Continued treatment with baricitinib results in meaningful scalp responses among scalp non‐responder patients with eyebrow/eyelash regrowth in the first year

Alopecia areata (AA) is an immune-mediated, non-scarring hair loss disorder.1 Baricitinib, a selective Janus kinase 1 and 2 (JAK 1, 2) inhibitor, was the first approved therapy for adults with severe AA2 and has a well-established safety profile with safety data available through 104 weeks.3 In the BRAVE AA1/AA2 clinical trials, significantly more patients achieved a Severity of Alopecia Tool (SALT) score ≤20 (at least 80% scalp coverage) after 36 weeks of baricitinib, compared with placebo, treatment.4, 5 Increasing response rates after 36 weeks of treatment were observed, suggesting variability in regrowth rate and a need for longer treatment duration for some individuals.6 Furthermore, regrowth may not be the same across different hair-bearing sites.2 The present analysis evaluates long-term scalp hair regrowth in patients with severe AA treated with baricitinib 4 mg who achieved clinically meaningful eyebrow or eyelash (EB/EL) regrowth but not a SALT score ≤20 during the first 52 weeks of treatment. Patients randomized to baricitinib 2 mg were increased to 4 mg at Week 52 if they had a SALT score >20 and are not included in this analysis. Scalp hair loss was assessed using the SALT score4, 5 while EB/EL hair loss were measured using ClinRO EB/EL.7 In the BRAVE trials (pooled, N = 1200), of the 515 patients who were randomized to baricitinib 4 mg, 78 (15.1%) had EB/EL response (defined as ClinRO EB or EL scores of 0 or 1 with ≥2-point improvement) but not scalp response SALT score >20 at Week 52 (referred to as EB/EL/Scalp NR subgroup). Compared with the baricitinib 4 mg intent to treat (ITT) population, the EB/EL/Scalp non-responder subgroup showed higher mean baseline SALT scores (96.8 vs. 85.1), a greater proportion of patients with a baseline SALT score 95–100 (87.2% vs. 51.8%) classification of alopecia universalis (AU; 74.4% vs. 46.2%) and nail involvement (61.5% vs. 50.8%). At Week 52, the EB/EL/Scalp NR subgroup had a mean SALT score of 62.4 (median score 58.5; range, 22–100). After Week 52, some individuals in the EB/EL/Scalp NR subgroup started to achieve a SALT score ≤20, with 39% meeting this endpoint at Week 104 and 35% at Week 152 (Figure 1). The mean improvement in SALT score was 35% at Week 52, which increased to 56% by Week 104 and maintained through Week 152 (Figure 2). While it is uncertain if EB or EL regrowth is a conclusive predictor of later scalp hair regrowth, the present analysis shows that EB or EL regrowth precedes scalp hair regrowth for some patients, which informs treatment expectations. This was a preponderance of patients with AU in this subgroup, indicating that some of these patients are more likely to require longer than a year to reach SALT score ≤20.8 In summary, almost 40% of patients treated with baricitinib 4 mg who experienced meaningful eyebrow or eyelash regrowth but not SALT score ≤20 during the first year of treatment subsequently achieved SALT score ≤20 in the following year. The patients with a lag in scalp response generally had higher baseline severity. These results advance our understanding of AA and informs clinicians regarding therapy duration to optimize treatment responses in patients with severe AA and eyebrows and/or eyelashes involvement. Eli Lilly and Company would like to thank the clinical trial participants and their caregivers, without whom this work would not be possible. The authors would like to acknowledge Lucy May Gee Ph.D. for scientific writing expertise. This study was funded by Eli Lilly and Company. AM has received consulting fees from Hims and Hers, AbbVie, Equillium, ASLAN, apogee, Boehringer Ingelheim, Figure 1, ACOM, Olaplex. He has stock in Hims and Hers, and is secretary and treasurer for the Medical Dermatology Society. MA served as a consultant or paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of Alopecia areata including AbbVie, Almirall, Eli Lilly, Pfizer. KH has received research grants from Maruho, Taiho Pharma, Kaken Pharmaceutical, AbbVie, Sun Pharma, Eli Lilly and Pfizer, and served as a speaker for Eli Lilly, and Pfizer Japan. MS has served on advisory boards and/or is a consultant for Lilly, Pfizer, SUN Pharma, AbbVie, Inmagene and as a speaker for Lilly & Pfizer. YD, GY, SB, MM and JK are employees and shareholders of Eli Lilly and Company. YY is employed by TigerMed group and is contracted by Eli Lilly to perform statistical analysis. BK has served on advisory boards and/or is a consultant and/or is a clinical trial investigator and/or is on a Data Monitoring Committee for Abbvie, AltruBio Inc, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol-Meyers 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, Sun Pharmaceutical, TWi Biotechnology Inc, Viela Bio and Ventyx Biosciences Inc. He has served on speaker bureaus for Abbvie, Incyte, Eli Lilly, Pfizer, Regeneron and Sanofi Genzyme. He is a scientific advisor for BiologicsMD. These trials have been conducted in accordance with the ethical principles of the Declaration of Helsinki and followed Good Clinical Practice guidance. Protocols were approved by each centre's institutional review board or ethics committee. All patients in this manuscript have given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details for publication. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available upon request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data-sharing environment. For details on submitting a request, see the instructions provided at https://vivli.org/.