Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial.

Background: The safety and efficacy of ocrelizumab in primary progressive multiple sclerosis were shown in the phase 3 ORATORIO trial. In this study, we assessed the effects of maintaining or switching to ocrelizumab therapy on measures of disease progression and safety in the open-label extension phase of ORATORIO.

Methods: ORATORIO was an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done at 182 study locations including academic centres, hospitals, and community speciality centres within 29 countries across the Americas, Australia, Europe, Israel, New Zealand, and Russia.

Systematic review and network meta-analysis comparing ocrelizumab with other treatments for relapsing multiple sclerosis.

Background: Ocrelizumab was approved for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) by the US Food and Drug Administration in March 2017 and by the European Medicines Agency in January 2018. These approvals were based on two pivotal randomized controlled trials (RCTs), OPERA I and OPERA II, comparing ocrelizumab 600 mg with an active comparator, interferon β-1a 44 μg (Rebif), and the first trial with positive results in patients with PPMS, which compared ocrelizumab with placebo. However, direct evidence of the efficacy and safety of ocrelizumab in RMS compared with other disease-modifying therapies (DMTs) approved for RMS is not available from RCTs.

A simple method for combining binomial counts or proportions with hazard ratios for evidence synthesis of time-to-event data.

In studies with time-to-event data, outcomes may be reported as hazard ratios (HR) or binomial counts/proportions at a specific time point. If the intent is to synthesise evidence by performing a meta-analysis or network meta-analysis (NMA) using the HR as the measure of treatment effect, studies that only report binomial data cannot be included in the network. Methods for converting binomial data to HRs were investigated, so that studies reporting binomial data only could be included in a network of HR data.

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

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 ( = 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).

Accounting for Uncertainty in Decision Analytic Models Using Rank Preserving Structural Failure Time Modeling: Application to Parametric Survival Models.

Objectives: Rank Preserving Structural Failure Time models are one of the most commonly used statistical methods to adjust for treatment switching in oncology clinical trials. The method is often applied in a decision analytic model without appropriately accounting for additional uncertainty when determining the allocation of health care resources. The aim of the study is to describe novel approaches to adequately account for uncertainty when using a Rank Preserving Structural Failure Time model in a decision analytic model.