CLINICAL QUESTION: Is inebilizumab a safe and effective treatment option for IgG4-related disease?
BACKGROUND: Treatment for IgG4-related disease flares currently involves glucocorticoid use and previously had no approved treatment specifically for IgG4-related disease.
STUDY DESIGN: Phase 3, randomized, parallel-cohort, double-blind, placebo-controlled trial
SETTING: 80 sites in 22 countries
SYNOPSIS: IgG4-related disease is an inflammatory process that involves initial CD19+ B cells aggregating together, followed by CD20+ B cells, which may lead to fibrosis of multiple organs. 5.3 persons per 100,000 in the U.S. have this diagnosis. Currently, glucocorticoids are used to prevent flares, but maintaining remission from IgG4-related disease is limited when steroids are weaned. Additionally, chronic steroid use places patients at risk for steroid-induced hyperglycemia and osteoporosis. The MITIGATE trial studied the efficacy and safety of inebilizumab, a human monoclonal antibody that targets CD19+ B cells, in patients with active IgG4-related disease affecting two or more organs. All patients took steroids for three to eight weeks and were weaned off steroids prior to randomization. Patients in the treatment arm received pre-treatment medication to prevent an infusion reaction. Patients received 300 mg of IV inebilizumab on day one, day 15, and at week 26.
Inebilizumab decreased IgG4-related disease flares by 87% (P <0.001). Annualized flare rates, or the number of disease flares over a year, were lower in those treated with inebilizumab (P <0.001), compared to the placebo group. Adverse events for inebilizumab participants included coronavirus, lymphopenia, and urinary tract infection.
BOTTOM LINE: Inebilizumab should be considered for the treatment of IgG4-related diseases as an alternative to steroids.
CITATION: Stone JH, et al. Inebilizumab for treatment of IgG4-related disease. N Engl J Med. 2025;392(12):1168-1177. doi:10.1056/NEJMoa2409712.
Dr. Ally
Dr. Ally is a clinical professor of medicine, a hospitalist in the division of hospital medicine, and a physician advisor at UC San Diego Health in San Diego.