Indirect Treatment Comparison of Ravulizumab Versus Approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-Positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD)
Stacey Clardy1, Sean Pittock2, Orhan Aktas3, Jin Nakahara4, Noriko Isobe5, Diego Centonze6, Sami Fam7, Adrian Kielhorn7, Jeffrey Yu7, Jeroen Jansen8, Ina Zhang8
1University of Utah, 2Mayo Clinic, 3Heinrich Heine University, 4Keio University, 5Kyushu University, 6Tor Vergata University, 7Alexion, AstraZeneca Rare Disease, 8PRECISIONheor
Objective:
To estimate relative treatment effects between ravulizumab and approved treatments (eculizumab, inebilizumab, and satralizumab) in adult patients with AQP4-IgG+ NMOSD.
Background:
NMOSD is an autoimmune disease that attacks the central nervous system. Considering several approved treatment options, a comparison of the relative treatment effects would facilitate selection of treatments for individual patients.
Design/Methods:
Based on the reported trial-specific results as identified from a systematic literature review, we estimated relative treatment effects between all competing interventions with network meta-analysis (NMA) techniques. The evidence base consisted of randomized controlled trials for all interventions except ravulizumab, which was evaluated in an external placebo-controlled trial. The endpoints of interest were time to first relapse (TTFR) and annualized relapse rate (ARR) with relative treatment effect measures obtained by the NMA expressed as hazard ratios (HR) and rate ratios (RR), respectively. Comparisons of the interventions were performed as monotherapy or in combination with immunosuppressants (ISTs). All analyses were performed in a Bayesian framework.
Results:
As monotherapy, ravulizumab was associated with a more than 90% reduction in experiencing a first relapse relative to satralizumab (HR [95% credible interval (Crl)], 0.08 [0.01-0.55]) and inebilizumab (0.09 [0.02-0.57]). TTFR was comparable between ravulizumab and eculizumab (0.86 [0.16-4.52]). Findings for ARR were consistent with TTFR; the rate of relapse with ravulizumab was 98% lower than with satralizumab (RR [95% Crl], 0.02 [0.00-0.42]) and inebilizumab (0.02 [0.00-0.38]) and was comparable to eculizumab. In combination with IST, ravulizumab showed an 85% reduction in first relapse relative to satralizumab (HR [95% Crl], 0.15 [0.03-0.78]).
Conclusions:
Ravulizumab is more efficacious at preventing relapse than satralizumab and inebilizumab and comparable with eculizumab among adults with AQP4-IgG+ NMOSD when used as monotherapy. In combination with IST, ravulizumab was more efficacious than satralizumab and comparable to eculizumab.