Immunosuppression in Neuromyelitis Optica Spectrum Disorder: A Trial Sequential Analysis and Updated Meta-Analysis
Artur Menegaz de Almeida1, Juan Diego Martinez-Lemus2, Maria Eduarda Cavalcanti3, Francisco Cezar Aquino de Moraes4, Fernando Westphal Filho5, Paulo Roberto Moss Lopes5, Ítalo Barros Andrade6, Clara Rocha Dantas7, Mariana Rachas Reis8, Maria I Reyes-Mantilla9
1Federal University of Mato Grosso, 2Movement Disorders and Neurodegenerative Diseases Division, Department of Neurology, McGovern Medical School at UTHealth Houston, 3University of Pernambuco, 4Federal University of Pará, 5Federal University of Amazonas, 6Faculdade Santo Agostinho, 7Buenos Aires University, 8Santa Casa University of Medical Sciences, 9Neuroimmunology and Neurological Infectious Disorders Division, Johns Hopkins University School of Medicine
Objective:
To compare the safety and efficacy of RTX, AZA, and MMF through an updated meta-analysis and assess the reliability of these findings using trial sequential analysis (TSA).
Background:
Neuromyelitis Optica Spectrum Disorder is an autoimmune disease affecting the spinal cord, optic nerves, and brainstem; first-line therapies include Rituximab, Azathioprine, and Mycophenolate Mofetil, but their non-inferiority remains inconclusive.
Design/Methods:
MEDLINE, SCOPUS, Web of Science, and Cochrane were systematically for observational studies, as well as single-arm and double-arm randomized controlled trials involving NMOSD patients treated with RTX, AZA, and/or MMF. We used RStudio version 4.3.2 and TSA software for statistics.
Results:
37 studies and 2,047 patients were included in the meta-analysis: 1,336 (65.26%) on RTX, 417 (20.37%) on AZA, and 294 (14.36%) on MMF. ARR mean differences improved after treatment with RTX (MD: -1.33, p<0.001), AZA (MD: -0.90, p=0.004), and MMF (MD: -1.12, p<0.001). EDSS improved only with RTX (MD: -0.89, p<0.01). Comparisons of RTX with AZA and MMF showed no significant differences in ARR or EDSS (RTX vs AZA: ARR p=0.05, EDSS p=0.372; RTX vs MMF: ARR p=0.06, EDSS p=0.576). RTX had lower relapse risk (RTX vs. AZA HR: 1.57, p=0.05; RTX vs. MMF HR: 1.93, p<0.001), fewer adverse events (2.83% vs 10.33%, RR: 0.42, p=0.027), lower rates of elevated transaminases (RTX vs AZA: 0% vs 19.7%, p<0.001; RTX vs MMF: 0% vs 17.03%, p=0.015), and less leukopenia (RTX vs AZA: 0% vs 17.46%, p=0.041), but a higher risk of infections (RTX vs MMF: 9.34% vs 2.32%, p=0.033). TSA confirmed findings for ARR and adverse events but was inconclusive for EDSS.
Conclusions:
AZA and MMF reduce ARR and EDSS for NMOSD as effectively as RTX but do not reduce the time to relapse. RTX has fewer adverse events but a higher infection risk. Non-specific immunomodulators can be valuable in settings where RTX is unavailable.
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