A Case Series Shows Long-Term Efficacy and Convenience of Ravulizumab in Generalized Myasthenia Gravis

A case series of 3 patients with generalized myasthenia gravis (MG) demonstrated the long-term efficacy of convenient infusion intervals of ravulizumab (Ultomiris; AstraZeneca), an FDA-approved terminal compliment C5 inhibitor for adults who are antiacetylcholine receptor (AChR) antibody positive, in symptom reduction and stability. These results suggest ravulizumab shows promise as a chronic treatment for patients with this condition who were previously on concomitant immunomodulators.¹

Among the 3 patients with MG treated with ravulizumab, findings showed that patients had extended their infusion intervals to 7 or 8 weeks, which were symptom-free. Results also revealed that ravulizumab stabilized symptoms and improved Myasthenia Gravis–Activities of Daily Living (MG-ADL) scores. Although patients had decreased exacerbations and showed no signs of significant adverse effects (AEs), authors recommended continuous monitoring while on the treatment.

Top Clinical Takeaways

Ravulizumab, administered at 7-to-8–week intervals, demonstrated efficacy in stabilizing symptoms and reducing exacerbations in three generalized myasthenia gravis patients.
The case series highlights significant improvement in MG-ADL scores and symptom reduction after switching to ravulizumab, suggesting its efficacy as a chronic treatment option.
Continuous monitoring is recommended for patients on ravulizumab, even though the study reported no significant adverse effects, emphasizing the need for vigilance during long-term treatment.

The findings were presented as a poster at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 3-6, in Orlando, Florida, by senior author Raam Sambandam, MD, neurologist at Synapse Neurology, and colleagues. In this case series, investigators retrospectively reviewed the long-term impact of ravulizumab in patients with MG who received concomitant immunomodulatory treatments.

In the first case, a 38-year-old woman with AChR antibody-positive generalized MG presented with ocular predominant, nonthymoma, with acute exacerbations of right eye ptosis. Diagnosed in 2016, the patient also displayed worsening limb weakness and shortness of breath. Previously, the patient had been treated with prednisone, mycophenolate, azathioprine, immunoglobulins, and efgartigimod (Vyvgart; Argenx). Following treatment with ravulizumab, the patient experienced symptom reduction, with an improvement observed on the MG-ADL score ranging from 8 to 5, and Morse Fall Scale ranging from 60 to 15. In addition, investigators reported no exacerbations observed at the 8-month follow-up after initiation of ravulizumab treatment with pyridostigmine extended-release dosage of 180 mg in May 2023.

In the second case, a 68-year-old man with long-standing generalized MG previously managed the condition with several treatments which included steroids, pyridostigmine, azathioprine, and immunoglobulin. Eculizumab (Soliris; Alexion) was introduced later because of persistent symptoms but the treatment resulted in AEs. When switched to ravulizumab in December 2022, alongside treatment of azathioprine 50 mg, findings showed stable clinical improvement in the patient. Then, at follow-up of 11 months, the patient achieved an MG-ADL score of 0 and resumed their normal activities.

In the third case, a 32-year-old woman with Hashimoto thyroiditis and MG diagnosed at age 15 reported an average of 2 exacerbations each year despite being on treatment with steroids, immunosuppressant, and plasmapheresis. In August 2023, the patient switched to ravulizumab infusions every 8 weeks with immunoglobulins as needed because of scheduling difficulties. This change with treatment led to the patient to experience symptomatic improvement, no exacerbations at all, and achieved a stable MG-ADL score of 6.

In April 2022, the FDA approved ravulizumab as the first approved long-acting C5 complement inhibitor for this patient population.² The approval was based on data from the phase 3 CHAMPION MG trial (NCT03920293), in which treatment with ravulizumab resulted in rapid and sustained improvement of symptoms in patients with generalized MG for up to 26 weeks. At the end of the treatment period, investigators observed statistically significant improvements on the primary end point of MG-ADL total score compared with placebo (–3.1 vs –1.4; P <.001).²

Published in the New England Journal of Medicine Evidence, change in Quantitative Myasthenia Gravis (QMG) total scores, a secondary end point, showed statistically significant improvements following ravulizumab treatment compared with placebo (P <.001). The least squares estimate of the mean QMG change was –2.8 (95% CI, –3.7 to –1.9) in the ravulizumab group and –0.8 (95% CI, –1.7 to 0.1) in the placebo group (P <.001). QMG total scores improved by 5 points or more in a significantly greater proportion of ravulizumab-treated patients than of those receiving placebo (30.0% vs 11.3%; P = .005).³

In the trial, the proportion of patients who experienced AEs or AEs related to the study drug were similar between the treatment groups. There were no notable differences in the types of AEs, with the most frequent event being headache, experienced by 16 patients (19%) in the ravulizumab group and 23 (26%) in the placebo group. Serious AEs were reported in 23% and 16% in the ravulizumab and placebo groups, respectively, the most frequent of which were related to worsening of MG and COVID-19. Two serious AEs (dysphasia and tendonitis) in 2 ravulizumab-treated patients and 4 (cellulitis [2 cases], herpes zoster infection, and infusion-related reaction) serious AEs occurred in the placebo group and were considered treatment-related.