Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments.

Background: Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) ß-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives: To compare the treatment effect of OCR vs six DMTs' (IFN ß-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. Methods: Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. Results: The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts. Conclusion: OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS. Registration: OPERA I (NCT01247324), OPERA II (NCT01412333).

Implementation of a data control framework to ensure confidentiality, integrity, and availability of high-quality real-world data (RWD) in the NeuroTransData (NTD) registry.

Objective: To implement a dynamic data management and control framework that meets the multiple demands of high data quality, rigorous information technology security, and flexibility to continuously incorporate new methodology for a large disease registry. Materials and Methods: Guided by relevant sections of the COBIT framework and ISO 27001 standard, we created a data control framework supporting high-quality real-world data (RWD) studies in multiple disease areas. We first mapped and described the entire data journey and identified potential risks for data loss or inconsistencies. Based on this map, we implemented a control framework adhering to best practices and tested its effectiveness through an analysis of random data samples. An internal strategy board was set up to regularly identify and implement potential improvements. Results: We herein describe the implementation of a data management and control framework for multiple sclerosis, one disease area in the NeuroTransData (NTD) registry that exemplifies the dynamic needs for high-quality RWD analysis. Regular manual and automated analysis of random data samples at multiple checkpoints guided the development and implementation of the framework and continue to ensure timely identification of potential threats to data accuracy. Discussion and conclusions: High-quality RWD, especially those derived from long-term disease registries, are of increasing importance from regulatory and reimbursement perspectives, requiring owners to provide data of comparable quality to clinical trials. The framework presented herein responds to the call for transparency in real-world analyses and allows doctors and patients to experience an immediate benefit of the collected data for individualized optimal care.

Development of Registry Data to Create Interactive Doctor-Patient Platforms for Personalized Patient Care, Taking the Example of the DESTINY System.

"Real-world evidence (RWE)" is becoming increasingly important in order to integrate the results of randomized studies into everyday clinical practice. The data collection of RWE is usually derived from large-scale national and international registries, often driven by academic centers. We have developed a digitalized doctor-patient platform called DESTINY (DatabasE-assiSted Therapy decIsioN support sYstem) that is utilized by NeuroTransData (NTD), a network of neurologists and psychiatrists throughout Germany. This platform can be integrated into everyday practice and, as well as being used for scientific evaluations in healthcare research, can also serve as an individual, personalized treatment application. Its various modules allow for a timely identification of side-effects or interactions of treatments, can involve patients via the "My NTC Health Guide" portal, and can collect data of individual disease histories that are integrated into innovative algorithms, e.g., for the prediction of treatment response [currently available for multiple sclerosis (MS), with other indications in the pipeline]. Here, we describe the doctor-patient platform DESTINY for outpatient neurological practices and its contribution to improved treatment success as well as reduction of healthcare costs. Platforms like DESTINY may facilitate the goal of personalized healthcare.

Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry.

BACKGROUND: Comparative effectiveness (CE) research allows real-world treatment comparisons using outcome measurements important to physicians/patients. This German NeuroTransData registry-based analysis compared delayed-release dimethyl fumarate (DMF) effectiveness with interferons (IFN), glatiramer acetate (GA), teriflunomide (TERI), or fingolimod (FTY) in patients with relapsing-remitting multiple sclerosis (RRMS) using propensity score matching (PSM). METHODS: Data from registry patients aged ≥ 18 years with RRMS, ≥ 1 relapse, and Expanded Disability Status Scale (EDSS) assessment(s) after index therapy initiation underwent 1:1 PSM to match DMF with comparator populations baseline characteristics. Primary outcome measurement was time to first relapse (TTFR). Secondary outcome measurements included annualised relapse rate (ARR), proportion of patients relapse free at 12 and 24 months, time to index therapy discontinuation (TTD), and reasons for discontinuation. Exploratory analyses included time to 3- and 6-month EDSS confirmed disability progression (CDP). Non-pairwise censoring was the primary analysis method; pairwise censoring was the main sensitivity analysis method. FINDINGS: Post-matched cohorts were well-balanced. By non-pairwise censoring, TTFR and ARR were significantly lower in DMF populations versus matched IFN, GA, and TERI, but there was no evidence of difference between DMF and FTY. TTD was similar between DMF and IFN, GA, and TERI, but significantly shorter versus FTY. Time to CDP generally showed no evidence of difference between DMF and comparator populations. Pairwise censored analysis results confirmed the non-pairwise censoring results. INTERPRETATION: These results support previous CE studies in demonstrating relative improvement in real-world effectiveness with DMF versus first-line agents IFN, GA, and TERI, and similar effectiveness versus FTY.