Infection Risk in Patients with Complement-Mediated Neurological Disorders Receiving Eculizumab: Findings from Two Phase 3 Studies and Their Extensions in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (AQP4+NMOSD) and Acetylcholine-Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis (AChR plus gMG)

Objective: To review, in two complement-mediated neurological disorders, the risk of infection in patients treated with eculizumab versus placebo, with or without concomitant immunosuppressant therapy (IST). Background: PREVENT (NCT01892345) and REGAIN (NCT01997229) were phase 3, randomized, double-blind studies with open-label extensions (NCT02003144 [interim data] and NCT02301624), comparing the safety and efficacy of eculizumab and placebo in patients with AQP4+ NMOSD and AChR+ gMG, respectively. Design/Methods: Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo, with stable-dose concomitant ISTs permitted. We report pooled post hoc infection data from these studies and for subgroups determined by number of ISTs (0, 1, 2 or ≥3 ISTs) used at baseline. Results: Rates (per 100 patient-years [PY]) and types of infection were similar in eculizumab and placebo groups. In patients with NMOSD, rates/100PY and %(n/N) were: no ISTs, 192.1, 77.1%(27/35) versus 192.2, 61.5%(8/13); 1 IST, 183.6, 72.7%(40/55) versus 154.1, 63.6%(14/22); 2 ISTs, 195.1, 80.9%(38/47) versus 266.7, 83.3%(10/12); no patients used ≥3 ISTs. For patients with gMG: no ISTs, 238.2, 100.0%(2/2) versus 305.6, 50.0%(1/2); 1 IST, 230.6, 82.9%(34/41) versus 253.1, 50.0%(9/18); 2 ISTs, 171.7, 91.0%(71/78) versus 192.5, 58.5%(24/41); ≥3 ISTs, 98.0, 50.0%(1/2) versus 100.1, 50.0%(1/2). For serious infections in the NMOSD and gMG groups and for patients receiving eculizumab versus placebo, respectively: no ISTs, 1.4, 2.9%(1/35) versus 8.0, 7.7%(1/13) and none observed; 1 IST, 13.9, 14.5%(8/55) versus 7.0, 9.1%(2/22) and 16.3, 24.4%(10/41) versus 34.5, 5.6%(1/18); 2 ISTs, 15.1, 27.7% (13/47) versus 47.6, 25.0%(3/12) and 13.4, 21.8%(17/78) versus 24.1, 12.2%(5/41); ≥3 ISTs, for gMG, 14.0, 50.0%(1/2) versus 0.0, 0.0%(0/2). Conclusions: In these neurologic indications, the overall risk and the types of infections were similar in eculizumab and placebo groups, regardless of concomitant IST use. These findings are consistent with the established safety profile for eculizumab in other indications. Disclosure: Dr. Levine has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Griffons, Alexion, Nufactor, Diplomat, Shire, Corinthian Reference Labs. Dr. Levine holds stock and/or stock options in Corinthian Reference Labs, Cutaneous Neurodiagnostics. Dr. Levine has received research support from PTC Therapeutics, Sun Pharmaceuticals, Actinogen. Dr. Mantegazza has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Argenx Pharma, Biomarin. Dr. Mantegazza has received research support from Alexion Pharmaceuticals, Argenx Pharma, Biomarin. Dr. Oreja Guevara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honoraria for speaking and/or consultancy from Biogen, Sanofi- Genzyme, Merck, Roche, Teva, and Novartis. Dr. Carrillo-Infante has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Carrillo-Infante holds stock and/or stock options in Alexion Pharmaceuticals (Employee) which sponsored research in which Dr. Carrillo-Infante was involved as an investigator. Dr. Kaprielian has nothing to disclose. Dr. Shang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Shang holds stock and/or stock options in Biogen. Dr. Yountz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Yountz holds stock and/or stock options in Alexion Pharmaceuticals (Employee) which sponsored research in which Dr. Yountz was involved as an investigator. Dr. Howard holds stock and/or stock options in Johnson \u0026 Johnson, Pfizer, and General Electric. Dr. Howard has received research support from Alexion Pharmaceuticals, Argenx BVBD, and Ra Pharmaceuticals.