Safety of eculizumab in MG and NMOSD – analysis of the phase 3 studies REGAIN and PREVENT and their extensions

Topic:

Clinical Trials

Poster Number: 78

Author(s):

James F. Howard MD, FAAN, Todd Levine MD, Celia Oreja-Guevara MD, PhD, Cynthia Carrillo-Infante , Eva Laudon-Meyer MD, PhD, Shulian Shang PhD, Sean J. Pittock MD, Renato Mantegazza MD

Institutions:

1. University of North Carolina at Chapel Hill, NC, USA, 2. Phoenix Neurological Associates, 3. Hospital Universitario Clínico San Carlos, 4. Alexion Pharmaceuticals, 5. Alexion Pharmaceuticals, 6. Alexion Pharmaceuticals, 7. Mayo Clinic, Rochester, 8. Fondazione IRCCS, Istituto Neurologico Carlo Besta

Background:
Acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG) and aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) are complement-mediated autoimmune diseases. Eculizumab (terminal complement inhibitor) elicited clinical improvements and reduced relapse risk in randomized, double-blind, phase 3 studies and their open-label extensions (OLEs) of AChR+ gMG (REGAIN NCT01997229/OLE NCT02301624) and AQP4+ NMOSD (PREVENT NCT01892345/OLE [interim data] NCT02003144).
Objectives:
To compare infection rates in patients receiving eculizumab vs placebo, with/without permitted immunosuppressive therapies (ISTs), during REGAIN, PREVENT, and their OLEs.
Methods:
Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Post hoc analysis examined infection rates overall and by number of baseline ISTs.
Results:
In eculizumab vs placebo groups, in patients with gMG and those with NMOSD, respectively, infection rates/100 patient-years (PY), % (n/N) were: no IST: 236.8, 100.0% (2/2) vs 305.6, 50.0% (1/2) and 176.1, 80.0% (28/35) vs 192.2, 61.5% (8/13); one IST: 228.8, 82.9% (34/41) vs 253.1, 50.0% (9/18) and 171.5, 81.8% (45/55) vs 154.1, 63.6% (14/22); two ISTs: 170.5, 91.0% (71/78) vs 192.5, 58.5% (24/41) and 186.7, 85.1% (40/47) vs 238.2, 83.3% (10/12); ≥3 ISTs (gMG): 97.5, 50.0% (1/2) vs 100.1, 50.0% (1/2). Serious infection rates/100 PY, % (n/N) were: no IST: none observed (0/2 vs 0/2) and 2.3, 5.7% (2/35) vs 8.0, 7.7% (1/13); one IST: 16.2, 24.4% (10/41) vs 34.5, 5.6% (1/18) and 11.2, 16.4% (9/55) vs 7.0, 9.1% (2/22); two ISTs: 13.4, 21.8% (17/78) vs 24.1, 12.2% (5/41) and 14.8, 29.8% (14/47) vs 47.6, 25.0% (3/12); ≥3 ISTs (gMG): 13.9, 50.0% (1/2) vs 0.0, 0.0% (0/2). One patient with gMG (two ISTs) had meningococcal meningitis, but resumed eculizumab following successful antibiotic therapy.
Conclusions:
In AChR+ gMG and AQP4+ NMOSD, infection rates were similar in eculizumab and placebo groups, regardless of concomitant ISTs, and were consistent with eculizumab’s established safety profile.