期刊
MULTIPLE SCLEROSIS JOURNAL
卷 19, 期 6, 页码 775-781出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458512459685
关键词
Multiple sclerosis; EDSS; rituximab; disability progression; PPMS
资金
- F Hoffmann-La Roche Ltd
- Biogen Idec.
- Roche
- Teva Neuroscience
- Sanofi-Aventis
- Cleveland Clinic
- Daichi-Sankyo
- GlaxoSmithKlein Pharmaceuticals
- Genmab Biopharmaceuticals
- Eli Lilly
- Medivation
- Modigenetech
- Ono Pharmaceuticals
- PTC Therapeutics
- Teva
- Vivus
- University of Pennsylvania
- National Heart, Lung and Blood Institute (NHLBI)
- National Institute of Neurological Disorders and Stroke (NINDS)
- National Multiple Sclerosis Society (NMSS)
- Alexion
- Bayhill
- Bayer
- Novartis
- Consortium of MS Centers
- Genzyme
- Klein-Buendel Incorporated
- Nuron Biotech
- Peptimmune
- Somnus Pharmaceuticals
- Sandoz
- Teva Pharmaceuticals
- UT Southwestern
- Visioneering Technologies Inc.
- National Institutes of Health
- Clayton Foundation for Research
- National Multiple Sclerosis Society
Background: Baseline Expanded Disability Status Scale (EDSS) is usually based on a single measurement. Here we evaluated whether using a baseline EDSS derived from two pre-treatment measurements improves the detection of progression events and the ability to demonstrate a therapeutic effect in delaying MS disability progression. Methods: Real data from OLYMPUS, a phase II/III randomized, placebo-controlled trial of rituximab in patients with primary progressive multiple sclerosis (PPMS), as well as simulated data were analyzed. Several definitions of baseline EDSS were used to capture sustained disability progression (SDP) events. Variations in the EDSS were estimated by linear mixed-effect models. Results: Selecting the higher of two baseline EDSS scores lowered the number of SDP events in both treatment groups, so decreasing sensitivity, and reduced the number of false SDP events, so increasing specificity. Conversely, selecting the lower of two baseline scores increased sensitivity but decreased specificity. Increased power (similar to 7% based on the simulation study) was observed when the average of screening and Week 0 EDSS scores was used for baseline. Conclusion: Baseline EDSS derived from two pre-treatment EDSS measurements may enhance the ability of detecting a therapeutic effect in slowing disability progression in PPMS. This strategy could be implemented in future clinical trials of patients with MS.
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