Comparison of disease activity in SPMS and PPMS in the context of multicenter clinical trials.
BACKGROUND
Retrospective single center natural history studies have shown that times to reach disability milestones and ages at which they are reached are similar in primary (PPMS) and secondary (SPMS) progressive multiple sclerosis suggesting that they may be phenotypic variations of the same disease.


OBJECTIVE
Here we compared longitudinal disease activity in SPMS and PPMS in the context of international multicenter clinical trials.


METHODS
We analyzed all objective outcome measures that were systematically collected over 2 years for all subjects randomized to placebo arms in one SPMS and one PPMS clinical trial over the last decade. Conventional and exploratory definitions of clinical disease activity were used. Disease activity was analyzed in 3 different categories intermittent activity, progression, and improvement. Conventional MRI measures and one patient reported outcome measure of quality of life were included when available for comparison. Heat maps were drawn for all results followed by hierarchical clustering.


RESULTS
There were 101 outcome variables from 206 SPMS subjects and 79 outcome variables from 135 PPMS subjects. The comparison revealed that SPMS and PPMS subjects exhibited similar disease activity over 2 years in all but two of the variables in common worsening in the EDSS sensory system was more common in PPMS while worsening on the 9 hole PEG was more common in SPMS. Intermittent activity was the most common pattern of disease activity in SPMS and PPMS. Clinical worsening and improvement occurred at similar frequency in both.


CONCLUSIONS
Longitudinal disease activity was nearly identical in SPMS and PPMS subjects in the context of the two multicenter international clinical trials we examined.
MS Clinical Development Group, Biogen Idec, Cambridge, Massachusetts, United States of America.
Rotem
R
Orbach
Zhenming
Z
Zhao
Yong-Cheng
YC
Wang
Gilmore
G
O'Neill
Diego
D
Cadavid
D016000:Cluster Analysis; D018450:Disease Progression; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000503:physiopathology*; D010919:Placebos; D011788:Quality of Life; D013997:Time Factors
D010919:Placebos