Appropriate rituximab dosing for NMOSD associated with lower 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 shown to be a safe treatment, particularly at a dose of 100 mg per week for 3 consecutive weeks. This meta-analysis provided insight into the choice of immunosuppressive therapy dosage 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 difference [MD]= -1.79, 95% CI: -3.18 to -0.39, P = 0.01) and Expanded Disability Status Scale (EDSS) (MD = -1.35, 95% CI: -1.5 to -1.19, P <.00001 at a rate of mg intravenous infusion per week for consecutive weeks while increasing the number patients without relapse ratio ci>P <.0001 and being relatively safe without serious adverse events>

Co-lead author 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 100 mg/wk for 3 weeks of rituximab had significantly lower levels of relapse. There was also a significant difference in the number of relapse-free patients before and after rituximab treatment. For EDSS scores, 100 mg/s for 3 weeks was effective in preventing or delaying disability progression. »1

Reviewers searched PubMed, Embase, the Cochrane Library and Clinicaltrials.gov for relevant studies up to March 2022 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 means and standard deviations as well as relative risk.

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

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

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

Limitations of this analysis included some biases found in most cohort studies that accounted for the low prevalence, high recurrence rate, and high disability, even fatality, of NMOSD. Additionally, no statistical analysis was performed on prior immunosuppressive therapy and therefore this review was not recorded prior to data collection. The role of maintenance treatment was not considered even though a meta-regression analysis showed that the amount of rituximab doses did not affect ARR and EDSS scores in patients with NMOSD.2

“Further large-sample, long-term surveillance RCT studies of rituximab are expected in the future, with more efforts to determine the optimal dose and duration of rituximab, assess patient-level risk factors and identify the population most at risk of IE. . We look forward to further studies related to rituximab so that it may have a promising future in the therapeutic strategy of NMOSD,” noted Wei et al.1

REFERENCES
1. Wei K, Nie Q, Zhu Y, Lu H, Xue Q, Chen G. Different doses of rituximab for the treatment of neuromyelitis optica spectrum disorder: 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 treatment in neuromyelitis optica spectrum disorders: systematic review and meta-analysis. JAMA Neurol. 2016;73(11):1342-1348. doi:10.1001/jamaneurol.2016.1637

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