LONG-TERM EFFICACY OF ECULIZUMAB IN REFRACTORY GENERALIZED MYASTHENIA GRAVIS: RESPONDER ANALYSES


Topic:

Clinical Trials

Poster Number: 55

Author(s):

James Howard, MD, FAAN, Chafic Karam, MD, Marcus Yountz, MD, Fanny O’Brien, PhD, Tahseen Mozaffar, MD

Institutions:

1. University of North Carolina at Chapel Hill, NC, USA, 2. Oregon Health and Science University, Portland, OR, USA, 3. Alexion Pharmaceuticals, Boston, MA, USA, 4. Alexion Pharmaceuticals, Boston, MA, USA, 5. University of California Irvine

Background
The 6-month double-blind placebo-controlled REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) demonstrated the sustained effectiveness of the terminal complement inhibitor eculizumab in adult patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG).
Objective
To analyze response profiles in REGAIN and its OLE.
Approach
The analysis was conducted using Myasthenia Gravis–Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores recorded during REGAIN and its OLE. Early/late responses were defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) occurring at ≤12/>12 weeks, respectively, after baseline (eculizumab initiation).
Results
The analysis included 98 patients. By Week 12 and OLE end, MG-ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively; QMG response by 56.1% and 71.4%, respectively. Response was observed over multiple consecutive assessments for the vast majority of patients. At Week 130, the least-squares mean (LSM) percentage changes from baseline in MG-ADL score were -61.9% and -47.5% in early and late MG-ADL responders, respectively; the LSM percentage changes from baseline in QMG score were -40.8% and -55.5% in early and late QMG responders, respectively (all p<0.0001). Significant baseline differences between early versus late QMG responders were seen for mean duration of MG (10.46 versus 5.46 years, respectively; p=0.0002) and mean QMG score (18.6 versus 15.1, respectively; p=0.0223).
Conclusion
The findings suggest that although most patients with refractory gMG will achieve clinical response (assessed by MG-ADL or QMG scores) by Week 12 of eculizumab treatment, responses can be observed with longer-term treatment.