Ravulizumab Outperforms NMOSD Therapies in Preventing Relapse, Meta-Analysis Reveals


A recent network analysis of clinical trials demonstrated that ravulizumab exhibited greater efficacy in preventing relapse in patients with NMOSD compared with other treatments.

Stacey L. Clardy, MD, PhD  (Credit: University of Utah)

Stacey L. Clardy, MD, PhD

(Credit: University of Utah)

Newly published in Neurology and Therapy, a network analysis of randomized controlled trials revealed that ravulizumab (Ultomiris; Alexion) was superior in efficacy for relapse prevention in patients with anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in comparison with other approved treatments with different methods of action.1 This comparative efficacy analysis of new NMOSD therapies, such as ravulizumab, and other established therapies allow clinicians to make better informed treatment decisions for their patients.

Findings in the analysis revealed that ravulizumab was associated with a lower risk of relapse in comparison with either inebilizumab (Uplizna; Horizon Therapeutics)(HR 0.09; 95% CrI, 0.02-0.57) or satralizumab (Enspryng; Genentech) (HR, 0.08; 95% CrI, 0.01-0.55). Recently presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, by lead author Stacey L. Clardy, MD, PhD, an autoimmune neurologist and associate professor at the University of Utah, results showed that ravulizumab was comparable to eculizumab (Soliris; Alexion), a similarly acting complement C5 inhibitor, in terms of lowered risk of relapse (HR, 0.86; 95% Crl, 0.16-4.52).2

Top Clinical Takeaways

  • Ravulizumab showed significant efficacy in preventing relapse in patients with NMOSD, particularly when combined with immunosuppressive therapy.
  • The study underscored the importance of comparative efficacy analyses in guiding treatment decisions.
  • Limitations such as sample size and heterogeneity in trial characteristics highlight the need for further research to validate these findings.

In this Bayesian network meta-analysis, investigators assessed the efficacy of ravulizumab relative to established AQP4-Ab+ NMOSD treatments. The data for the analysis were extracted from trials identified by a systematic literature review which consisted of 17 publications representing 5 unique and global studies including PREVENT (NCT01892345), N-MOmentum (NCT02200770), SAkuraSky (NCT02028884), SAkuraStar (NCT02073279), and CHAMPION-NMOSD (NCT04201262). The primary end point for this network analysis was time-to-first relapse and other outcomes included annualized relapse rates (ARRs).

READ MORE: Combination Therapy of Corticosteroids and Immunosuppressants Shows Efficacy in Rare Case of Overlapping CIDP and NMOSD

Additional findings showed that ravulizumab in combination with immunosuppressive therapy (IST) was associated with a lower risk of relapse compared with satralizumab plus IST (HR, 0.15; 95% CrI, 0.03-0.78). Notably, when comparing eculizumab plus IST, results suggested no difference in terms of relapse risk. Authors also noted that there were no patients treated with inebilizumab who received background IST and thus were not included in the analysis. Furthermore, researchers reported that the ARR with ravulizumab monotherapy was 98% lower compared with inebilizumab (RR, 0.02; 95% Crl, 0.00-0.38) and satralizumab (RR, 0.02; 95% Crl, 0.00-0.42) monotherapies. Overall, authors noted that ARR with ravulizumab plus IST showed the strongest treatment-effect estimates compared with the other treatment interventions.

All told, a limitation of the study included that each treatment group was informed by only a single trial or 2 trials with a limited sample size. Thus, researchers had limited ability to account for heterogeneity in the analysis’ estimates and prevent any cross-trial adjustment of patient characteristics. In addition, authors noted that there were no long-term follow-up data from the trials incorporated. Despite similarly defined outcomes of interest across the included studies, investigators noted discrepancies in enrollment criteria such as NMOSD relapse activity inclusion criteria and relapse definition criteria.

Ravulizumab, a complement C5 inhibitor, was approved for the treatment of patients who are AQP4 NMOSD in March 2024. With the decision, it became the fourth approved therapy, following behind eculizumab, inebilizumab, and satralizumab. Ravulizumab’s approval was based on CHAMPION-NMOSD, where the agent met its primary end point of time to first on-trial relapse, with no relapses observed in 58 patients with NMOSD over a median treatment duration of 73 weeks.3 CHAMPION-NMOSD used an external placebo control arm from PREVENT, a phase 3 study that evaluated eculizumab.

New interim data presented at AAN 2024 from the open-label extension of the CHAMPION-NMOSD trial, showed that no patients treated with ravulizumab experienced an adjudicated relapse over a 138.4-week median follow-up.4 In addition, most patients (91.4%; 53 of 58) had improved HAI score, and most (91.4%; 53 of 58) had no clinically important worsening in Expanded Disability Status Scale score. The analysis, led by Sean Pittock, MD, demonstrated the long-term clinical benefit of ravulizumab in AQP4+ NMOSD.

Pittock, director of the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, sat down with NeurologyLive® to discuss the safety profile of ravulizumab and specifically, the risk of meningococcal infection. He discussed the importance of following the medication close to its label description and why patients should have appropriate vaccinations before receiving the therapy. Furthermore, Pittock stressed this can be an effective and well-tolerated therapy when administered correctly.

1. Clardy SL, Pittock SJ, Aktas O, et al. Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder. Neurol Ther. Published online May 9, 2024. doi:10.1007/s40120-024-00597-7
2. Clardy S, Pittock S, Aktas O, et al. Indirect treatment comparison of ravulizumab versus approved treatment options for adults with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD). Presented at: 2024 AAN Annual Meeting; April 13-18; 002511
3. ULTOMIRIS® (ravulizumab-cwvz) approved in the US for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD). News Release. Alexion Pharma. Published March 25, 2024. Accessed May 13, 2024. https://www.businesswire.com/news/home/20240325711806/en/ULTOMIRIS%C2%AE-ravulizumab-cwvz-approved-in-the-US-for-the-treatment-of-adults-with-neuromyelitis-optica-spectrum-disorder-NMOSD
4. Pittock S, Barnett M, Bennett J, et al. Efficacy and safety of ravulizumab in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD): interim analysis from the ongoing phase 3 CHAMPION-NMOSD trial. Presented at: 2024 AAN Annual Meeting; April 13-18; ABSTRACT 002489
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