No evidence of disease activity (NEDA) analysis by epochs in patients with relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a

Eva Havrdová, Douglas L Arnold, Amit Bar-Or, Giancarlo Comi, Hans-Peter Hartung, Ludwig Kappos, Fred Lublin, Krzysztof Selmaj, Anthony Traboulsee, Shibeshih Belachew, Iain Bennett, Regine Buffels, Hideki Garren, Jian Han, Laura Julian, Julie Napieralski, Stephen L Hauser, Gavin Giovannoni, Eva Havrdová, Douglas L Arnold, Amit Bar-Or, Giancarlo Comi, Hans-Peter Hartung, Ludwig Kappos, Fred Lublin, Krzysztof Selmaj, Anthony Traboulsee, Shibeshih Belachew, Iain Bennett, Regine Buffels, Hideki Garren, Jian Han, Laura Julian, Julie Napieralski, Stephen L Hauser, Gavin Giovannoni

Abstract

Background: No evidence of disease activity (NEDA; defined as no 12-week confirmed disability progression, no protocol-defined relapses, no new/enlarging T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry baseline is commonly used as a treatment outcome in multiple sclerosis (MS).

Objective: The objective of this paper is to assess the effect of ocrelizumab on NEDA using re-baselining analysis, and the predictive value of NEDA status.

Methods: NEDA was assessed in a modified intent-to-treat population (n = 1520) from the pooled OPERA I and OPERA II studies over various epochs in patients with relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN β-1a; 44 μg).

Results: NEDA was increased with ocrelizumab vs IFN β-1a over 96 weeks by 75% (p < 0.001), from Week 0‒24 by 33% (p < 0.001) and from Week 24‒96 by 72% (p < 0.001). Among patients with disease activity during Weeks 0‒24, 66.4% vs 24.3% achieved NEDA during Weeks 24‒96 in the ocrelizumab and IFN β-1a groups (relative increase: 177%; p < 0.001).

Conclusion: Superior efficacy with ocrelizumab compared with IFN β-1a was consistently seen in maintaining NEDA status in all epochs evaluated. By contrast with IFN β-1a, the majority of patients with disease activity early in the study subsequently attained NEDA status with ocrelizumab.

Keywords: MRI activity; NEDA; disability progression; disease activity; relapse.

Figures

Figure 1.
Figure 1.
Proportion of patients with NEDA during (a) Weeks 0–96, and (b) during Weeks 24–96, re-baselined to Week 24. Compared using the Cochran–Mantel–Haenszel test stratified by study, geographic region (United States vs rest of world) and baseline EDSS score (

Figure 2.

Proportion of patients with NEDA…

Figure 2.

Proportion of patients with NEDA during (a) Weeks 24–96, (b) Weeks 24–48 among…

Figure 2.
Proportion of patients with NEDA during (a) Weeks 24–96, (b) Weeks 24–48 among patients with EDA in Weeks 0–24 and (c) Weeks 48–96 among patients with EDA in Weeks 24–48. All components of NEDA including 12-week CDP are defined relative to Week 24 (a) and (b), and relative to Week 48 (c). Comparison using the Cochran–Mantel–Haenszel test stratified by study, geographic region (United States vs rest of world) and baseline EDSS score (
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Figure 2.
Figure 2.
Proportion of patients with NEDA during (a) Weeks 24–96, (b) Weeks 24–48 among patients with EDA in Weeks 0–24 and (c) Weeks 48–96 among patients with EDA in Weeks 24–48. All components of NEDA including 12-week CDP are defined relative to Week 24 (a) and (b), and relative to Week 48 (c). Comparison using the Cochran–Mantel–Haenszel test stratified by study, geographic region (United States vs rest of world) and baseline EDSS score (

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