IgG4-Related Disease: Navigating Diagnosis and the Expanding B-Cell-Targeted Treatment Landscape - Episode 13
Anti-CD19 B-Cell Depletion in IgG4-RD: Phase 3 Data and Practice
The first phase 3 trial in IgG4-related disease showed an unusually strong reduction in flares with anti-CD19 B-cell depletion. The panel reviews the design, safety signals, and early clinical experience.
This episode, "Anti-CD19 B-Cell Depletion in IgG4-RD: Phase 3 Data and Practice," features the panel reviewing a landmark trial and its translation into everyday care.
Dr. Katz describes MITIGATE as the first registrational phase 3, randomized, double-blind, placebo-controlled trial in IgG4-related disease. It evaluated inebilizumab, an anti-CD19 monoclonal antibody, and led to the first FDA approval in this disease. Patients met the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria. They had active new or relapsing disease involving at least 2 organs. All received glucocorticoids during screening. From baseline, prednisone 20 mg was tapered to zero over 8 weeks. The primary outcome was flare over 52 weeks.
Results were overwhelmingly positive, Dr. Katz says, with a hazard ratio of 0.13. He calls it one of the most positive trials in rheumatology history. All key secondary outcomes were met, including annualized flare rate and glucocorticoid use. Infections, particularly COVID-19, were numerically more frequent with inebilizumab. Serious adverse events, largely infections, were also numerically higher. He weighs this against a substantial reduction in cumulative glucocorticoid exposure.
Dr. Della Torre, a trial investigator, was impressed by the near absence of relapses. The results confirm what clinicians have seen with anti-CD20 therapy. Targeting CD19 may reach a broader range of B cells, including autoreactive naive cells, plasmablasts, and some plasma cells. The trial also showed that remission can be reached within about 2 to 3 months without added glucocorticoid toxicity. He hopes to see whether broader B-cell targeting reduces relapse over the longer term.
In clinic, Dr. Katz uses inebilizumab as much as he previously used rituximab. Patients on rituximab maintenance or presenting with relapse can choose whether to switch. Many switch because inebilizumab infusions are much shorter. He now treats most newly diagnosed patients with inebilizumab, with few infusion reactions. He sees no major efficacy difference between the two; both reliably induce remission.
Up next, in "B-Cell Inhibition in IgG4-RD: Phase 3 Trial Design and Outcomes," Dr. Della Torre introduces a different strategy: inhibiting B cells rather than depleting them.
