Subgroup analyses of no evidence of disease activity in patients with relapsing multiple sclerosis who received ocrelizumab or interferon beta-1a in the Phase III OPERA I and OPERA II studies

ObjectiveTo assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS).MethodsBrain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-β-1a (44 μg).ResultsIn patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-β-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-β-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-β-1a within the first 8 weeks.ConclusionEpoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively.Classification of evidenceThis study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.

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

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217318760642 ◽

2018 ◽

Vol 4 (1) ◽

pp. 205521731876064 ◽

Cited By ~ 8

Author(s):

Eva Havrdová ◽

Douglas L Arnold ◽

Amit Bar-Or ◽

Giancarlo Comi ◽

Hans-Peter Hartung ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Interferon Beta ◽

Relative Increase ◽

Disability Progression ◽

T2 Lesions ◽

Superior Efficacy ◽

Intent To Treat ◽

Relapsing Multiple Sclerosis ◽

Treat Population

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.

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Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512450354 ◽

2012 ◽

Vol 18 (11) ◽

pp. 1625-1632 ◽

Cited By ~ 53

Author(s):

Aaron E Miller ◽

Paul O’Connor ◽

Jerry S Wolinsky ◽

Christian Confavreux ◽

Ludwig Kappos ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cox Regression ◽

Statistical Significance ◽

Phase Iii ◽

Lesion Volume ◽

Disability Progression ◽

Positive Effects ◽

Subgroup Analyses ◽

Relapsing Multiple Sclerosis ◽

Interaction Test

Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups. Methods: RMS patients ( n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately. Results: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance. Conclusion: The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.

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