Switching from rituximab to C5 complement inhibitors is safe in AQP4+ NMOSD

Many patients with aquaporin (AQP)4 IgG seropositive (AQP4+) neuromyelitis optica spectrum disorders (NMOSD) used rituximab prior to transitioning to C5 complement inhibitors (C5ITs). In these patients, safety outcomes in the PREVENT and CHAMPION-NMOSD studies were not different from patients who had not received prior rituximab. This is important to know for patients and caregivers when considering a switch from rituximab to C5IT.

Rituximab is often prescribed off-label in the early stages of AQP4+ NMOSD. However, patients often need to switch to more efficacious therapies to prevent relapse, most notably C5ITs like eculizumab and ravulizumab.

The phase 3 studies PREVENT (NCT01892345) and CHAMPION-NMOSD (NCT04201262) evaluated the safety and efficacy of eculizumab and ravulizumab, respectively, in adult patients with AQP4+ NMOSD [1,2]. A pooled post-hoc analysis compared safety outcomes between patients who had and had not received prior rituximab treatment within 3–12 months of starting a C5IT [3]. The authors analysed treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and deaths or withdrawals due to TEAEs.

Of the 154 actively treated patients in PREVENT and CHAMPION-NMOSD, 38 (24.7%) had used rituximab within 3–12 months prior to the first C5IT dose, whereas 116 (75.3%) had not. In both groups, the mean number of relapses in the year prior to screening for the trial was 2.0; they also had similar historical annualised relapse rates.

The incidence of patients experiencing TEAEs and TESAEs was generally similar in patients with prior and no prior rituximab use: TEAEs 94.7% versus 90.5%, and TESAEs 21.2% versus 24.1%, respectively. Most TEAEs were mild or moderate in severity and deemed unrelated to the C5IT. The most common types of TEAE were infection and infestation: 71.1% versus 71.6%, respectively. Headache and upper respiratory tract infections were more common in patients with no prior rituximab use, while urinary tract infection occurred more frequently in patients with prior rituximab exposure. In the prior-rituximab group, 15 of 413 events were TESAEs; 13 were considered unrelated to the study drug. No patients experienced a TEAE or TESAE leading to C5IT withdrawal in this group.

1. Pittock SJ, et al. Ann Neurol. 2023;93:1053–1068.
2. Pittock SJ, et al. N Engl J Med. 2019;381:614–625.
3. Levy M, et al. Safety findings in patients with AQP4+ NMOSD who received eculizumab or ravulizumab in the PREVENT and CHAMPION-NMOSD studies and had received rituximab within 1 year prior to enrolment. P378, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December 2023