IgG4: Rare, but new treatments on the horizon

Janet Pope, MD, MPH, FRCPC

Oct 29, 2025 8:39 am

IgG4 is a rare autoimmune disease with excessive IgG4 immunoglobulins that can affect multiple organs yielding plasma cell deposition (inflammation) and fibrosis.

There has been great progress in treatment. Traditionally, glucocorticoids were used and if ineffective, then an oral immunesuppressive (ex: Azathioprine, MMF) and, if needed, rituximab. Many patients can improve sufficiently on this regimen.

However, there are now new drugs potentially that can be used.

Inebilizumab has recently been FDA approved due to a positive RCT (MITIGATE). This is a humanized mAb CD19 depleting drug. It was superior with glucocorticoids to glucocorticoids + placebo.

Obexelimab is another CD19 B cell depleter and is in phase 3 (INDIGO).

Two BTKi are being studied and there were some positive data (small N) presented for both Rilzabrutinib and Zanubrutinib.

There was a positive RCT of Tofacitinib vs placebo added to glucocorticoids in each group that was positive in clinical outcomes and IgG4 was reduced in the Tofa patients (N=58).

Other potential treatments have been described or are in studies:

Elotuzumab (mAb against SLAMF7 on T and B cells)
Belimumab (inhibits B cell signalling through BLyS)
Baricitinib (JAKi)
Stapokibart (IL4Ri)
CAR-T

Soon there may be more treatment options for your patients – but the hard work is recognizing them in clinical practice; and don’t be fooled by only having an IgG4 elevated level – get a tissue biopsy.

Abstract references:

0239: Safety of Rilzabrutinib, a BTK Inhibitor, in Adult Patients with IgG4-related disease (IgG4-RD) in a 52-week Phase 2 Open-label Study
1163: Clinical and Biomarker Characteristics of Inebilizumab-Treated Participants Who Experienced an IgG4-RD Flare During the Phase 3 MITIGATE Trial
1172: A Phase II, Single-Site, Open-Label Study of Zanubrutinib in Patients with IgG4-Related Disease
LB02: Tofacitinib Plus Glucocorticoids Can Effectively Reduce Relapse Rate in IgG4-Related Disease: A Randomized,Open-label controlled Trial