Disease Duration Among Patients Recruited to Alopecia Areata Clinical Trials: A Systematic Review

To the Editor,

Alopecia areata (AA) is an immune-mediated hair disorder. ¹ A challenge in AA management is deciding when to initiate systemic treatment, as spontaneous regrowth is possible and future disease course remains uncertain. ² However, accumulating evidence suggests that disease duration (DD) is an underrecognized predictor of treatment response. ¹ This review examines DD among participants in phase II/III AA trials and evaluates associations with treatment response.

MEDLINE and Embase were searched from January 2015 to August 2025 using keywords related to “alopecia areata” and “Phase II/III” (Table S2). The study was registered on PROSPERO (CRD420251078784). Of 815 records initially identified, 7 full-text English language articles describing 8 completed phase II/III clinical trials evaluating emerging AA treatments were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools (Figure S1, Tables S2, S3, and S4). Exclusion criteria included incomplete trials, secondary analyses, paediatric trials, and other hair loss types.

A total of 2815 patients with AA were identified (Tables S1, S5, and S6). Most patients were female (63.1%) with a mean age of 36.8 ± 2.4 years. Mean baseline Severity of Alopecia Tool (SALT) score was 82.7 ± 7.0. Ethnoracial groups were white (63.2%), Asian (21.4%), black (8.6%), and other/unknown race (6.6%). Trials were primarily multinational (n = 6). Eight clinical trials reported flare duration (mean duration at baseline, 3.3 ± 0.7 years). Mean DD, when reported, was 11.2 ± 1.9 years (n = 5 clinical trials). Trials reporting DD <5 years (n = 2 clinical trials) or <2 years (n = 1 clinical trial) were less common. Across trials, eligibility criteria prioritized flare duration while total DD was rarely analyzed (Table S8). Furthermore, DD was rarely reported in post-hoc analyses (Table S9).

Shorter DD and flare duration were associated with better treatment response in AA (Tables S7 and S8).^3-5 A cohort study found that AA patients with shorter DD (<4 years) were significantly more likely to respond to baricitinib, with 63% achieving SALT ≤20, compared with 17% of those with 4 to 10 years’ DD (P = .042) and 22% with >10 years’ DD (P = .041). ³ Another cohort study examining baricitinib showed that 68.4% of patients with <4 years’ flare duration achieved SALT ≤20, compared with 30.8% of those with >4 years of flare duration (P < .05). ⁴ Similarly, post-hoc analyses of the ALLEGRO-IIb/III trials showed that early ritlecitinib responders had lower mean DD and flare duration (8.7 and 2.3 years) compared with nonresponders (11.1 and 4.1 years). ⁵

Data from our review point to the potential benefits of early intervention in AA. Despite this, most patients recruited to trials have long-standing disease, with trials requiring a flare duration of ≥6 months to be eligible. Studying long-DD patients may miss benefits of early intervention. To define if there is an ideal “window of opportunity” for disease-modifying treatment, future trials should recruit short-DD patients, stratify outcomes by DD, and assess DD-related predictors or confounders (eg, age, sex). This may clarify whether an early “top-down” approach, such as earlier initiation of systemic disease-modifying therapies, is more effective. This study is limited by exclusion of conference proceedings, abstracts, non-English, paediatric, and unpublished trials.