Inebilizumab improves outcome in patients generalized myasthenia gravis

1. In patients with myasthenia gravis (MG) who had anti-acetylcholine receptor antibodies or anti-muscle-specific kinase antibodies, intravenous inebilizumab reduced disease severity and improved function compared to placebo.

2. Inebilizumab had an acceptable safety profile consistent with trials in conditions other than MG and was not associated with increased severe adverse events. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: MG is an autoimmune disorder where auto-antibodies affecting post-synaptic neuromuscular transmission, including acetylcholine receptors (AchR) and muscle-specific kinase (MSK), are produced by CD19+ B-cells, resulting in fluctuating muscle weakness. Current therapies include glucocorticoids, cholinesterase inhibitors, thymectomy, and long-term immunosuppression. Rituximab, a CD20 B-cell depletion therapy, has shown variable efficacy in trials, possibly because CD19+/CD20- B-cells are involved in MG pathophysiology. Inebilizumab is a novel CD19+ B cell-depleting monoclonal antibody. This trial investigated inebilizumab in treating MG patients with positive anti-AchR and anti-MSK antibodies, with all patients undergoing glucocorticoid taper concurrently. By week 26, inebilizumab resulted in a greater reduction in disease activity scores from baseline compared to placebo in the combined antibody population. These results were also seen within patient subpopulations separated by anti-AchR and anti-MSK antibody status, respectively. Inebilizumab was associated with headache, cough, nasopharyngitis, and urinary tract infections, but not higher risk of serious adverse events. Although this trial was limited in its length, it demonstrated the promise of inebilizumab in reducing disease activity and improving activities of daily living in patients with MG with anti-AchR and anti-MSK antibodies.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This was a placebo-controlled trial assessing the efficacy and safety of inebilizumab in the treatment of MG. Patients 18 years of age or older, who were diagnosed with generalized MG, tested positive for either anti-AchR or anti-MSK antibodies, had a MG Activities of Daily Living score (MG-ADL) ≥11 or between 6-10 (with >50% attributed to non-ocular items), a Quantitative Myasthenia Gravis score ≥11, and had been receiving a stable dose of glucocorticoids or non-steroidal immunosuppression were eligible for inclusion. In total, 238 patients were randomized 1:1 to receive either intravenous inebilizumab 300mg on days 1 and 15 (for all patients in the inebilizumab group) or placebo. The primary outcome was the change from baseline in the score on the MG-ADL at week 26 in the combined anti-AchR and anti-MSK antibody population. By week 26, patients in the inebilizumab group had a greater reduction in the MG-ADL score than those who received placebo at week 26: least-squares mean change -4.2 for inebilizumab vs. -2.2 for placebo (Adjusted Difference [AD], -1.9; 95% Confidence Interval [CI], -2.9 to -1.0, p<0.001). Similar findings were noted in the 26-week QMG score, where the least-squares mean change from baseline was -4.8 for inebilizumab and -2.3 for placebo (AD, -2.5; 95% CI, -3.8 to -1.2; p<0.001). These trends were also observed for the 26-week MG-ADL score in the anti-AchR (AD, -1.8; 95% CI, -2.9 to -0.7; p<0.002) and anti-MSK (AD, -2.2; 95% CI, -4.2 to -0.2; p=0.03) subpopulations, as well as QMG score. The most common adverse events with inebilizumab were headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections. Inebilizumab was not associated with a higher incidence of serious adverse events. Immune complex disease, cytopenia, and serious and opportunistic infections occurred in a small number of inebilizumab recipients. In summary, these results showed that inebilizumab improved daily activity and reduced disease severity in patients with generalized MG, while maintaining a tolerable safety profile.

Image: PD

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