Low-Dose Rituximab Effective Against MuSK-Positive MG in New Analysis

Notes on myasthenia gravis

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For patients who have muscle-specific kinase–positive myasthenia gravis (MuSK-MG), low-dose rituximab was proved effective, according to a new analysis published in Neuroscience Letters that evaluated disease severity before and after treatment in the Neurology Department of First Hospital, Shanxi Medical University, from April 2021 to April 2023.¹

Following research that showed rituximab was an effective treatment for MuSK-MG,^2-5 the investigators implemented the treatment at their hospital. Compared with high-dose rituximab, additional benefits of low-dose rituximab include lower risks of myocardial infarction, spondylodiscitis, neutropenia, and diverticulitis.

This retrospective analysis covered 9 patients (8 female patients) with MuSK-positive disease of the 204 patients who had MG and were admitted. Their age range was 20 to 73 years; disease duration, 3 to 56 months; and follow-up, 3 to 21 months. Most presented with ptosis and/or diplopia. They received 1 to 4 cycles of low-dose rituximab, which entailed an induction regimen of 100 mg on day 1 and 200 mg each on days 2 and 3 and subsequent 500-mg treatments very 6 months or yearly. Baseline measures were taken on day 1. Effectiveness was evaluated via Myasthenia Gravis Foundation of America (MGFA) classification; Myasthenia Gravis Foundation of America-Post Intervention Status (MGFA-PIS); MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) scores; and steroid dosages at the end of the follow-up period.

Results show improvements from MGFA classifications of IIb (2 patients), IIIb (4 patients), and V (3 patients) to IIa (2 patients), IIb (3 patients), and asymptomatic (4 patients), indicating pharmacologic remission, minimal disease manifestation, and improved statuses via MGFA-PIS. In addition, the mean (SD) prednisolone dose dropped to 18.33 mg at the final follow-up vs 50 mg at baseline (P = .001). Two patients ended with a 10-mg or less dose of prednisolone.

There were significantly improved scores on the MG-ADL, QMG, and MG-QOL15r scales. At baseline, these medians were 10 (range, 3-20), on a scale of 0 to 24; 11 (range, 5-27), indicating moderate disease severity; and 32 (range, 14-55), indicating significant impact on QOL, respectively. At the last study visit, the scores had dropped to less than 3 (Z = −2.675; P < .01), 5 or lower (Z = −2.366; P < .05), and 6 or less (Z = −2.547; P < .01).

No serious adverse effects or allergic reactions were seen, “indicating that low-dose rituximab was well tolerated by all patients,” the authors indicated.

They added that the typical induction regimen of rituximab treatment in patients with MuSK-positive MG is 4 weekly doses of 375 mg—if the patient is on a high-dose regimen—compared with the 100-mg dose they evaluated and that every patient in their analysis was able to achieve level 2 or higher on the Myasthenia Gravis Status and Treatment Intensity. Previous research demonstrates achieving this level indicates clinical improvement.⁶

An additional strength of their findings, they noted, is that their low-dose rituximab regimen was able to achieve comparable results in daily steroid use vs a high-dose regimen.

Still, they recommend future research “to fully ascertain the long-term effectiveness and safety of this therapy. Specifically, implementation of a larger-scale, prospective, double blind, randomized, and controlled trial.”

References

1. Promising efficacy of low-dose rituximab in muscle specific kinase antibody positive myasthenia gravis. Neurosci Lett. Published online November 19, 2023. doi:10.1016/j.neulet.2023.137561
2. Iorio R, Damato V, Alboini PE, Evoli A. Efficacy and safety of rituximab for myasthenia gravis: a systematic review and meta-analysis. J Neurol. 2015;262(5):1115-1119. doi:10.1007/s00415-014-7532-3
3. Zhou Y, Yan C, Gu X, at al. Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody. Muscle Nerve. 2021;63(6):824-830. doi:10.1002/mus.27233
4. Díaz-Manera J, Martínez-Hernández E, Querol L, et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology. 2012;78(3):189-193. doi:10.1212/WNL.0b013e3182407982
5. Hehir MK, Hobson-Webb LD, Michael Benatar et al., Rituximab as treatment for anti-MuSK myasthenia gravis. Neurology. 2017;89(10):1069-1077. doi:10.1212/WNL.0000000000004341
6. Vu TH, Suresh N, Myasthenia gravis. Practical Neurology. Published July/August 2021. Accessed December 29, 2023. https://practicalneurology.com/articles/2021-july-aug/myasthenia-gravis#:~:text=Clinical%20improvement%20was%20defined%20as,dosages%20of%20other%20immunosuppressant%20therapies