Study: Inebilizumab Reduces Flares and Improves Remission in IgG4-Related Disease

In a phase 3 randomized controlled trial, researchers evaluated inebilizumab, a monoclonal antibody targeting CD19+ B cells, for its efficacy and safety in treating immunoglobulin G4-related disease (IgG4-RD). This condition is a relapsing, multiorgan fibroinflammatory disorder with no currently approved treatments.

Given the role of CD19+ B cells in the pathophysiology of IgG4-RD, this study aimed to identify the safety and efficacy of inebilizumab as a targeted therapeutic approach to modulate disease activity and improve remission rates.

In this multicenter trial, 135 adults with active IgG4-RD were randomized to receive either 300-mg intravenous infusions of inebilizumab on days 1 and 15 and at week 26, or placebo. Both groups underwent identical glucocorticoid tapering protocols, and disease flares were managed with glucocorticoids as needed. The primary endpoint was the time to the first treated, adjudicated flare during the 52-week treatment period. Secondary endpoints included the annualized flare rate and rates of treatment-free and glucocorticoid-free complete remission.

Over a 52-week period, 10% of patients in the inebilizumab group experienced at least one disease flare compared with 60% in the placebo group (hazard ratio [HR] = 0.13; 95% CI, 0.06-0.28; P < .001). The annualized flare rate was significantly lower in the inebilizumab group (rate ratio = 0.14; 95% CI, 0.06-0.31; P < .001). Inebilizumab also improved the odds of achieving treatment-free complete remission (odds ratio [OR] = 4.68; 95% CI, 2.21-9.91; P < .001) and glucocorticoid-free complete remission (OR = 4.96; 95% CI, 2.34-10.52; P < .001). Serious adverse events occurred in 18% of the inebilizumab group compared to 9% of the placebo group, but these events were not specified as being directly linked to inebilizumab.

The study’s limitations include the relatively small sample size, which may not accurately predict the safety or efficacy of inebilizumab when given to a larger number of patients. Additionally, the median disease duration in the trial population was short. Longer-term data regarding disease duration may be needed to fully assess the durability of remission and long-term safety of inebilizumab.

“Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease,” the study authors concluded.

Reference

Stone JH, Khosroshahi A, Zhang W, et al. Inebilizumab for treatment of IgG4-related disease. N Engl J Med. Published online November 14, 2024. doi:10.1056/NEJMoa2409712