#2-60E. Targeting Refractory GPA: Mosunetuzumab, a Novel T-Cell Engager (ARD, 2025)

How should we approach severe granulomatosis with polyangiitis (GPA) that is refractory to standard B-cell depletion therapy, such as rituximab (RTX)? This letter addresses the crucial need for more efficient treatment strategies in RTX-refractory cases, which often still require glucocorticoids for a sufficient response1. We discuss the first reported application of a bispecific CD20xCD3 T-cell engager (TCE), mosunetuzumab—a drug currently approved for lymphoma—in an autoimmune vasculitis. This is a histology-guided case report concerning a patient with relapsing refractory GPA who previously failed RTX and cyclophosphamide treatments. The most striking finding is that mosunetuzumab induced complete clinical and serological remission safely and effectively without the concomitant use of glucocorticoids. This success suggests a novel and highly potent mechanism for CD20-targeting therapy, particularly where conventional B-cell depletion is limited by the disease's granuloma architecture. While this exciting result provides a glimpse into a new therapeutic avenue for refractory GPA, clinicians must critically consider the inherent limitation of it being a single-case report, underscoring the necessity for robust future trials. This case offers vital insights for physicians managing complex autoimmune vasculitis, potentially broadening the therapeutic armamentarium.

Citation: Stutz AN, Lahu LM, Jaschinski S, et al. Mosunetuzumab, a CD20xCD3 bispecific T-cell engager, in granulomatosis with polyangiitis. Annals of the Rheumatic Diseases. 2025. DOI: 10.1016/j.ard.2025.10.026

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