Eculizumab, satralizumab, or inebilizumab for NMOSD?

An indirect comparison analysis suggests that eculizumab is more effective than satralizumab and inebilizumab at lowering the risk of relapse in adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for aquaporin-4 protein autoantibodies (AQP4-IgG+). Not only was eculizumab superior to the other 2 agents with regard to time to first relapse, but superiority was observed both as a monotherapy and in combination with immunosuppressive treatments (ISTs), such as mycophenolate, azathioprine, or glucocorticoids [1,2].

Prof. Dean Wingerchuk (Mayo Clinic Phoenix/Scottsdale, AZ, USA) explained that given the absence of any head-to-head studies, his team conducted an indirect comparison based on published studies up to September 2020 from controlled trials testing eculizumab, satralizumab, and inebilizumab individually. He also acknowledged that there are limitations to this type of analysis, and pointed out that all 3 agents are very effective in treating AQP4+ NMOSD.

The meta-analysis incorporated data from 29 studies from 4 placebo-controlled clinical trials — collectively including 551 patients: N-MOmentum phase 2/3 clinical trial (NCT02200770), PREVENT phase 3 trial (NCT01892345), and SAkuraStar (NCT02073279) and SAkuraSky (NCT02028884) phase 3 trials. Time-to-first relapse was the only outcome measure reported across all trials and was therefore used in the comparison efficacy analysis.

The researchers conducted 3 separate analyses: 1 comparing the 3 therapies alone, another comparing eculizumab with satralizumab, given alone or in combination with ISTs, and the 3^rd comparing the eculizumab-IST combination with the satralizumab-IST combination. The results showed that eculizumab alone led to a significantly reduced risk of first relapse, compared with both satralizumab (by 90%) and inebilizumab (by 89%). When given alone or in combination with ISTs, eculizumab was also associated with a 76% reduced risk of first relapse relative to satralizumab. Furthermore, patients treated with combination eculizumab-IST therapy were 59% less likely to experience the first relapse, compared with those receiving combination satralizumab-IST therapy, but this difference did not reach statistical significance (see Table).

Table: Hazard ratios for time to first relapse [1]
IST, immunosuppressant therapy

Prof. Wingerchuck concluded: “Based on current evidence, monotherapy and mono-combination therapy with eculizumab appear to be more efficacious at preventing relapses than satralizumab or inebilizumab for the treatment of adults with AQP4+ NMOSD. These findings suggest that C5 complement inhibition with treatments such as eculizumab prevent relapses more effectively than other mechanisms involving IL-6 receptor or CD19 inhibition among adults with AQP4+ NMOSD.” However, multiple factors need to be considered in the differential treatment decision process [3].

1. Wingerchuck DM, et al. Indirect comparison analysis of FDA-approved treatment options for adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder. OP118, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Wingerchuck DM, et al. Neurol Ther 2021;Nov 13. DOI:10.1007/s40120-021-00295-8
3. Hartung HP. Ann Neurol. 2021 Jun;89(6):1084–1087.

 

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Posted on 9 December, 202110 December, 2021