Positioning B-Cell Depletion and B-Cell Inhibition in IgG4-RD Care

"Positioning B-Cell Depletion and B-Cell Inhibition in IgG4-RD Care" takes up the question of how two distinct B-cell strategies may divide the treatment landscape.

Dr. Katz, also an INDIGO investigator, calls the trial overwhelmingly positive. He notes, however, that obexelimab did not show the near-universal efficacy seen with B-cell depletion. He believes aspects of the trial design partly explain that difference. He views B-cell inhibition as a middle ground between no treatment or glucocorticoids alone and B-cell depletion. He hopes it will deliver most of the disease control of depletion with fewer long-term risks.

Reversibility is central to that hope. Long-term data are still needed. If obexelimab avoids hypogammaglobulinemia and other consequences of prolonged depletion, Dr. Katz expects a potential paradigm shift in maintenance therapy. A safer long-term option would be very attractive.

Asked about conventional immunosuppressants such as mycophenolate and cyclophosphamide, Dr. Katz says he rarely uses them. Their efficacy is more variable and their side effects greater than those of B-cell-targeted therapies. If obexelimab gains FDA approval, he plans to discuss its risks and benefits against depletion with many patients. Some will prefer subcutaneous injections and others infusions. Some will want a drug that almost guarantees remission rather than one with a high, but less certain, likelihood.

For the rare patient with extremely active multi-organ disease and catastrophic risk, Dr. Katz would still choose B-cell depletion. Most patients, however, could reasonably receive either. He is also considering inducing remission with depletion and maintaining it with B-cell inhibition. No data yet support this strategy, and he would like to see it studied.

Dr. Della Torre agrees. More drugs will allow clinicians to tailor therapy to comorbidities again. A drug that can be withdrawn after side effects is reassuring. Broader B-cell depletion is also valuable. Dr. Culver adds that reversibility may suit patients with poor vaccine responses or high infection risk.

In "Emerging IgG4-RD Therapies: Cellular, Oral, and Pathway-Targeted Approaches," both panelists will look past current options to the therapies now moving through development.