John Stone, MD, Professor of Medicine at Harvard Medical School and Edward A. Fox Chair in Medicine at Massachusetts General Hospital, discusses data on rilzabrutinib in the treatment of IgG4-related disease (IgG4-RD).
IgG4-RD is an immune-mediated condition that can affect multiple organ systems. Common features include IgG4-related autoimmune pancreatitis, swelling within an organ system, salivary gland disease, swollen lymph nodes, skin manifestations, and symptoms consistent with allergies or asthma. The cause of IgG4-RD is unknown. Historically, the treatment of IgG4-RD has mainly consisted of the use of glucocorticoids.
Data from a phase 2 study evaluating the use of rilzabrutinib in treating patients with IgG4-RD was recently published at the 2025 European Alliance of Associations for Rheumatology (EULAR) Congress. The study discussed was a multicenter, open-label, two-arm, proof-of-concept, 52-week study that enrolled approximately 25 adult patients with active IgG4-RD. Rilzabrutinib is an oral, reversible Bruton’s tyrosine kinase inhibitor that targets the restoration of immune balance via multi-immune modulation.
Results observed included 70% of patients treated with rilzabrutinib were flare free at week 52 without additional treatments. Clinically meaningful improvements in disease activity were also seen at week 52 assessed by a 2-point or greater reduction in IgG4-RD responder index. IgG4-RD responder index reductions were seen as early as week 12 and sustained at week 52.
Additionally, the safety profile of rilzabrutinib was consistent with previous studies and no new safety signals were observed. Treatment-emergent adverse events were reported in 10% or greater of participants with the most common being diarrhea, COVID-19, dizziness, dry mouth, and nausea.
The U.S. Food and Drug Administration (FDA) has granted rilzabrutinib Fast Track Designation as well as Orphan Drug Designation for the treatment of IgG4-RD. A phase 3 clinical trial program is expected to start later in 2025.
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To learn more about IgG4-RD and other rare autoimmune conditions, visit https://checkrare.com/diseases/autoimmune-and-auto-inflammatory-disorders/