Rituximab for the Treatment of Neuromyelitis Optica Spectrum Disorder

Abstract


 Four systematic reviews, 1 randomized controlled trial (RCT), 1 economic evaluation, and 2 evidence-based guidelines were identified.
 Four systematic reviews (2 that included moderate- to high-quality evidence and 2 that did not report the quality of the evidence) and 1 RCT (that provided high-quality evidence) reported on the clinical effectiveness of rituximab (RTX) for the treatment of neuromyelitis optica spectrum disorder (NMOSD). Overall, RTX treatment appeared to reduce the relapse rate and disability level compared with pre-treatment or placebo. In terms of reduction in relapse rate and disability, RTX was either better or not different from azathioprine (AZA). For relapse rates, disability levels, and incidence of adverse events, network meta-analyses showed that no treatment was favoured for comparisons between RTX, mycophenolate mofetil (MMF), and cyclophosphamide (CYP).
 One economic evaluation (of moderate quality) showed that, for patients with NMOSD, in the context of the Thai health care system, RTX biosimilar with CD27+ memory B cell monitoring regimen had the highest probability (48%) of being cost-effective, followed by AZA (30%), MMF (13%), RTX with CD27+ memory B cell monitoring regimen (9%), RTX biosimilar (0%), and RTX (0%) at a willingness-to-pay threshold of 160,000 Thai bhat (equivalent to US$5,289 in 2019 values) per quality-adjusted life-year gained.
 The 2 guidelines recommended immunosuppressants (RTX, AZA, and MMF) for prevention of NMOSD attacks. In addition, 1 guideline mentioned that tocilizumab, eculizumab, inebilizumab, and satralizumab can be used in NMOSD leave it up to patients who have no response to other immunosuppressants. The quality of the evidence that informed the guidelines and the strength of the recommendations were not reported.
 Findings need to be interpreted with caution given the limited quantity of evidence on comparative efficacy and safety between various immunosuppressants, that many of the included primary studies were retrospective studies, the heterogeneity among the studies included in the systematic reviews, and the lack of clarity with respect to the strength of the recommendations.

Tocilizumab for Neuromyelitis Optica Spectrum Disorder

“…The critical appraisal of the included clinical practice guideline 24 was performed in a previous CADTH report on rituximab for NMOSD. 29 More details about the quality of the guideline can be found in the reports. Briefly, the guideline had clear descriptions of scope, population, target users, guideline developers, and was externally peer-reviewed.…”

“…The clinical practice guidelines 24 from Latin America presents statements on various treatments for patients with NMOSD, described in detail in a previous CADTH report. 29 For long-term relapse prevention, the guideline recommends the early start of immunosuppressant treatments to reduce disease activity and prevent NMOSD attacks.…”

Adverse Events in NMOSD Therapy

“…Nikoo et al compared rituximab with azathioprine [32] in terms of efficacy, and the RIN-1 study by Tahara et al compared rituximab with a placebo [33]. Only recently, the Canadian Agency for Drugs and Technologies in Health (CADTH) published a Health Technology Report on rituximab in NMOSD, which covered safety as well [34].…”

A meta-analysis on efficacy and safety of rituximab for neuromyelitis optica spectrum disorders

“…Cabre et al 2018 [2] Prospective 32 30/2 39.9 (12.1) 20 NC 2 yr Dastjerdi et al 2018 [5] Prospective 56 46/10 36.86 30 87.60 ± 59.65 mo 6/12 mo Fernández-Megía et al 2015 [6] Retrospective 6 6/0 46 (38-58) 3 NC NC Jacob et al 2008 [7] Retrospective 25 22/3 38 (7-65) 14 4.5 (0.8-17) yr 19 (6-40) mo Kim et al 2015 [3] Retrospective 100 92/8 43 (11) 94 11 (5) yr 67 (9-108) mo Nikoo et al 2017 [8] RCT 33 29/4 35.33 (8.98) 13 6.23 (4.29) yr 12 mo Shaygannejad et al 2019 [9] Prospective 44 35/9 37.2 ± 10.4 14 6.3 ± 4.1 yr 31.6 ± 7.3 mo Zephir et al 2015 [10] Retrospective 32 27/5 45 ± 12.1 28 6.5 (1-410) mo 28.7 ± 21 mo Zhang et al 2017 [11] Retrospective 31 23/8 42.2 ± 16.9 25 4.05 ± 2.11 yr >2 yr Annovazzi et al 2016 [12] Retrospective 73 64/9 46.5 ± 12.5 53 6 ± 7.2 yr 35.6 ± 27 Pellkofer et al 2011 [13] Prospective 9 8/1 36.1 (11.5) 9 11 (7.7) yr 29.6 (14.5) mo Lindsey et al 2012 [14] Retrospective 8 7/1 37.6 (14.4) 4 65.1 (53.7) mo 39.9 (40.7) mo Ip et al 2013 [15] Retrospective 7 6/1 52 (22-62) 4 57 (40-272) mo 24 (1-42) mo Jeong et al 2016 [16] Retrospective 55 50/5 42 (15-68) 52 41.7 (2.1-231.5) mo 64.7 (6.2-99.8) mo Collongues et al 2016 [17] Retrospective 21 19/2 37.8 (15.5) 19 46.9 (51.2) mo 31 (18) mo Cohen et al 2017 [18] Prospective [20] Retrospective 23 21/2 37.1 ± 14.6 15 114 (13-266) mo 32.5 (7-63) mo Casallas-Vanegas et al 2020 [21] Retrospective 66 54/12 36.2 ± 12.01 44 5.85 ± 4.03 yr NC Correa Diaz et al 2019 [22] Retrospective 21 18/2 36.7 (13.3) NC NC 24.8 (6-47) mo Flores et al 2012 [23] NC 13 12/1 33.3 ± 13.8 NC NC 24 mo Kim et al 2009 [24] NC 27 24/3 33.5 ± 11.6 NC 5.6 ± 3.6 yr NC Kim et al 2013 [25] Retrospective 30 27/3 38 (23-58) NC 61 (49-82) mo NC Lin et al 2018 [26] RCT 14 NC 32.9 ± 13.6 NC 20.5 ± 6.8 mo NC Wu and Niu 2019 [27] Retrospective 15 13/2 31.8 ± 13.2 NC 1-144 mo NC Xiao et al 2020 [28] Retrospective 36 NC NC NC NC 19.83 ± 7.74 mo Bai 2016 [29] RCT 9 9 38.28 NC NC 7-40 mo Li 2019 [30] Retrospective 29 27/2 38.3 ± 13.9 27 NC 3.1/2.1 yr Liu 2017 [31] RCT 1...…”