In the MITIGATE trial, inebilizumab-cdon (Uplizna) reduced the risk of immunoglobulin G4–related disease flares by 87% compared with placebo in adult patients.

Based on data from the study, the FDA approved inebilizumab as the first and only treatment for adults with immunoglobulin G4–related disease (IgG4-RD), a chronic, immune-mediated fibroinflammatory condition affecting multiple organ systems. The MITIGATE trial was the first randomized, double-blind, placebo-controlled study in this patient population.

During the 52-week placebo-controlled period, inebilizumab significantly reduced the risk of IgG4-RD flares by 87% compared with placebo (hazard ratio = 0.13; P < .001). Flare-free, corticosteroid-free, complete remission at week 52 was achieved in 58.8% of patients treated with inebilizumab vs 22.4% of those receiving placebo (P < .001). The annualized flare rate was 0.10 for those receiving inebilizumab vs 0.71 for those receiving placebo (P < .001). Additionally, 89.7% of patients in the inebilizumab group required no glucocorticoids beyond the planned taper, and mean total glucocorticoid exposure was reduced ten-fold compared with placebo (118 mg vs 1,385 mg).

Inebilizumab is a humanized monoclonal antibody that targets CD19+ B cells, including plasmablasts and some plasma cells, which are believed to contribute to disease pathogenesis in IgG4-RD. The mechanism by which inebilizumab exerts its effect in IgG4-RD has not been fully established. After two loading doses, the treatment is administered as a single infusion every 6 months.

The most common adverse events observed in the inebilizumab cohort were lymphopenia (19%) and urinary tract infection (12%). Infusion reactions occurred in 7.4% of patients, most commonly with the initial dose. The safety profile was consistent with prior data in other indications for the agent; inebilizumab is also FDA-approved for the treatment of neuromyelitis optica spectrum disorder in adults who are anti–aquaporin-4 antibody positive, and regulatory submissions are underway for the treatment of generalized myasthenia gravis.

According to the manufacturer, Amgen, ongoing efforts include increasing awareness of IgG4-RD to support earlier diagnosis and access to treatment. The variable and relapsing nature of IgG4-RD can resemble other conditions, which may complicate recognition and delay diagnosis.

Reference: Amgen. Uplizna® (inebilizumab-cdon) is now the first and only FDA-approved treatment for IgG4-related disease [news release].