Anti-CD19 Inebilizumab in Managing Myasthenia Gravis
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on July 7th, 2025
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Myasthenia gravis is an autoimmune disease in which B cells produce antibodies targeting the acetylcholine receptor at the neuromuscular junction. The disease can be managed by anti-inflammatory glucocorticoid and cholinesterase inhibitors to increase the signal duration at the neuromuscular junction. Targeting the B-cells producing autoantibody is another option with rituximab targeting the CD20 marker on B-cells. Inebilizumab is another viable option that targets another marker on B-cells. Amgen had sponsored a study to evaluate its effectiveness in managing myasthenia gravis.
The phase 3 clinical study included 238 participants who had been diagnosed with generalized myasthenia gravis and with blood work positive for either anti-acetylcholine receptor antibodies or anti-muscle-specific kinase antibodies. Assessment with the MG-ADL scale yields an average score of 9.1, with the higher score meaning more dilapidating disease. The MG-ADL scale ranges from 0 to 24, and it evaluates the disease’s effect on daily life activity such as chewing, swallowing, brushing teeth, etc.. Glucocorticoid is the most commonly used immunosuppressive treatment with 93% of the participants treated with a mean daily dose of 17.5 mg.
The patients were randomly assigned to be treated with either 300 mg of inebilizumab or placebo. The treatment was administered intravenously on day 1 and 15 of the study; for patients with autoantibodies targeting acetylcholine receptors, an additional dose was delivered on day 183. Compared to other anti-B cell therapy of rituximab, inebilizumab targets the CD19 surface marker instead of CD20. Targeting CD19 might be more effective as B-cell downregulates CD20 expression as it matures while CD19 expression is kept constant.
Assessment 365 days after the first treatment found that inebilizumab was more effective than placebo at managing myasthenia gravis as patients treated with inebilizumab experienced a 4.2 reduction on the MG-ADL scale. Evaluations with the QMG scale also report the same clinical improvement. This beneficial effect is observable in patients with autoantibodies targeting the neuromuscular junction acetylcholine receptor and those with autoantibodies against muscle-specific kinase. Adverse effects analysis found that inebilizumab increased the frequency of nasopharyngitis and urinary tract infection; however, none of the side effects was serious. Researchers noted that the trial length is not sufficient to study the long-term effect of inebilizumab, and a longer open-label trial is needed.
The phase 3 clinical study included 238 participants who had been diagnosed with generalized myasthenia gravis and with blood work positive for either anti-acetylcholine receptor antibodies or anti-muscle-specific kinase antibodies. Assessment with the MG-ADL scale yields an average score of 9.1, with the higher score meaning more dilapidating disease. The MG-ADL scale ranges from 0 to 24, and it evaluates the disease’s effect on daily life activity such as chewing, swallowing, brushing teeth, etc.. Glucocorticoid is the most commonly used immunosuppressive treatment with 93% of the participants treated with a mean daily dose of 17.5 mg.
The patients were randomly assigned to be treated with either 300 mg of inebilizumab or placebo. The treatment was administered intravenously on day 1 and 15 of the study; for patients with autoantibodies targeting acetylcholine receptors, an additional dose was delivered on day 183. Compared to other anti-B cell therapy of rituximab, inebilizumab targets the CD19 surface marker instead of CD20. Targeting CD19 might be more effective as B-cell downregulates CD20 expression as it matures while CD19 expression is kept constant.
Assessment 365 days after the first treatment found that inebilizumab was more effective than placebo at managing myasthenia gravis as patients treated with inebilizumab experienced a 4.2 reduction on the MG-ADL scale. Evaluations with the QMG scale also report the same clinical improvement. This beneficial effect is observable in patients with autoantibodies targeting the neuromuscular junction acetylcholine receptor and those with autoantibodies against muscle-specific kinase. Adverse effects analysis found that inebilizumab increased the frequency of nasopharyngitis and urinary tract infection; however, none of the side effects was serious. Researchers noted that the trial length is not sufficient to study the long-term effect of inebilizumab, and a longer open-label trial is needed.