For the majority of patients who were either aquaporin-4-antibody seropositive or seronegative, rituximab was the first disease-modifying therapy administered for neuromyelitis optica spectrum disorder.
Stefan Blum, MD, PhD
(Credit: Princess Alexandra Hospital)
In a retrospective observational study recently published in Multiple Sclerosis Journal – Experimental, Translational and Clinical, findings revealed a significantly lower relapse rate following long-term treatment with rituximab among patients with aquaporin-4-antibody seropositive neuromyelitis optica spectrum disorder (NMOSD). These results suggest that rituximab, at doses lower than previously reported, may be a long-term effective therapy for patients with NMOSD.1
Among 37 patients with NMOSD included in the analysis, 27 of the patients were AQP4-IgG-seropositive and 10 of the patients were seronegative; the majority were women (seropositive, 96%; seronegative, 60%). Investigators observed a significant reduction of annualized relapse rates (ARRs) post-rituximab for both groups of patients compared with pre-rituximab (post-rituximab, 0.136; 95% CI 0.088–0.201 vs pre-rituximab, 0.366; 95% CI, 0.271–0.483; P <.001). Notably, authors reported a significantly lower ARR for the seropositive group (p < 0.001); with the pre-rituximab ARR at 0.375 (95% CI, 0.264–0.517) and the post-rituximab ARR at 0.097 (95% CI, 0.053–0.163).
“The results of this study suggest that rituximab may be an effective therapy for NMOSD at lower doses than initially reported. Rituximab was associated with a significantly reduced relapse rate in the whole cohort and seropositive subgroup, but significance was not reached for the seronegative subgroup,” senior author Stefan Blum, MD, PhD, a neurologist at Mater Hospital in Brisbane and an associate professor at Princess Alexandra Hospital in Australia, and colleagues, wrote.1“This may be due to the small cohort of seronegative patients and a greater degree of disease heterogeneity in this cohort.”
Investigators in the study examined a cohort of patients diagnosed with AQP4-IgG-seropositive and seronegative NMOSD2 who were treated with rituximab at 2 major tertiary hospitals in Brisbane, Australia. The focus was on exploring the dosing of rituximab and assessing its efficacy and safety in this patient population. Authors evaluated ARRs before and during rituximab treatment and also measured disability using Modified Rankin Scores (mRS). Patients received a rituximab dose at either 500 mg or 1000 mg as 2 separate 500 mg infusions 2 weeks apart. The median number of doses for rituximab was 10 (IQR, 6–14) for the seropositive group and 6 (IQR, 4–14) in the seronegative group; median follow-up was 59 months (IQR, 34–95) and 39 months (19–62), respectively.
Researchers reported that the mean age at the first infusion of rituximab among the participants was 45 years in the seropositive group (SD, 12) and 35 years (SD, 13) in the seronegative group. Additionally, investigators noted that the median disease duration at rituximab initiation was 20 months for the seropositive group (IQR, 4–68) and 8 months for the seronegative group (IQR, 4–84). For both groups in the cohort, the median mRS was 2 (IQR, 1–3) prior to rituximab and improved to 1 (IQR, 1–2) at the time of last follow-up (P <.001). Blum et al noted that, “This is an encouraging finding in light of the long follow-up durations, where aging and medical comorbidities can begin to impair function.”1
As for safety findings, allergic reactions led to rituximab cessation among 2 patients (5%) and infections occurred in 32% of the cohort, which were mostly mild, but included 1 fatal urosepsis case and severe SARS-CoV-2 pneumonia in an unvaccinated patient. Additional results showed that mild secondary hypogammaglobulinemia was reported in 3 patients (8%), with 1 patient who needed IVIg for recurrent infections. Moreover, 3 patients developed malignancies after starting rituximab, and the treatment was stopped in 4 patients (11%) because of adverse events, including allergic reactions, liver cirrhosis, and acute myeloid leukemia.
“The ability to make direct comparisons between our study and prior studies involving higher doses of rituximab is limited for a number of reasons, including the retrospective nature of the majority of studies and variations in the proportion of patients exposed to other immunosuppressive agents,” Blum et al noted.1 “However, our study does suggest both efficacy and a favorable safety profile when rituximab is administered at the lower dose of 500 mg, with a relatively small proportion of patients developing hypogammaglobulinaemia and infections.”
