#5-24E. Targeting BTK in IgG4-Related Disease: A Steroid-Sparing Breakthrough (Ann Rheum Dis, 2026)

Are you looking for a way to manage IgG4-related disease without the burden of long-term glucocorticoid toxicity or persistent B-cell depletion? This Phase 2a open-label study evaluated rilzabrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, in twenty-seven patients undergoing a rapid glucocorticoid taper. Remarkably, seventy point four percent of participants remained entirely flare-free and off steroids or immunosuppressants at the end of the fifty-two-week treatment, achieving significant sustained reductions in disease activity and serum IgG4 levels. This represents a groundbreaking milestone, demonstrating for the first time that selective BTK inhibition can achieve profound clinical and serological improvement without depleting B cells. However, when critically appraising these findings, we must note that the study’s open-label design, lack of a placebo control, and small sample size of twenty-seven patients limit its generalizability. Nevertheless, for clinicians, this trial is highly significant as it introduces a novel, non-B-cell-depleting oral alternative that avoids the infectious and vaccine-unresponsive risks of traditional therapies, potentially redefining our daily management of IgG4-related disease.

Citation: John H. Stone, Mollie Carruthers, Matthew C. Baker, et al. A phase 2 trial of rilzabrutinib in IgG4-related disease. Annals of the Rheumatic Diseases. 2026. DOI: 10.1016/j.ard.2026.05.017

URL: https://doi.org/10.1016/j.ard.2026.05.017

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