INEBILIZUMAB, a CD19+ B-cell depleting therapy, can reduce flares and promote remission in patients with IgG4-related disease (IgG4-RD) according to the results of a new Phase III clinical trial. This chronic, relapsing immune-mediated condition affects multiple organs and currently has no approved therapies.
Methods
This multicenter, double-blind, placebo-controlled trial included 135 adults with active IgG4-related disease. Participants were randomized 1:1 to receive either inebilizumab (300 mg intravenously on Days 1 and 15 and again at Week 26) or placebo over a 52-week treatment period. Both groups adhered to an identical glucocorticoid tapering protocol. While glucocorticoids were permitted for managing disease flares, other background immunosuppressants were excluded.
The trial’s primary endpoint assessed the time to the first treated, adjudicated disease flare during the treatment period. Secondary endpoints included the annualized flare rate and rates of treatment-free and glucocorticoid-free complete remission.
Results
Inebilizumab demonstrated superior outcomes compared to placebo. In the inebilizumab group, only 7 participants (10%) experienced at least one flare, compared to 40 participants (60%) in the placebo group, representing a hazard ratio of 0.13. The annualized flare rate was also lower with inebilizumab.
Additionally, inebilizumab-treated participants were significantly more likely to achieve flare-free, treatment-free complete remission and glucocorticoid-free remission. However, the study also reported serious adverse events in 18% of participants in the inebilizumab group compared to 9% in the placebo group. These results highlight the efficacy of inebilizumab in targeting CD19+ B cells, offering a therapeutic pathway for IgG4-related disease.
Reference: Stone JH et al. Inebilizumab for treatment of IgG4-related disease. NEJM. 2024. DOI: 10.1056/NEJMoa2409712.
