Inebilizumab reduces the risk of flares in IgG4-related disease

1. In this randomized controlled trial, inebilizumab, an anti-CD19 monoclonal antibody, reduced the risk of flares and increased the likelihood of remission among patients with IgG4-related disease.

2. Adverse events and severe adverse events occurred more frequently in the inebilizumab group than in the placebo group in this limited 52-week trial.

Evidence Rating Level: 1 (Excellent)

Study Rundown: IgG4-related disease is a rare, chronic, immune dysfunction characterized by the growth of lesions rich in CD19+ B cells and marked by elevated levels of serum IgG4, resulting in inflammation and fibrosis involving many organ systems. This eventually leads to dysfunction and failure. Glucocorticoids can induce remission and prevent flare, but they do not provide disease control once tapered and are associated with many adverse events. Inebilizumab is a humanized monoclonal antibody that targets CD19 and induces deep B cell depletion. This trial investigated inebilizumab in patients with IgG4-related disease requiring glucocorticoid treatment. Compared to placebo, inebilizumab reduced the risk of flares and increased the likelihood of flare-free treatment-free complete remission at one year. Adverse events, including serious events and infections, were more common in the inebilizumab group. However, the study was not powered to predict the safety profile of inebilizumab. Despite its limited duration precluding complete safety assessment of B cell depletion, the study suggested that inebilizumab could lower the risk of flares and increase the likelihood of remission in patients with IgG4-related disease.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This was a randomized, placebo-controlled trial investigating inebilizumab for patients with IgG4-related disease. Adult patients were included who met the 2019 American College of Rheumatology/European League Against Rheumatism diagnostic criteria for IgG4-related disease, with at least two-organ involvement, and required glucocorticoid therapy for a current flare. Exclusion criteria included immunodeficiency, recent treatment with non-glucocorticoid immunosuppressants, severe hepatic or renal insufficiency, or history of a malignancy. In total, 135 patients were randomized 1:1 to receive either inebilizumab or a placebo for 52 weeks. The primary outcome was time to the first treated adjudicated disease flare requiring treatment, determined by comprehensive clinical assessment. Inebilizumab significantly reduced the risk of flares by 87% compared to placebo (hazard ratio, 0.13; 95% Confidence Interval [CI], 0.06-0.28; p<0.001). By week 52, 10% of patients in the inebilizumab group experienced flares as compared to 60% in the placebo group. The annualized flare rate was significantly lower with inebilizumab (rate ratio, 0.14; 95% CI, 0.06-0.31; p<0.001). Inebilizumab also significantly increased the likelihood of both flare-free, treatment-free complete remission (odds ratio [OR], 4.68; 95% CI, 2.21-9.91; p<0.001) and flare-free, glucocorticoid-free complete remission (OR, 4.96; 95% CI, 2.34-10.52; p<0.001) at week 52. In summary, these results showed that inebilizumab reduced disease flares and increased flare-free complete remission in IgG4-related disease.

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