Immune Cell-Targeting Biologics for Alopecia Areata: A New Paradigm in Precision Medicine.

Background: Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with limited treatment options for severe disease. Although Janus kinase inhibitors have recently been approved, safety concerns remain, highlighting the need for alternative targeted therapies. Biologics that modulate immune cell activity may offer novel therapeutic avenues in AA. Summary: A review of peer-reviewed case reports, case series, and clinical trials evaluating immune cell-targeting biologics for AA, including rituximab, abatacept, alefacept, efalizumab, nivolumab, aldesleukin. Rituximab (anti-CD20) achieved complete remission in 1 patient with alopecia universalis. Abatacept (CTLA4-Ig) reduced mean SALT score by 71% in responders, though no response occurred in patients with extensive disease. Alefacept (anti-CD2 fusion) showed no significant improvement over placebo in a clinical trial, yet case reports documented up to 100% regrowth. Efalizumab (anti-CD11a) failed to improve SALT in a phase II trial, but individual cases achieved 70-100% regrowth. Nivolumab (PD-1 inhibitor) produced complete regrowth maintained beyond 1 year in a single case. Aldesleukin (low-dose IL-2) did not yield statistically significant efficacy in a clinical trial; however, a pilot study reported all patients experiencing hair regrowth along with improvements in quality of life. Across studies, adverse events were mild, with no serious events reported. Key Messages: (1) Biologics targeting B and T cells demonstrated moderate efficacy overall, suggesting that B-cell depletion and T-cell modulation may be viable strategies in AA, although better targets are needed to improve efficacy. (2) Abatacept showed partial regrowth in multiple patients, while alefacept, efalizumab, and aldesleukin were largely ineffective in controlled trials, despite several case-level responses. (3) Rituximab and nivolumab achieved complete regrowth in isolated cases, but evidence remains anecdotal.