Emerging IgG4-RD Therapies: Cellular, Oral, and Pathway-Targeted Approaches

In "Emerging IgG4-RD Therapies: Cellular, Oral, and Pathway-Targeted Approaches," our experts look ahead to the next generation of treatment options.

Dr. Culver asks which emerging therapies most interest the panel. Dr. Della Torre says that, as an immunologist, he is excited by agents that modulate B-cell and immune-cell activation. He cautions that treating patients is not a game. Clinicians must weigh the potential side effects of every new agent carefully. Several molecules are nearly ready, he notes. Some are oral, others infused, and some use chimeric antigen receptor T-cell strategies.

He also hopes research will uncover new pathogenic pathways. B-cell depletion has been used for nearly 20 years. He believes the field now has the capability to explore disease pathogenesis more deeply. New discoveries could improve, tailor, and personalize treatment.

Dr. Katz calls this a very exciting time for the field and for patients. Many therapies are in development. He would love to stop telling patients with active disease that only one drug is available. Each new agent will differ in risk profile, tolerability, mechanism of action, and route. Having those choices will give patients a larger role in their own care.

He also cares for many patients with IgG4-related disease and another autoimmune disease. Managing both is difficult on B-cell depletion, because he avoids layering additional immunosuppressants on top. Therapies that address more than one disease would be valuable. Cellular therapies excite him too, despite substantial toxicity. Their appeal is the theoretical possibility of a cure. If a cellular therapy eliminated disease-causing B cells or the entire B-cell compartment, short-term toxicity might be worthwhile. He stresses that this remains hopeful thinking without supporting data.

Dr. Culver summarizes the vision as early risk stratification, relapse markers, and treatment chosen for each patient. She lists cell-based therapies, T-cell engagers, and cytokine-directed agents. Future therapy may target allergic, inflammatory, or fibrotic phenotypes, sometimes in combination.

The next episode in this series, "Long-Term Monitoring in IgG4-RD: Imaging, Serology, and Visit Frequency," features Dr. Katz describing how he monitors patients over years of follow-up.