.E.Y., S.S. and W.-S.W. are employees and shareholders of Eli Lilly and Company. R.S. reported serving as a consultant or paid speaker for or participating in clinical trials sponsored by LEO Pharma, Amgen, Inc, Novartis Pharmaceuticals Corporation, Merck & Co, Celgene Corporation, Coherus BioSciences, Janssen Global Services, LLC, Regeneron Pharmaceuticals Inc, MedImmune, LLC, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingelheim, Pfizer, Inc, Merck Sharpe & Dohme, Oncobiologics, Inc, F. Hoffman–La Roche, Ltd, Eli Lilly and Company, and Bayer AG and is serving as the current President of the Australasian Hair and Wool Research Society.