Inebilizumab, a CD19-directed antibody, has demonstrated efficacy in preventing flares in patients with Immunoglobulin G4-related disease (IgG4-RD), according to results from the MITIGATE trial. This international, prospective, double-blind, placebo-controlled study evaluated the safety and efficacy of B-cell depletion for flare prevention in IgG4-RD, a debilitating multiorgan disease characterized by recurring flares leading to organ dysfunction and decreased quality of life.
The MITIGATE trial (NCT04540497) was designed by an international panel of physicians with expertise in IgG4-RD. The study enrolled participants across 22 countries and aimed to accrue 39 flares to achieve sufficient power to detect a relative risk reduction of 65% in the inebilizumab group. A total enrollment of 160 participants was anticipated to achieve this goal.
Trial Design and Endpoints
The primary efficacy endpoint was the time from randomization to the occurrence of the first centrally adjudicated and investigator-treated disease flare during the 1-year randomized controlled period. Novel, organ-specific flare diagnostic criteria were developed specifically for this trial, incorporating symptoms and signs, laboratory findings, imaging study results, and pathology data. Secondary endpoints included safety, annualized flare rate, flare-free complete remission, quality-of-life measures, and cumulative glucocorticoid use.
Clinical Significance
IgG4-RD often requires treatment with glucocorticoids, which are associated with substantial treatment-related toxicity. Inebilizumab offers a potential alternative by mediating the rapid and durable depletion of CD19+ B cells, thought to be involved in IgG4-RD pathogenesis. The results of the MITIGATE trial provide insights into the natural history and pathophysiology of IgG4-RD and the efficacy and safety of B-cell depletion as a therapeutic avenue. The study represents a significant advancement in the treatment of IgG4-RD, offering a potential new therapeutic option for patients who may not tolerate or respond well to glucocorticoids.
