OBJECTIVE: In multiple sclerosis (MS), the aim of therapies is to prevent the accumulation of irreversible disability. This is difficult to assess given the short time course of clinical trials. MRI markers and relapses are often used as surrogate of disability in MS studies, but their validity remains controversial. We sought to validate, at the individual patient level, MRI lesions and relapses as surrogates for disability progression over the course of MS trials. METHODS: Individual patient data from a large, placebo-controlled trial of interferon β-1a in relapsing-remitting MS (RRMS) were analyzed. The Prentice criteria were applied to evaluate surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]) over the 2-year follow-up. RESULTS: All Prentice criteria were satisfied. Treatment reduced by 31% the odds of having EDSS worsening over 2 years, reducing the mean number of MRI lesions by 61% and the mean number of relapses by 36% over 1 year. Both 1-year MRI lesion activity and relapses, when considered independently, accounted for more than 60% of the treatment effect on 2-year EDSS worsening. A combination of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on EDSS worsening over 2 years. CONCLUSIONS: A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the corresponding effect on 2-year EDSS worsening. This short-term combined measure appears to be a surrogate for disability progression over a longer term when evaluating the effect of interferon in RRMS.
OBJECTIVE: In multiple sclerosis (MS), the aim of therapies is to prevent the accumulation of irreversible disability. This is difficult to assess given the short time course of clinical trials. MRI markers and relapses are often used as surrogate of disability in MS studies, but their validity remains controversial. We sought to validate, at the individual patient level, MRI lesions and relapses as surrogates for disability progression over the course of MS trials. METHODS: Individual patient data from a large, placebo-controlled trial of interferon β-1a in relapsing-remitting MS (RRMS) were analyzed. The Prentice criteria were applied to evaluate surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]) over the 2-year follow-up. RESULTS: All Prentice criteria were satisfied. Treatment reduced by 31% the odds of having EDSS worsening over 2 years, reducing the mean number of MRI lesions by 61% and the mean number of relapses by 36% over 1 year. Both 1-year MRI lesion activity and relapses, when considered independently, accounted for more than 60% of the treatment effect on 2-year EDSS worsening. A combination of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on EDSS worsening over 2 years. CONCLUSIONS: A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the corresponding effect on 2-year EDSS worsening. This short-term combined measure appears to be a surrogate for disability progression over a longer term when evaluating the effect of interferon in RRMS.
Authors: Cather M Cala; Carson E Moseley; Chad Steele; Sarah M Dowdy; Gary R Cutter; Jayne M Ness; Tara M DeSilva Journal: J Neuroimmunol Date: 2016-04-30 Impact factor: 3.478
Authors: Stuart D Cook; Suhayl Dhib-Jalbut; Peter Dowling; Luca Durelli; Corey Ford; Gavin Giovannoni; June Halper; Colleen Harris; Joseph Herbert; David Li; John A Lincoln; Robert Lisak; Fred D Lublin; Claudia F Lucchinetti; Wayne Moore; Robert T Naismith; Carlos Oehninger; Jack Simon; Maria Pia Sormani Journal: Int J MS Care Date: 2012
Authors: Claudio Gasperini; Luca Prosperini; Mar Tintoré; Maria Pia Sormani; Massimo Filippi; Jordi Rio; Jacqueline Palace; Maria A Rocca; Olga Ciccarelli; Frederik Barkhof; Jaume Sastre-Garriga; Hugo Vrenken; Jette L Frederiksen; Tarek A Yousry; Christian Enzinger; Alex Rovira; Ludwig Kappos; Carlo Pozzilli; Xavier Montalban; Nicola De Stefano Journal: Neurology Date: 2018-12-26 Impact factor: 9.910
Authors: Carmen Tur; Marcello Moccia; Frederik Barkhof; Jeremy Chataway; Jaume Sastre-Garriga; Alan J Thompson; Olga Ciccarelli Journal: Nat Rev Neurol Date: 2018-01-12 Impact factor: 42.937
Authors: Ilana R Leppert; S Narayanan; D Araújo; P S Giacomini; Y Lapierre; D L Arnold; G B Pike Journal: J Neurol Date: 2014-02-26 Impact factor: 4.849