Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease that typically affects the optic nerves and spinal cord.1,2 At least two-thirds of cases are associated with aquaporin-4 (AQP4) antibodies and complement-mediated damage to the central nervous system.2 At the ECTRIMS 2021 meeting, Dean Wingerchuk, Director of the Mayo Clinic Division of Multiple Sclerosis and Autoimmune Neurology (Arizona, United States) presented findings on the long-term efficacy and tolerability of eculizumab, a complement inhibitor, for the treatment of AQP4-positive NMOSD. Prof. Wingerchuk talked about the PREVENT open-label extension (OLE) study, and presented early, real-world evidence on eculizumab treatment in AQP4-positive NMOSD.
The PREVENT OLE study – Objective
Patients who had completed the PREVENT trial or had a physician-determined relapse during the study were able to enrol in the OLE (maximum duration: 5.5 years). They received 1200 mg (intravenous) eculizumab every 2 weeks, after a blinded induction phase, and were allowed to continue on immunosuppressant therapy (IST). The primary objective was to assess long-term safety; secondary outcomes were annualised relapse rate (ARR), disability, and quality of life.
Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease that typically affects the optic nerves and spinal cord.1,2 At least two-thirds of cases are associated with aquaporin-4 (AQP4) antibodies and complement-mediated damage to the central nervous system.2 At the ECTRIMS 2021 meeting, Dean Wingerchuk, Director of the Mayo Clinic Division of Multiple Sclerosis and Autoimmune Neurology (Arizona, United States) presented findings on the long-term efficacy and tolerability of eculizumab, a complement inhibitor, for the treatment of AQP4-positive NMOSD. Prof. Wingerchuk talked about the PREVENT open-label extension (OLE) study, and presented early, real-world evidence on eculizumab treatment in AQP4-positive NMOSD.
The PREVENT OLE study – Objective
Patients who had completed the PREVENT trial or had a physician-determined relapse during the study were able to enrol in the OLE (maximum duration: 5.5 years). They received 1200 mg (intravenous) eculizumab every 2 weeks, after a blinded induction phase, and were allowed to continue on immunosuppressant therapy (IST). The primary objective was to assess long-term safety; secondary outcomes were annualised relapse rate (ARR), disability, and quality of life.
Eculizumab was effective irrespective of concomitant immunosuppressant therapy
Prof. Wingerchuk explained that in the PREVENT OLE study, benefits in terms of efficacy were seen irrespective of concomitant IST. At 192 weeks (3.7 years), 96.2% of patients with eculizumab monotherapy and 93.8% with combination therapy (i.e. eculizumab with IST) remained relapse free, which Prof. Wingerchuk described as excellent results. There was also a consistent trend to improvement in the Expanded Disability Status Scale (EDSS) score (over 1 year), irrespective of whether participants previously received eculizumab in the PREVENT trial. Prof. Wingerchuk illustrated the efficacy of eculizumab by describing the journey of a patient whose ARR was very high at >4 before entering the PREVENT study. After initiation of eculizumab treatment, the patient’s ARR decreased to zero. The patient remains in the PREVENT OLE and has been relapse free for over 3 years.
Safety of eculizumab treatment
Moving on to safety, Prof. Wingerchuk noted that most adverse events were consistent across the PREVENT placebo and the combined eculizumab groups. He explained that across PREVENT and the OLE, proportions with treatment-related adverse events (TRAEs) were similar between the PREVENT placebo group and the combined eculizumab group (57.4% versus 62.0%, respectively). Rates of TRAEs were 167.5/100 patient-years (PY) in the PREVENT placebo group and 183.5/100 PY in the combined eculizumab group; rates of treatment-related serious adverse events (SAEs) were 24.5/100 PY and 8.6/100 PY, respectively. SAEs occurring in more than one patient included pneumonia (in five patients), urinary tract infection (in four patients), cellulitis (in two patients), and sepsis (two patients). No patient developed a meningococcal infection (eculizumab increases susceptibility to encapsulated organisms) – one patient developed a Neisseria gonorrhoeae infection (which resolved with antibiotic treatment).
Real-world evidence
Prof. Wingerchuk went on to discuss data from a real-world study on eculizumab in Japan, where there is a mandatory post-marketing surveillance programme on eculizumab in relapsing AQP4-positive NMOSD. Seventy-nine patients registered in this study (with data collection between November 2019 and April 2021). The safety analysis set included 20 patients with at least one case report form; three patients who participated in the PREVENT trial were excluded, leaving 17 in the effectiveness analysis set (with 10.7 PY of treatment and a mean duration of illness of 9.2 years). Prof. Wingerchuk explained that in the 2 years before starting eculizumab treatment, 12 patients experienced 22 relapses (ARR of 0.65). No relapses were reported from eculizumab initiation up to the data cut-off (ARR of 0.00). Safety data were favourable and were considered to be consistent with the PREVENT study; 15% of patients experienced any type of adverse event and there was one TRAE of eyelid oedema and erythema. There were no serious TRAEs and no meningococcal infections.
Conclusion
In summary, Prof. Wingerchuck presented data from the PREVENT trial and its OLE, which suggest that eculizumab has a favourable long-term benefit-risk profile in AQP4-positive NMOSD. Additionally, Prof. Wingerchuck presented emerging real-world data from Japan which are consistent with these findings.
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References
- Hor JY et al. Front Neurol. 2020;11:501
- Pittock SJ et al. N Engl J Med. 2019;381:614–25
- Gómez-Cibeira E, et al. Neurology 2016;86:399-400
- Nakashima I, et al. ECTRIMS 2021 (digital). Abstract #P973; E-poster.
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