Long-Term Eculizumab Treatment Safe and Effective in NMOSD, Real World Data Suggests


Among a cohort of more than 70 individuals with MS, only 1 relapse occurred while on eculizumab, with significant reductions in immunosuppressive use observed.

Ichiro Nakashima, MD, PhD, Tohoku Medical and Pharmaceutical University

Ichiro Nakashima, MD, PhD

Interim data from a regulatory post-marketing surveillance study conducted in Japan showed that eculizumab (Soliris; Alexion) was safe and effective in preventing relapses among patients with aquaporin-4- antibody positive neuromyelitis optica spectrum disorder (NMOSD) over nearly a year’s worth of treatment. Treatment with eculizumab was also associated with a reduction in the concomitant use of immunosuppressive therapies.1

Published in Therapeutic Advances in Neurological Disorders, the findings were consistent with the previously conducted phase 3 PREVENT trial (NCT01892345), in which Japanese participants were low in number. PREVENT, the study that served as the basis for the agent’s FDA approval in 2019, resulted in 98% of eculizumab-treated patients relapse free.

Led by Ichiro Nakashima, MD, PhD, Tohoku Medical and Pharmaceutical University, the safety analysis set of the new study included 71 of 147 patients who had at least 1 case report collected at the interim analysis cutoff. Three patients were excluded from the effectiveness analysis set (n = 68) owing to prior participation in the PREVENT study. At diagnosis of NMOSD, nearly half of the patients in the safety set had symptoms of optic neuritis (47.9%) and half had symptoms of transverse myelitis (49.3%).

At the interim cutoff date, the mean duration of eculizumab treatment was 44.6 (SD, 23.7) weeks, with up to a maximum of 104 weeks observed in the safety analysis set. Most of the cohort (59 of 71; 83.1%) were still on eculizumab at the interim cutoff date, with a smaller portion discontinuing because of adverse events (AEs; n = 3), physician decision (n = 6), patient decision (n = 5), and other (n = 1). AEs were experienced by more than one-fourth (26.8%) of the cohort, with 10 patients reporting adverse drug reactions (ADRs).

Additional safety findings showed 10 serious ADRs experienced by 7 patients, which included 2 cases of pyrexia and 1 case each of cellulitis, bacterial meningitis, herpes meningitis, pneumonia, a streptococcal catheter-related infection, pulmonary hypertension, SLE, and renal impairment. Consistent with PREVENT and its open-label extension, no meningococcal infections were reported among patients with MS.

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In terms of efficacy, 75% (51 of 68) patients experienced at least 1 relapses in the 2 years prior to eculizumab, otherwise a relapse rate of 0.74/person-years (PY), compared with only 1 relapse reported while on treatment, equating to a relapse rate of 0.02/PY. The single relapse experienced during eculizumab was transverse myelitis, however the patient remained on treatment afterward. Of note, the patient had experienced 1 previous relapse in the 2 years prior and had tested negative for the terminal complement protein C5 genetic polymorphism.

"Further data will become available over the course of the 7-year surveillance period to help understand the long-term impact of eculizumab in Japanese patients with AQP4+ NMOSD," the study authors wrote. "In the meantime, these interim results provide important real-world evidence about the safety and effectiveness of eculizumab."

Following initiation of eculizumab the mean daily dose of prednisolone decreased from 16.0 (SD, 4.8) mg/day, observed 24-20 weeks before the study, to 8.6 (SD, 4.8) mg/day at 48-52 weeks after eculizumab and 5.3 (SD, 1.0) mg/day at 100-104 weeks after eculizumab, otherwise a 67.1% overall decrease. From the same time points, the proportion of patients taking more than 10 mg of prednisolone went from 45.6% to 23.1%. The patient who reported a reported had received a decrease in concomitant prednisolone dose after eculizumab initiation, followed by an increase. The dose increase took place following the relapse.

Over the same period, the proportion of patients who were prescribed concomitant immunosuppressive therapies decreased slightly from 54.4% to 47.5%. Intravenous immunoglobulin (IVIg) and plasma exchange were required in 7.4% and 22.1% of patients in the 6 months prior to eculizumab administration. Six months into treatment, no patients were on IVIg and only 1 of the 68 patients (1.5%) required plasma exchange.

1. Nakashima I, Nakahara J, Fujihara K, et al. Long-term safety and effectiveness of eculizumab in patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: a 2-year interim analysis of post-marketing surveillance in Japan. Therapeutic Advances in Neurological Disorders. 2023;16. doi:10.1177.17562864231181177
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