Rituximab shows superiority over azathioprine and mycophenolate mofetil as initial treatment for NMOSD

New data from a study published in the European Journal of Neurology add to the available evidence supporting rituximab in the treatment of neuromyelitis optica spectrum disorder (NMOSD), with retrospective study results suggesting that reduced-dose rituximab is superior to azathioprine and mycophenolate mofetil.1

Ultimately, the risk of NMOSD relapse was significantly reduced in patients treated with rituximab compared to those who were on azathioprine (RR, 4.40; 95% CI, 1.41-13.80; P = 0.011) or mycophenolate mofetil (RR, 5.20; 95% CI, 1.60-16.86; P = 0.006).

Comprised of over 300 patients with aquaporin-4 (APQ4) antibody positive NMOSD in China who were initially treated with azathioprine (n=167), mycophenolate mofetil (n=131), or rituximab ( n=55), the study was conducted by Chao Quan, MD, Department of Neurology and Huashan Rare Disease Center, Huashan Hospital and Shanghai Medical College, Fudan University; and National Center for Neurological Disorders, and colleagues from the Pan-Yangtze River Delta Alliance for Demyelinating Disease.

“Data regarding the efficacy and safety of preventive therapies currently widely available in [NMOSD] are needed,” wrote Quan et al. The group concluded that “We provide class III evidence that a reduced dose of [rituximab] is greater than [azathioprine] and [mycophenolate mofetil] as initial treatment to reduce the risk of relapse and is better tolerated than [azathioprine]in Chinese patients with NMOSD positive for the AQP4 antibody.

Notably, treatment discontinuations were also less likely for those in the rituximab group compared to the azathioprine group (HR, 2.22; 95% CI, 1.34-3.66; P = .002). Regarding safety, the rituximab group had a lower incidence of AEs (32.7%) than the azathioprine group (62.3%; P <.001>

The primary endpoint of the study was the occurrence of relapse after the start of immunotherapy, while the secondary endpoints were annual relapse rate (ARR), accumulation of disability, persistence medication and adverse events (AEs). The median duration of patient follow-up for the cohort of 353 patients was 30.3 months. Patients in the rituximab group were treated with 100 mg on day 1, followed by 500 mg on day 2, continuing at this dose every 6 months. Among those in the rituximab group, 76.4% were on concomitant corticosteroid therapy. Among those in the azathioprine and mycophenolate mofetil groups, these percentages were 96.4% and 95.4%, respectively.

These data add to an ever-growing base of findings suggesting the efficacy of rituximab in the treatment of NMOSD.2-5 Previously, systematic reviews have suggested that therapy with the agent reduces the frequency of NMOSD relapse rates and neurological disability in patients with NMOSD.2.5 This efficacy may be driven by the effect of treatment on germinal center activity, according to recent findings by Sarosh R. Irani, DPhil, FRCP, FEAN, Head, Oxford Autoimmune Neurology Group, University of Oxford and colleagues.6

“Our findings imply [germinal center] activity as a rituximab-sensitive driver of AQP4 antibody production. They may explain the clinical efficacy of rituximab in several autoantibody-mediated diseases and highlight the potential value of [germinal center] measures in autoimmune conditions,” wrote Irani et al, adding that therapy efficacy occurs “despite the lack of concomitant reduction in serum autoantibody levels.”

Irani et al observed clinical relapses associated with features of germinal center activity such as generation of aquaporin-4 (AQP4-IgG) antibody immunoglobulins or changes in AQP4-IgG subclasses (ratio odds [OR], 6.0; range, 3.3-10.8; P <.0001 additionally once rituximab was administered investigators reported fewer clinical relapses relapse rate to>P <.001 accompanied by significant reductions equivalent to changes in aqp4-igg>P = 0.004) and 430-fold changes in intranodal B cells (P 6

REFERENCES
1. Huang W, Wang L, Xia J, et al. Efficacy and safety of azathioprine, mycophenolate mofetil, and reduced dose rituximab in neuromyelitis optica spectrum disorder. Eur J Neurol. 2022;29(8):2343-2354. doi:10.1111/ene.15355
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
3. Uzunköprü C, Tütüncü M, Gündüz T, et al. The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: a real-world study from Turkey. Int J Clin Practical. 2021;75(7):e14158. doi:10.1111/ijcp.14158
4. Tahara M, Oeda T, Okada K, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): multicenter, randomized, double-blind, placebo-controlled trial. Neurol Lancet. 2020;19(4):298-306. doi:10.1016/S1474-4422(20)30066-1
5. Wang Y, Chang H, Zhang X, Yin L. Efficacy of rituximab in the treatment of neuromyelitis optica spectrum disorders: A systematic review and meta-analysis update. Mult Scler Relat Disord. 2021;50:102843. doi:10.1016/j.msard.2021.102843
6. Damato V, Theorell J, Al-Diwani A, et al. Rituximab suppresses aquaporin-4-specific germinal center activity in patients with neuromyelitis optica spectrum disorders. PNAS. 2022;119(24):e2121804119. doi:10.1073/pnas.2121804119

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