Efficacy of monoclonal antibodies in neuromyelitis optica: An updated systematic review with meta‐analysis

Abstract

Objective: This is a critical review of studies aiming to assess the safety and efficacy of monoclonal antibodies as compared with the classical regimen in patients with neuromyelitis optica spectrum disorder.Methods: Various electronic databases were searched for original articles reporting results from the use of monoclonal antibodies in neuromyelitis optica spectrum disorder. The Expanded Disability Status Scale and annualized relapse rate score before and after treatment were the primary effect measures. The pooled standardized mean difference with 95% CI was calculated using the random effects model. The heterogeneity of the included studies was calculated using Cochran's Q test and I 2 statistics. Results:Of 36 included studies, meta-analysis was carried out from 27 studies. The pooled analysis of 1010 patients showed a mean reduction in the mean annualized relapse rate ratio after tocilizumab therapy −2.45 (95% CI −3.13 to −1.77) to be higher compared with rituximab −1.49 (95% CI −1.81 to −1.17). Likewise, the mean reduction in the Expanded Disability Status Scale after tocilizumab was higher −1.10 (95% CI −1.75 to −0.44) compared with rituximab −0.80 (95% CI −1.11 to −0.48). Conclusion:Tocilizumab has a greater effect than rituximab in terms of the reduction of the annualized relapse rate and Expanded Disability Status Scale in neuromyelitis optica spectrum disorder patients. The greater efficacy of tocilizumab could result from its multiple dynamic pharmacodynamics (i.e. its effect on interleukin-6-dependent inflammatory processes, involving CD20-negative plasmablasts, pathogenic T cells and regulatory T cells) and to some degree due to heterogeneity in our study. Satralizumab (monotherapy or add-on), eculizumab and inebilizumab (monotherapy) are effective in aquaporin-4-positive cases with good safety profiles. Ublituximab, bortezomib, bevacizumab and C1-esterase inhibitors are both effective and safe add-on drugs.

Tocilizumab for Neuromyelitis Optica Spectrum Disorder

“…25 Three systematic reviews 18,20,21 included the same RCT (TANGO trial), which compared TCZ and AZA. 26 Two systematic reviews 20,21 were published in 2021, 1 systematic review 19 was published in 2022 and the fourth systematic review 18 was published in 2023 with the search up to July 21, 2022.…”

“…The fourth systematic review 21 did not report the proportion of females. The proportion of patients with AQP4-positive serotype ranged from 14% to 100% across primary studies in 1 systematic review, 19 40% to 100% in the second review, 20 and was reported as 85.8% in patients with TCZ treatment in the third systematic review and 81.3% for the fourth systematic review. 18 One review 20 noted that AZA and mycophenolate mofetil were the most common add-on drugs for TCZ, while the remaining systematic reviews 18,19,21 did not report the add-on drugs.…”

“…Four systematic reviews, [18][19][20][21] 2 non-randomized studies, 22,23 and 1 evidence-based guideline 24 were included. Three systematic reviews [19][20][21] had broader inclusion criteria on interventions; only the subset of studies reporting on TCZ and its comparison were relevant to the current report. We only described the characteristics and results of this subset in this report.…”

“…All 4 systematic reviews [18][19][20][21] involved patients with NMOSD, and the number of included patients ranged from 59 to 1,078. The age of patients ranged from 12 years to 68 years with mean age ranging from 29 years to 50 years in primary studies included in 1 systematic review; 20 mean ages were 42 years (TCZ studies) and 37 years (AZA studies) in the second systematic review; 18 the mean age ranged from 29 to 50 in the primary studies included in the third systematic review; 19 and age was not reported in the fourth systematic review. 21 The study populations were predominantly female in 3 systematic reviews 18-20, with the proportion of females ranging from 86% to 92%.…”

“…Two systematic reviews 18,21 compared the effectiveness and safety of TCZ and AZA, and the remaining 2 systematic reviews 19,20 compared the before-and-after changes for TCZ without a comparator group. Two systematic reviews 18,19 did not report the dosage and route of administration of TCZ.…”