Efficacy of Ocrelizumab in Patients with Relapsing Multiple Sclerosis: Pooled Analysis of Two Identical Phase III, Double-Blind, Double-Dummy, Interferon Beta-1a-Controlled Studies (S49.003)
Bibliographic record
Abstract
Objective To evaluate the efficacy of ocrelizumab compared with interferon beta-1a (IFNβ-1a) through pooled analysis of efficacy in OPERA I and OPERA II. Background MS pathogenesis is understood to involve two distinct, but overlapping mechanisms, with early inflammation and concurrent or subsequent neurodegeneration. Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20+ B cells, was superior in reducing annualized relapse rate (ARR) vs IFNβ-1a in OPERA I and OPERA II, two identical Phase III, randomized, double-blind, double-dummy trials in relapsing MS. Methods Pooled analyses of OPERA I and OPERA II efficacy were considered to be valid if treatment differences between the ocrelizumab and IFNβ-1a groups for ARR through week 96 and ≥12-week confirmed disability progression (CDP) were broadly consistent between the two studies; i.e. p>0.1 for study-by-treatment group interaction or p≤0.1 for study-by-treatment group interaction and both within-study treatment differences point to the same direction. Pre-specified pooled analyses included ≥12-week and ≥24-week CDP and ≥12-week confirmed disability improvement (CDI) through week 96. Results Consistency of baseline characteristics and treatment effects across both studies met pre-determined criteria for pooled efficacy analysis. Compared with IFNβ-1a, ocrelizumab showed a 47[percnt] reduction in adjusted ARR (p<0.0001) and reduced the risk of 12-week CDP by 40[percnt] (p=0.0006) and 24-week CDP by 40[percnt] (p=0.0025). In pooled analyses, the proportion of ocrelizumab-treated patients that achieved CDI at 12 and 24 weeks was 20.7[percnt] and 15.6[percnt] vs 15.6[percnt] and 11.6[percnt], respectively, for IFNβ-1a-treated patients, representing a 33[percnt] and 36[percnt] relative improvement (relative risk 1.33 [p=0.0194] and 1.36 [p=0.0343]), respectively. Ocrelizumab showed an 18.8[percnt] reduction in brain atrophy vs IFNβ-1a (p=0.0015). Conclusions Pooled analyses of OPERA I and OPERA II efficacy endpoints showed that ocrelizumab significantly suppressed disease progression and increased the proportion of patients with disability improvement over 96 weeks compared with IFNβ-1a. Supported by F. Hoffmann-La Roche
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.031 | 0.024 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.013 | 0.023 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".