Abstract

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune condition that causes non-scarring hair loss and often leads to significant psychosocial distress. Although Janus kinase (JAK) inhibitors such as tofacitinib are effective, relapse after stopping treatment remains a major challenge. New evidence indicates that low-dose interleukin-2 (IL-2) may help maintain remission by increasing regulatory T cells, which can restore immune tolerance. OBJECTIVE: This proof-of-concept study aimed to evaluate the efficacy of sequential immunotherapy combining tofacitinib and low-dose IL-2 in inducing sustained remission for AA patients after treatment withdrawal. METHODS: A monocentric, retrospective case series was conducted at Xiangya Hospital, China, from September 2022 to May 2025. The IL-2 regimen comprised subcutaneous injections (0.5-1 million IU/day for 5 consecutive days per cycle), repeated every 3 weeks for two to three cycles. Tofacitinib was tapered and discontinued post-IL-2 therapy. Clinical outcomes, including relapse-free survival and safety, were monitored longitudinally. RESULTS: Four refractory AA patients (median follow-up: 32.5 months) with complete hair regrowth (SALT = 0) after ≥6 months of tofacitinib received adjunctive IL-2. Three patients maintained complete remission for 11-20 months after treatment cessation, while one experienced localized recurrence at 5 months but achieved control with low-dose tofacitinib maintenance. No adverse events were reported. CONCLUSION: Sequential tofacitinib and low-dose IL-2 therapy may reestablish immune tolerance, offering a potential strategy for drug-free remission. Larger trials are needed to confirm efficacy and optimize protocols.