May 31, 2019 Conference
Dr. Christine Kohn, University of Connecticut School of Medicine
Dr. William L Baker, University of Connecticut School of Pharmacy/Hartford Hospital Evidence-based Medicine
Dr. David M Waitzman, University of Connecticut Ophthalmology Department
Purpose: Neuromyelitis optica (NMO) is a rare autoimmune disorder that follows a relapsing/remitting course and often leaves patients severely disabled, despite aggressive treatment with traditional immunosuppressive medication. While off-label monoclonal antibody therapy has shown efficacy in treating NMO, no large randomized control trials (RCTs) exist. In lieu of such trials, we performed a systematic review and meta-analysis to assess the efficacy and safety of rituximab, eculizumab and tocilizumab in NMO patients.
Methods: We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase from January 1, 2006 through November 15, 2018 for prospective studies using rituximab, eculizumab or tocilizumab in NMO patients and reporting annual relapse rate (ARR) and Extended Disability Status Scale Score (EDSS) before and after monoclonal therapy. Endpoints were pooled using traditional random effects meta-analysis methods, producing mean differences and 95% confidence intervals (CI).
Results: Fifteen studies involving 324 patients were included in the systematic review and meta-analysis. Monoclonal therapy resulted in a statistically significant mean reduction in ARR of 1.77 (95% CI, 1.37 to 2.17) (Figure 1) and a statistically significant mean reduction in EDSS of 1.14 (95% CI, 0.87 to 1.41) (Figure 2). Severe adverse effects were reported in 7% (23/324) of patients. Specifically, 12 patients (3.7%) had a reactivation of or primary infection, 5 patients (1.5%) had persistent leukopenia, 3 patients (0.9%) experienced an infusion-related reaction/allergic response, 1 patient (0.3%) developed cancer, 1 patient (0.3%) developed atrial fibrillation and 1 patient (0.3%) died.
Conclusions: This systematic review and meta-analysis provides evidence that monoclonal antibodies, specifically rituximab, eculizumab and tocilizumab, have a reasonable efficacy and safety profile in the treatment of NMO patients. Treatment with monoclonal antibodies was shown to reduce the frequency of NMO relapses and improve neurological disability in affected individuals. However, large RCTs are needed to definitively demonstrate their effectiveness and safety.