Placebo Response Model for Alopecia Areata: A Model-based Meta-analysis of Randomized Controlled Trials
Authors: Yan Diqin , Hu Dingyuan , Huang Fan , Fang Yi 
Published: February 2025

Objectives: As novel therapeutics have been extensively studied in alopecia areata (AA) randomized controlled trials (RCTs), a placebo is often used as control. The placebo response varied widely across different trials, and the influencing factors remained unknown. Therefore, a comprehensive understanding of the placebo response is crucial for guiding AA drug development. This study aimed to establish a placebo response model for AA and identify critical factors influencing placebo response. Methods: A systematic bibliographic search was conducted in PubMed, EMBASE and Cochrane library from inception to 29 April 2023. Randomized double-blind placebo-controlled trials of AA patients reporting percent change from baseline in Severity of Alopecia Tool (SALT) score were included by three reviewers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed for data extraction and risk of bias assessment. A model-based meta-analysis with a random-effects model was performed to quantitatively analyze the diachronic changes of placebo response and its associated factors. The primary end point was the time course of the placebo response on the percent change from baseline in SALT scores. Results: A total of 10 publications were included for analysis, comprising 573 subjects from 11 RCTs [1-10]. The final model accurately described the time-course characteristics of the percent changes from baseline in SALT score in placebo groups. The typical maximum (Emax) placebo response was 11.9%, with 15.5 and 51.6 weeks needed to reach 50% (ET50) and 90% (ET90) of this response, respectively. In subgroup analyses, the placebo responses demonstrated a significant association with gender and a potential association with AA subtypes and the current episode duration. Conclusions: The results suggested the effect of time on placebo response could not be neglected, and a higher placebo response could be observed in male AA patients without alopecia totalis (AT)/alopecia universalis (AU) and with a shorter duration of current episode of AA. The findings may provide a valuable reference for decision-making in drug development, clinical trial design, and clinical practice.The results in this abstract have been previously presented in part at the 9th International Symposium in Quantitative Pharmacology, held in Shanghai, China, from Oct 12-15, 2023.Citations: [1] King B, Guttman-Yassky E, Peeva E, et al. A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. Conference Paper. J Am Acad Dermatol. 2021;85(2):379-387. doi:10.1016/j.jaad.2021.03.050[2] King B, Ko J, Forman S, et al. Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: Phase 2 results from a randomized controlled study. Article. J Am Acad Dermatol. 2021;85(4):847-853. doi:10.1016/j.jaad.2021.05.050[3] King B, Ohyama M, Kwon O, et al. Two Phase 3 Trials of Baricitinib for Alopecia Areata. Article. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343[4] Mikhaylov D, Glickman JW, Del Duca E, et al. A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata. Article in Press. Archives of Dermatological Research. 2022;doi:10.1007/s00403-022-02336-0[5] Mikhaylov D, Pavel A, Yao C, et al. A randomized placebo-controlled single-center pilot study of the safety and efficacy of apremilast in subjects with moderate-to-severe alopecia areata. Article. Archives of Dermatological Research. 2019;311(1):29-36. doi:10.1007/s00403-018-1876-y[6] Nct. A Pilot Study of Tralokinumab in Subjects With Moderate to Severe Alopecia Areata. Trial registry record; Clinical trial protocol. https://clinicaltrialsgov/show/NCT02684097. 2016;[7] Nct. A Study of ATI-50002 Topical Solution for the Treatment of Alopecia Areata. https://clinicaltrialsgov/show/NCT03354637. 2017;[8] Nct. ATI-501 Oral Suspension Compared to Placebo in Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis. https://clinicaltrialsgov/show/NCT03594227. 2018;[9] Olsen EA, Kornacki D, Sun K, Hordinsky MK. Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study. Article. J Am Acad Dermatol. 2020;82(2):412-419. doi:10.1016/j.jaad.2019.10.016[10] Zhou C, Yang X, Yang B, et al. A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy and Safety of Ivarmacitinib (SHR0302) in Adult Patients with Moderate to Severe Alopecia Areata. J Am Acad Dermatol. Apr 3 2023;doi:10.1016/j.jaad.2023.02.063