Different Targets of Monoclonal Antibodies in Neuromyelitis Optica Spectrum Disorders: A Meta-Analysis Evidenced From Randomized Controlled Trials

Abstract

Background: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune inflammatory disorder of the central nervous system, often leads to vision loss or paralysis. This meta-analysis focused on the assessment of the monoclonal antibody therapy in NMOSD and compared different targets of monoclonal antibodies with each other in terms of efficacy and safety outcomes.Method: We searched through the databases of MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov for randomized controlled trials (RCTs) evaluating monoclonal antibody therapy in NMOSD up to April 2020.Results: We identified seven randomized controlled trials (RCTs), including 775 patients (monoclonal antibody group, n = 485 and placebo group, n = 290). Monoclonal antibody therapy decreased relapse risk (RR 0.33, 95% CI 0.21–0.52, P < 0.00001), annualized relapse rate (ARR) (mean −0.28, 95% CI −0.35−0.20, P < 0.00001), expanded disability status scale score (EDSS) (mean −0.19, 95% CI −0.32−0.07, P = 0.002) and serious adverse events (RR 0.78, 95% CI 0.61–1.00, P = 0.05). However, we did not observe any significant difference in terms of adverse events or mortality. Further, the subgroup analysis demonstrated that the anti-complement protein C5 monoclonal antibody (eculizumab) might have a lower relapse risk (RR 0.07, 95% CI 0.02–0.23, P < 0.0001) in the AQP4 seropositive patients, and anti-interleukin-6 receptor monoclonal antibodies (satralizumab and tocilizumab) showed decreased EDSS score (mean −0.17, 95% CI −0.31−0.02, P = 0.02) more effectively than other monoclonal antibodies.Conclusions: Monoclonal antibodies were effective and safe in NMOSD. Different targets of monoclonal antibodies might have their own advantages.

Safety and efficacy of interleukin-6-receptor inhibitors in the treatment of neuromyelitis optica spectrum disorders: a meta-analysis

“…Though there is difference in the frequency but, most of the common side effects are similar. The frequency of most common adverse events like Upper respiratory tract infections, Urinary Tract Infections, hypercholesterolemia, and serious adverse events are similar to studies by Xie et al and Xue et al [ 28 , 29 ] Though, cardiovascular disease is the main safety of concern in Anti-Interleukin-6 receptor inhibitors like Satralizumab and Tocilizumab as a result of an increase in cholesterol levels; recent trials [ 20 ] have shown no increase in the risk of cardiovascular disease [ 30 ]. No mortality was observed in two trials of Satralizumab in comparison to two treatment related deaths in Tocilizumab used studies.…”

“…Sub-group analysis of this study found a significant decrease in on-trail relapse risk and EDSS at follow-up (analysis of two trials of Satralizumab) but non-significant difference in mean ARR among the treatment groups and placebo group. IL-6 inhibitors were also found to be superior to other monoclonal antibodies in reducing EDSS [ 28 ]. A meta-analysis describing the safety and efficacy of Tocilizumab has similar therapeutic outcomes as compared to our analysis considering results in a change in mean ARR and EDSS score following treatment as only more studies of Tocilizumab treatment were added in our analysis [ 29 ].…”

Adverse events of rituximab in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis

“…Aligned with RTX, these medications were developed based on the pathophysiology of NMOSD, three of which (eculizumab, inebilizumab, and satralizumab) have been approved by the FDA to treat NMOSD. The pooled studies 47–49 found that there were no significant AE or SAE differences among these monoclonal antibodies (including RTX), no AE increased when comparing with placebo or AZA, and few deaths occurred. In other major immune-related diseases, most AEs of RTX were mild or moderate, 50–52 so that they could be solved by symptomatic treatments such as reducing the drug infusion rates, providing minor supportive treatments (e.g.…”

Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases

“…Moreover, a significant correlation was found between the proportion of relapse-free patients and tocilizumab treatment ( 51 ). Another meta-analysis involving 775 patients from seven randomized controlled trials found that patients treated with tocilizumab or satralizumab exhibited significantly lower EDSS scores compared with patients treated with other monoclonal antibodies ( 52 ). Meanwhile, in a meta-analysis comprising a total of 202 patients with NMOSD from nine studies, Kharel et al.…”