title: Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation.
abstract: Despite prolonged survival, patients with multiple sclerosis (MS) experience considerable morbidity, which adversely impacts quality of life. To assess the risk-benefit of a clinical trial of high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation for MS, we sought to determine the natural history of the disease in a comparison group of untreated patients. We identified 285 individuals with 2132 combined observation years (median: 5.6 years; 5th to 95th percentile: 1-21 years), with Expanded Disability Status Scale (EDSS) scores of 3.0-5.5 at baseline observation. Disease-related mortality was zero at five years, 5.4% at 10 years, and 22% at 15 years (40 patients contributing to the data point; 95% confidence interval: 4-32%). Risk for progression to advanced disability, defined as an EDSS score of 8, was very low for the subgroup with a baseline EDSS score of 3-3.5; however, for those with a baseline EDSS score of 4-5.5, 3% had advanced disability after two years, 5% after three years, 6% after four years, 12% after five years, and 40% after 10 years. The estimated probability of disease progression, defined as an increase in EDSS score by > or = 1.0 sustained for at least 180 days, was 5% after one year, 14% after two years, 22% after three years, 38% after five years, 57% after 10 years, and >80% after 20 years of observation. The relevance of these features to the design of the clinical trial is discussed.
authors.affiliation: Sylvia Lawry Centre for Multiple Sclerosis Research, Munich, Germany. daumer@slcmsr.org
authors.forename: M
authors.initials: M
authors.lastname: Daumer
authors.forename: L M
authors.initials: LM
authors.lastname: Griffith
authors.forename: W
authors.initials: W
authors.lastname: Meister
authors.forename: R A
authors.initials: RA
authors.lastname: Nash
authors.forename: J S
authors.initials: JS
authors.lastname: Wolinsky
mesh_terms: D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016208:Databases, Factual; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012107:Research Design; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D007166:Immunosuppressive Agents