The Alexion-sponsored study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) by Dean Wingerchuk, MD, of the Mayo Clinic in Scottsdale, Ariz.
Other experts in the field have highlighted limitations to the analysis and pointed out that all three agents are very effective in treating AQP4+ NMOSD, and many other considerations need to be taken into account as well as time to first relapse when selecting a therapy, leaving the door open for all three agents.
Dr. Wingerchuk explained that NMOSD is a rare severely disabling complement-mediated autoimmune neuroinflammatory disease of the central nervous system, characterized by devastating and unpredictable attacks (relapses) that can cause immediate and irreversible damage.
There are three recently approved monoclonal antibody treatment options in the United States for adults with AQP4+ NMOSD: eculizumab (Soliris, Alexion), inebilizumab (Uplizna, Horizon), and satralizumab (Enspryng, Genentech). A comparison of the relative treatment effects of these drugs would facilitate the treatment selection process, Dr. Wingerchuk said.
The objective of this study was to perform an indirect treatment comparison on the efficacy of these three FDA-approved treatment options for adults with AQP4+ NMOSD, in the absence of any head-to-head studies.
Using published data from randomized controlled trials, which were identified by a systematic literature review in September 2020, the researchers performed a Bayesian network meta-analysis to estimate the relative effects between eculizumab, inebilizumab, and satralizumab.
Network meta-analyses were performed for clinically relevant subpopulations based on three treatment networks: (1) patients who received monotherapy with one of the monoclonal antibodies or in combination with an immunosuppressant therapy; (2) patients who received monotherapy with the monoclonal antibody alone; and (3) patients who received a combination of both the monoclonal antibody and immunosuppressant therapy.
Time to first relapse was the primary efficacy outcome assessed. Relative treatment effects were expressed as hazard ratios and the probability that a treatment was the best at delaying time to first relapse was also evaluated.
In the systematic literature review, 29 publications from four unique clinical trials were identified and include in the network meta-analysis. These included publications from congress proceedings and peer-reviewed journals.
The four clinical trials were the N-MOmentum trial of inebilizumab versus placebo; the PREVENT trial of eculizumab with or without immunosuppressant therapy versus placebo with or without immunosuppressant therapy; the SAkuraSky trial of satralizumab plus immunosuppressant therapy versus placebo plus immunosuppressant therapy; and the SAkuraStar trial of satralizumab versus placebo.
Results showed that for the first analysis of mono or combination therapy, patients treated with eculizumab with or without immunosuppressant therapy were 76% less likely to experience a first relapse when compared with patients treated with satralizumab with or without immunosuppressant therapy.
In the monotherapy network, patients on eculizumab were 90% less likely to experience a first relapse when compared with patients treated with satralizumab, and patients on eculizumab were 89% less likely to experience a first relapse when compared with patients treated with inebilizumab.
In the third network analysis – a comparison of eculizumab plus immunosuppressant therapy with inebilizumab plus immunosuppressant therapy (Table 1) – the point estimate appeared to favor eculizumab but the confidence intervals were wide and not significant.
A subsequent analysis looked at the rank order of the best treatment option, with eculizumab coming out first in all three networks (Table 2).
Dr. Wingerchuk acknowledged that there were many limitations to this study, including that analyses for annualized relapse rate, disability, and quality of life were not included because of a lack of consistent outcome reporting by AQP4+ status in the randomized trials.
Safety outcomes were excluded because of a lack of standardized baseline risks and inconsistent reporting by AQP4+ status across trials.
Because this study focused on drugs approved in the United States in a rare disease area, there were a limited number of studies with intervention effects.
There were differences in follow-up durations across the different trials, with N-MOmentum having a follow-up of 197 days compared with 144 weeks for other trials.
“In the absence of head-to-head trials, this network meta-analysis provides important evidence on the relative efficacy of eculizumab versus satralizumab or inebilizumab for the treatment of patients with AQP4+ NMOSD, with significant differences in two out of the three treatment comparison scenarios observed,” Dr. Wingerchuk concluded.
“Based on current evidence, monotherapy and mono-combination therapy with eculizumab appear to more efficacious at preventing relapses than satralizumab or inebilizumab for the treatment of adults with AQP4+ NMOSD. These findings appear to suggest that C5 complement inhibition with treatments such as eculizumab appear to prevent relapses more effectively than other mechanisms involving IL-6 receptor or CD19 inhibition among adults with AQP4+ NMOSD,” he added.