MRI metrics as surrogate endpoints for EDSS progression in SPMS patients treated with IFN beta-1b.
BACKGROUND
Although metrics derived from conventional MRI (cMRI) are widely used as outcome measures in clinical trials of MS, no formal study has been performed to validate cMRI metrics as surrogate endpoints for disability progression in MS.


METHODS
A validation procedure was applied to the clinical and MRI data collected in the context of the European randomized, double-blind, placebo-controlled trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive MS. The Prentice operational criteria were used to assess surrogacy for the number of active lesions seen on the first year T2-weighted MRI scans and the percentage T2 lesion volume change between the baseline and the first year MRI scans. The primary clinical outcome was disability at study exit (3 years), adjusted for the baseline disability.


RESULTS
The number of active T2 lesions and the T2 lesion volume percentage change over the first year of the study accounted for 57% of the treatment effect on disability progression over the entire study duration. On the contrary, the same cMRI metrics accounted for 79% of the treatment effect on the relapse rate.


CONCLUSIONS
This study shows that the beneficial effect of IFNbeta-1b on disability accumulation in patients with secondary progressive MS is, to a large extent, independent of the changes detected using cMRI. As a consequence, cMRI metrics should not be used as a stand-alone measure of outcome in phase III trials of IFNbeta in secondary progressive MS.
Unit of Clinical Epidemiology and Trials, National Institute for Cancer Research, Genoa, Italy.
M P
MP
Sormani
P
P
Bruzzi
K
K
Beckmann
K
K
Wagner
D H
DH
Miller
L
L
Kappos
M
M
Filippi
D015415:Biomarkers; D001921:Brain / Q000473:pathology*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000706:statistics & numerical data; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000473:pathology; D012044:Regression Analysis; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015415:Biomarkers; D007155:Immunologic Factors; D000068576:Interferon beta-1b; D016899:Interferon-beta