A recent retrospective cohort analysis suggests newer NMOSD-specific treatments may offer improved efficacy and safety compared with rituximab and commonly used off-label therapies.
A recent real-world study reported that FDA-approved therapies, including eculizumab (Soliris; Alexion) inebilizumab (Uplizna; Amgen), and satralizumab (Enspryng; Genentech), were associated with significantly lower relapse risk and fewer serious adverse events (AEs) compared with rituximab in patients with
In the analysis, researchers included a total of 176 patients with NMOSD who were followed for a median of 9 years (interquartile range, 5-14), contributing to 691 relapse assessments. Notably, the median age at first attack was 42 years, and 83% of patients were women. Findings showed that a 5-year relapse-free probability was 69.7% with rituximab, compared with 100% for C5 inhibitors, inebilizumab, and satralizumab, 51.1% for MMF, and 35.3% for azathioprine.
Additional efficacy findings demonstrated that C5 inhibitors were associated with a lower risk of relapse compared with rituximab (HR, 0.12; 95% CI, 0.07–0.24), as were inebilizumab (HR, 0.22; 95% CI, 0.12–0.65) and satralizumab (HR, 0.19; 95% CI, 0.11–0.42). Authors reported that annualized relapse rates (ARR) were 0.08 for rituximab (95% CI, 0.062–0.10), 0 for C5 inhibitors (95% CI, 0–0.062), 0 for inebilizumab (95% CI, 0–0.06), 0 for satralizumab (95% CI, 0–0.17), 0.19 for MMF (95% CI, 0.14–0.26), and 0.34 for azathioprine (95% CI, 0.18–0.56).
“This study provides insights into the comparative effectiveness and safety of NMOSD treatments in a real-world setting. Among the FDA-approved drugs, C5 inhibitors had the highest patient-years in our cohort and showed both superior relapse prevention and lower rates of serious adverse events (including serious infection requiring hospitalization) compared with rituximab, whereas MMF and azathioprine had higher rates than rituximab,” lead author
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Modern NMOSD Management: Evidence, Safety, and Treatment Selection
In this 5-part panel discussion series, Shamik Bhattacharyya, MD, and Philippe-Antoine Bilodeau, MD, unpack their recent real-world comparative effectiveness study published in Neurology.
Researchers compared the efficacy and safety of rituximab-the most commonly used treatment-with recently approved NMOSD-specific treatments and other common off-label NMOSD treatments. Patients included in the analysis met the 2015 International Panel for NMO Diagnosis criteria for NMOSD,2 and had been assessed in person by a Mass General Brigham neurologist between January 1, 2000, and June 30, 2024. Authors noted that the primary outcomes are relapse-free survival and ARR, with secondary outcomes being serious infectious adverse event (SIAE) and treatment-limiting adverse event (TLAE)-free survival.
In the study, the frequency of AEs was assessed for each treatment period. Among rituximab treatment periods, 13% were associated with hypogammaglobulinemia, 34% with mild infections (eg, urinary tract infections, upper respiratory tract infections), 28% with serious infections (eg, bacterial pneumonia, infections requiring intravenous antibiotics), and 6.3% with hypersensitivity reactions. Compared with rituximab, results showed that C5 inhibitors were associated with a lower incidence of SIAEs, with an incidence rate ratio of 0.17 (95% CI, 0.06–0.43; P = .0002).
A composite end point incorporating time to first relapse, SIAEs, or TLAEs was also evaluated to assess efficacy, safety, and tolerability. At 5 years, the probability of remaining free from relapse, SIAEs, or TLAEs was 55% for rituximab, 91% for C5 inhibitors, 19% for azathioprine, and 35% for MMF. Owing to shorter follow-up duration, 3-year data were reported for satralizumab and inebilizumab, with event-free probabilities of 79% and 38%, respectively.
Data in the combined end point also demonstrated that C5 inhibitors were associated with a reduced risk of relapse, SIAEs, or TLAEs compared with rituximab (HR, 0.22; 95% CI, 0.05–0.67). In contrast, researchers reported that azathioprine (HR, 2.33; 95% CI, 1.08–4.86) and MMF (HR, 1.75; 95% CI, 1.02–2.95) were associated with increased risk relative to rituximab. No statistically significant differences in risk were observed for inebilizumab (HR, 1.23; 95% CI, 0.24–3.12) or satralizumab (HR, 1.01; 95% CI, 0.16–2.68) compared with rituximab.
“We also found that nearly half of the patients on rituximab experienced a relapse or significant side effect within 5 years. In jurisdictions where other treatments are available, we caution against using rituximab first-line in NMOSD. We also recommend against the use of MMF and azathioprine,” Bilodeau et al noted. “These findings emphasize the importance of optimizing treatment selection to reduce the burden of relapses and serious complications. Comparative effectiveness trials with composite endpoints that incorporate relapses and safety are needed to comprehensively compare NMOSD treatments.”
