Treatment with ravulizumab was highly effective in reducing risk for relapse in patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD). No relapses were observed during a median follow-up of 73.5 weeks in the open-label, phase 3, externally controlled CHAMPION-NMOSD trial of ravulizumab.

A placebo-controlled trial studying ravulizumab in NMOSD was deemed unethical because of the availability of eculizumab and other medications, explained Dr. Sean Pittock (Mayo Clinic). A non-inferiority trial was unfeasible due to the rarity of AQP4+ NMOSD. Instead, the CHAMPION-NMOSD trial used the placebo group from the PREVENT trial of eculizumab. Propensity scores were used to account for potential confounders introduced by this comparator. Ravulizumab binds the same complement component, 5-epitope, as eculizumab, but has a longer elimination half-life, allowing for an extended dosing interval of 8, rather than 2, weeks.

Patients aged 18 or older received a weight-based IV loading dose of ravulizumab (2,400-3,000 mg) on day 1, followed by weight-based maintenance doses (3,000-3,600 mg) on day 15 and once every 8 weeks thereafter. The 58 participants on ravulizumab and 47 on placebo had mean follow-up times of 73.5 and 36.0 weeks, respectively.

The study met its primary endpoint, which was time to first adjudicated on-trial relapse and relapse risk reduction (RRR). There were no on-trial relapses in the ravulizumab group versus 20 in the placebo group (P<0.0001), representing an RRR of 98.6%. The percentages of relapse-free participants at 48 weeks were 100% with ravulizumab and 63% with placebo. A key secondary efficacy endpoint, adjudicated on-trial annualized relapse rate (ARR), was 0.00 with ravulizumab (95% upper CI, 0.044). This was superior to a predefined comparator ARR of 0.25, as well as the ARR of 0.42 (95% CI, 0.27–0.66; P<0.0001) in the placebo group. Another key secondary efficacy endpoint, clinically important worsening of the Hauser Ambulation Index (HAI) score, was met by two of 58 participants in the experimental group (3.4%) and by 11 of 47 on placebo (23.4%; OR, 0.16; 95% CI, 0.03-0.77; P=0.023).

Ravulizumab was well tolerated, with a safety profile consistent with that of eculizumab and ravulizumab in other indications. There were no unexpected patterns in the treatment-emergent adverse events, which were reported in 93.1% versus 95.7% of participants in the experimental and placebo group, respectively. Serious adverse events were seen in 13.8% versus 55.3% of participants. There were two cases of meningococcal infection in the ravulizumab group, which recovered with no sequelae. Their occurrence does highlight the need for close monitoring and risk evaluation.

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