Long-term safety and efficacy of Eculizumab in Aquaporin-4 IgG-positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088–109

No-reflow phenomenon in the cerebral circulation of the gerbil.

The no-reflow phenomenon has been produced in the cerebral hemispheres of the gerbil by 30 minutes of bilateral carotid artery occlusion. The no-reflow phenomenon was found to develop in relation to the fall in blood pressure which occurred on release of bilateral carotid clips. Metaraminol tartrate intravenously prevented the fall of blood pressure and significantly reduced the occurrence of the no-reflow phenomenon. Metaraminol tartrate, however, did not alter the morbidity or mortality of carotid artery occlusion for 30 minutes. There is thus no support from these experiments for the view that the no-relow phenomenon plays an important functional role in the reversibility of the effects of severe cerebral ischaemia

Current concepts in multiple sclerosis therapy

Over the past 20 years, the available therapies for multiple sclerosis have expanded exponentially. With several more agents likely to be approved for public funding in Australia in the next 12 months on top of the existing multitude of Australian Pharmaceutical Benefits Scheme-subsidized therapies, the choice is becoming even more complex. This review summarizes the current state of available therapies and anticipates likely future directions, including an important focus on contemporary symptom management. For each agent, the major trials, side effects, and clinical utility are summarized, with a particular focus on the Australian experience of these therapies. It is hoped this review provides an up-to-date reference of the exciting current state of multiple sclerosis therapy