Ravulizumab Shows Greater Efficacy for Relapse Prevention in NMOSD

Among patients with anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD), ravulizumab vs other approved NMOSD treatments is superior in efficacy for the prevention of relapse, according to study findings published in Neurology and Therapy.

A rare neuroinflammatory condition called AQP4-Ab+ NMOSD causes unpredictable, relapsing attacks on the central nervous system (CNS) leaving permanent damage. Ravulizumab, a humanized monoclonal antibody complement inhibitor, has been recently approved in the United States to treat patients with this condition. Researchers conducted a network meta-analysis (NMA) to compare ravulizumab to other established NMOSD therapies.

The researchers used the Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials conducted in adult patients with AQP4-Ab+ NMOSD. The study interventions included ravulizumab, eculizumab, satralizumab, and inebilizumab. The primary endpoint was the amount of time to the first relapse. The other endpoint present in most studies was the annualized relapse rates (ARRs). 

A total of 442 citations were screened for inclusion, with 17 citations associated with 5 clinical trials included in the final analysis:

• (CHAMPION-NMOSD [ClinicalTrials.gov Identifier: NCT04201262],
• PREVENT [ClinicalTrials.gov Identifier: NCT01892345],
• N-MOmentum [ClinicalTrials.gov Identifier: NCT02200770],
• SakuraSky [ClinicalTrials.gov Identifier: NCT02028884], and
• SakuraStar [ClinicalTrials.gov Identifier: NCT02073279]).

Of the 4 trials that reported both time-to-first relapse and ARR in monotherapy, the researchers found that patients treated with ravulizumab vs inebilizumab were 91% less likely to have a first relapse (hazard ratio [HR], 0.09; 95% credible interval [CrI], 0.02-0.57). Additionally, patients treated with ravulizumab vs satralizumab were 92% less likely to have a first relapse (HR, 0.08; 95% CrI, 0.01-0.55). 

Patients on ravulizumab had an 98% lower ARR (rate ratio [RR], 0.02; 95% CrI, 0.00-0.38) compared inebilizumab (RR, 0.02; 95% Crl, 0.00-0.38) and satralizumab (RR, 0.02; 95% CrI, 0.00-0.42). The treatment effects and ARR of ravulizumab were comparable to that of eculizumab. 

A total of 3 trials reported time-to-first relapse and ARR results of combination therapies. Combination therapy with ravulizumab and immunosuppressive therapy (IST) showed an 85% decreased chance of experiencing first relapse compared to patients with satralizumab and IST (HR, 0.15; 95% CrI, 0.03-0.78). While combination therapy of ravulizumab and IST showed improvements in treatment effects in ARR, there is uncertainty in the relative treatment-effect estimates and it cannot be determined that this treatment is superior to other alternatives.

Among 4 trials reporting time-to-first relapse for both monotherapy and combination therapy, the researchers found that patients on ravulizumab with or without IST had a 94% decreased chance of having a first relapse compared to patients on satralizumab with or without IST (HR, 0.06; 95% CrI, 0.02-0.18). 

Patients taking ravulizumab with or without IST had a 76% decreased chance of first relapse when compared to patients on eculizumab with or without IST (HR, 0.24; 95% Crl, 0.08-0.71), while the results of ARR were comparable. Patients taking ravulizumab with or without IST showed an ARR 98% lower than patients taking satralizumab with or without IST. 

Study limitations included a small sample size, not conducting an NMA with safety endpoints, and a lack of long-term follow-up data. 

“Although efficacy is only one consideration when making treatment decisions, knowledge of the comparative efficacy effects between treatments is a vital component in the shared decision-making process,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.