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Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis
  1. Gregorio Spagni1,2,
  2. Bo Sun3,
  3. Gabriele Monte1,4,
  4. Elia Sechi5,
  5. Raffaele Iorio2,
  6. Amelia Evoli1,2,
  7. Valentina Damato1,6
  1. 1 Neuroscience Department, Universita Cattolica del Sacro Cuore Facolta di Medicina e Chirurgia, Roma, Italy
  2. 2 Neurology Institute, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy, Roma, Italy
  3. 3 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  4. 4 Neuroscience, Ospedale Pediatrico Bambino Gesù, Roma, Italy
  5. 5 Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
  6. 6 Department of Neurosciences, Drugs and Child Health, University of Florence, Firenze, Italy
  1. Correspondence to Dr Valentina Damato, Neuroscience, Catholic University of the Sacred Heart Faculty of Medicine and Surgery, Roma, Italy; valentina.damato{at}


Background Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD.

Methods We searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and, reporting data on RTX efficacy in patients with MOGAD. The main outcome measures were annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score mean differences (MDs) after RTX. The meta-analysis was performed with a random effects model. Covariates associated with the outcome measures were analysed with a linear meta-regression.

Results The systematic review included 315 patients (138 women, mean onset age 26.8 years) from 32 studies. Nineteen studies (282 patients) were included in the meta-analysis. After RTX, a significant decrease of ARR was found (MD: −0.92, 95% CI –1.24 to –0.60, p<0.001), markedly different from the AQP4-IgG+NMOSD (MD: −1.73 vs MOGAD −0.92, subgroup difference testing: Q=9.09, p=0.002). However, when controlling for the mean ARR pre-RTX, this difference was not significant. After RTX, the EDSS score decreased significantly (MD: −0.84, 95% CI −1.41 to –0.26, p=0.004). The frequency of RTX-related adverse events was 18.8% (36/192) and overall RTX-related mortality 0.5% (1/192).

Conclusions RTX showed effective in MOGAD, although to a lesser extent than in AQP4-IgG+NMOSD, while the safety profile warrants some caution in its prescription. Randomised-controlled trials are needed to confirm these findings and provide robust evidence to improve treatment strategies in patients with MOGAD.

PROSPERO registration number CRD42020175439.


Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • GS and BS are joint first authors.

  • Twitter @damato_v

  • Contributors VD, GS contributed to study concept and design. VD, GS, GM contributed to acquisition of data. VD, GS, BS contributed to analysis and interpretation of data. VD, GS, BS contributed to drafting of the manuscript. VD, GS, BS, GM, ES, RI, AE contributed to critical revision of the manuscript for important intellectual content. VD, AE contributed to study supervision. VD is the guarantor.

  • Funding GS is supported by the Italian Ministry of Health (Rete delle Neuroscienze e della Neuroriabilitazione). BS is supported by the National Institute for Health Research (Award ID: CL 2021-13-002). VD is supported by the Myasthenia Gravis Rare Disease Network – MGNet (Grant number: PTE federal award n. 5U54NS115054-03, subaward n. 21-M73-INT). The funders had no role in study planning and conduction.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.