A phase 2 trial of rilzabrutinib in IgG4-related disease.

Publication date: Jul 21, 2026

The objective of the article is to assess the efficacy and safety of rilzabrutinib, an oral, reversible inhibitor of Bruton’s tyrosine kinase, in participants with IgG4-related disease. This Phase 2a (NCT04520451) open-label, 52-week study enrolled 2 cohorts of participants with IgG4-related disease: Cohort A (participants who had failed or were intolerant to rituximab) and Cohort B (participants enrolled agnostic to rituximab history). Participants received rilzabrutinib plus a 2-to-4-week glucocorticoid (GC) taper followed by rilzabrutinib alone for up to 52 weeks. Primary endpoints were the proportion of participants without disease flare following first rilzabrutinib dose until the end of treatment and safety. This study included 27 participants (Cohort A: 13; Cohort B: 14). At the end of treatment, 70. 4% (19/27) of participants were flare-free and off GCs/immunosuppressants. Disease activity (mean [SD]), measured by IgG4-related disease Responder Index, decreased by 8. 3 (5. 8) at week 12 in both cohorts and by 10. 7 (6. 3) in participants who completed 52 weeks of rilzabrutinib (14/17). Serious treatment-emergent adverse events (TEAEs) occurred in 2 participants, 1 resulting in death, but both events were judged unrelated to the study drug. The most frequent TEAEs were diarrhoea, 40. 7% (11/27); coronavirus disease 2019, 18. 5% (5/27); and dizziness, 18. 5% (5/27). Rilzabrutinib had an acceptable safety profile in patients with IgG4-related disease who had failed/ intolerant to rituximab and who were rituximab-nacEFve. Most participants discontinued GCs successfully without disease flares and exhibited sustained disease activity reduction. Further investigation of this potential alternative to B-cell-depleting therapies is needed in larger, long-term, placebo-controlled trials.

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