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Suitable Dosage of Rituximab for NMOSD Associated With Lower Risk of Adverse Events

Disease Spotlight | <b>Disease Spotlight: NMOSD</b>

A meta-analysis suggests that 100mg/w rituximab for 3 consecutive weeks may be the appropriate dosage for patients of NMOSD, demonstrated by a low risk of adverse events.

In a systematic review and meta-analysis, rituximab (Rituxan; Genentech), a drug to prevent relapses in neuromyelitis optica spectrum disease (NMOSD), was found to be a safe treatment, particularly at a dosage of 100mg per week for 3 consecutive weeks. This meta-analysis provided insight into the choice dosage of immunosuppressive therapy for patients with NMOSD to help clinicians understand rituximab to make better clinical application decisions.1

Rituximab showed a significant reduction in annual recurrence rate (ARR) (mean deviation [MD]= -1.79, 95% CI: –3.18 to –0.39, P = .01) and expanded disability status scale (EDSS) (MD= –1.35, 95% CI: –1.5 to –1.19, P <.00001) at 100 mg intravenous infusion per week for 3 consecutive weeks, meanwhile increasing the number of patients free of relapse (rate ratio [RR],24.61; 95% CI,5.11-118.55; P <.0001) and being relatively safe and without serious adverse events (SAE).

Lead coauthor Kenhui Wei, Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China, and colleagues wrote, "from the perspective of ARR, patients treated with 100mg/w for 3 weeks of rituximab had significantly lower levels of relapse. There was also a significant difference in the number of patients free of relapse before and after rituximab treatment. For the EDSS scores, 100mg/w for 3 weeks was effective in preventing or delaying the progression of disability.”1

The reviewers searched relevant studies up to March 2022 on PubMed, Embase, the Cochrane Library, and Clinicaltrials.gov on the evaluation of rituximab for NMOSD, with data analyzed using Review Manager 5.3 and Stata 14 software. Random effects models were used for the analysis of the means and standard deviations as well as the risk ratio.

A total of 576 patients across 17 studies were analyzed for the review. The change in ARR, EDSS, and the number of patients free of relapse between pre-treatment and post-treatment of rituximab was the primary end point of efficacy. As for safety, the reviewers summarized and compared the adverse events (AE) and serious AEs from the selected studies.

Wei et al noted that the studies revealed, “1000 mg twice with two weeks apart is effective in reducing ARR and EDSS, but AEs, SAEs and high costs make it less likely to be selected. Low doses of rituximab at 100mg/w for 3 weeks were significantly effective in reducing ARR and disability rates, with a lower financial burden on patients or the public health system, and a lower risk of adverse events than other doses.”1

Other additional findings showed that patients treated with rituximab 375mg/m2 weekly over 4 weeks and 1000 mg given twice in two weeks apart was associated with a significantly higher risk of SAEs and AEs. Overall, 3 deaths occurred in this dosed group, with aspiration pneumonia, disease complication, and myelitis that reached the medulla oblongata as the 3 causes.

Limitations of this analysis included some bias found in most of the cohort studies that reported on the low prevalence, high recurrence rate, and high or even fatal disability of NMOSD. In addition, there was no statistical analysis conducted on prior immunosuppressive therapy and thus, that review was not registered before data collection. The role of maintenance therapy was not regarded even though a meta-regression analysis has shown that the amount of rituximab doses did not affect the ARR and EDSS scores in patients with NMOSD.2

“More large-sample and long-term monitoring RCT studies of rituximab are expected in the future, with more efforts to determine the optimal dose and duration of rituximab, assess risk factors at the patient level, and identify the population at highest risk for AEs. We are looking forward to more studies related to rituximab so that it may have a promising future in the therapy strategy of NMOSD,” Wei et al noted.1

REFERENCES
1. Wei K, Nie Q, Zhu Y, Lu H, Xue Q, Chen G. Different doses of Rituximab for the therapy of Neuromyelitis optica spectrum disorder: A systematic review and meta-analysis. Mult Scler Relat Disord. 2022;68:104127. doi:10.1016/j.msard.2022.104127
2. Damato V, Evoli A, Iorio R. Efficacy and Safety of Rituximab Therapy in Neuromyelitis Optica Spectrum Disorders: A Systematic Review and Meta-analysis. JAMA Neurol. 2016;73(11):1342-1348. doi:10.1001/jamaneurol.2016.1637