Inebilizumab vs Low-Dose Rituximab In NMOSD

Key Takeaways

• In NMOSD, inebilizumab was associated with fewer relapses and more favorable relapse-free survival and adjusted relapse burden over 12 months.
• Relapse-associated EDSS worsening was less frequent, and overall EDSS improvement favored inebilizumab, although that improvement was not maintained after excluding baseline EDSS 2.0 or lower.
• Infections were less common with inebilizumab, while overall adverse-event and serious-adverse-event rates were not significantly different and infusion reactions were uncommon in both groups.

In a retrospective-prospective multicenter cohort of AQP4-IgG–positive NMOSD across six Chinese cities, investigators compared inebilizumab with a low-dose rituximab regimen. Over 12 months, relapses occurred in 8 of 119 patients receiving inebilizumab and 24 of 110 receiving low-dose rituximab.

The cohort included 229 patients, with 119 receiving inebilizumab and 110 receiving low-dose rituximab, and median follow-up was 12.0 months in both groups. Inebilizumab was given as 300 mg on days 1 and 15, then every 6 months, while rituximab used a 100/500/500 mg induction regimen and CD19-guided 500 mg retreatment. Adjusted annualized relapse rates were 0.06 with inebilizumab and 0.24 with low-dose rituximab, with an IRR of 3.65 (95% CI 1.59–8.39; p = 0.003) for low-dose rituximab versus inebilizumab. One-year relapse-free survival was 93.60% and 77.60%, respectively.

Relapse-associated EDSS worsening was recorded in 2 inebilizumab recipients and 7 low-dose rituximab recipients, with higher odds in the low-dose rituximab group (OR 8.16, 95% CI 1.44–46.36; p = 0.018), although the confidence interval was wide. Overall EDSS improvement was seen in 65 of 119 patients, or 54.62%, with inebilizumab and 39 of 110, or 35.45%, with low-dose rituximab. That comparison yielded lower odds of EDSS improvement with low-dose rituximab (OR 0.36, 95% CI 0.18–0.72; p = 0.004). After excluding patients with baseline EDSS 2.0 or lower, improvement rates were 40.34% and 33.64%, with no significant between-group difference (p = 0.339). Some low-dose rituximab relapses occurred within 2 to 6 months, and some inebilizumab relapses followed delayed or missed infusions.

Adverse events affected 35 of 119 patients receiving inebilizumab, accounting for 45 events, and 44 of 110 receiving low-dose rituximab, accounting for 58 events (p = 0.097). Infections occurred in 10 of 119 patients with inebilizumab and 25 of 110 with low-dose rituximab (p = 0.003). Infusion-related reactions were uncommon and all grade 1–2, at 3.36% and 5.45%, and serious adverse events occurred in 2 and 4 patients, respectively (p = 0.431). Severe events included one grade 4 pneumonia with inebilizumab, one severe urinary tract infection with low-dose rituximab, and one death after recurrent NMOSD with acute respiratory failure. No death was attributed to an adverse event, and this Class III evidence reflects a 12-month window, missing data, possible underreporting of mild events, and limits beyond the low-dose rituximab protocol.