Composite end points to assess delay of disability progression by MS treatments.

BACKGROUND: The Expanded Disability Status Scale (EDSS) has low sensitivity and reliability for detecting sustained disability progression (SDP) in multiple sclerosis (MS) trials. OBJECTIVE: This study evaluated composite disability end points as alternatives to EDSS alone. METHODS: SDP rates were determined using 96-week data from the Olympus trial (rituximab in patients with primary progressive MS). SDP was analyzed using composite disability end points: SDP in EDSS, timed 25-foot walk test (T25FWT), or 9-hole peg test (9HPT) (composite A); SDP in T25FWT or 9HPT (composite B); SDP in EDSS and (T25FWT or 9HPT) (composite C); and SDP in any two (EDSS, T25FWT, and 9HPT) (composite D). RESULTS: Overall agreements between EDSS and other disability measures in defining SDP were 66%-73%. Composite A showed similar treatment effect estimate versus EDSS alone with much higher SDP rates. Composite B, C, and D all showed larger treatment effect estimate with different or similar SDP rates versus EDSS alone. Using composite A (24-week confirmation only), B, C, or D could reduce sample sizes needed for MS trials. CONCLUSION: Composite end points including multiple accepted disability measures could be superior to EDSS alone in analyzing disability progression and should be considered in future MS trials.

The CombiRx trial of combined therapy with interferon and glatiramer cetate in relapsing remitting MS: Design and baseline characteristics.

BACKGROUND: Interferon-ß1a (IFNB) and glatiramer acetate (GA) are distinct therapies which are both partially effective for relapsing MS. It is not known if combining the two treatments would be more effective. OBJECTIVE: To review the rationale, design, and baseline characteristics of the CombiRx study of combined treatment with IFNB and GA. METHODS: The key inclusion criteria included a diagnosis of relapsing MS, at least 2 episodes of MS activity in the previous 3 years, expanded disability status scale of 0 to 5.5, and no prior treatment with either IFNB or GA. Subjects were randomized to IFNB+GA, IFNB monotherapy, or GA monotherapy in a 2:1:1 ratio. RESULTS: From 2005 to 2009, we enrolled 1008 subjects. The participants were 72.4% female and 87.6% Caucasian with a mean age of 37.7 years. The median duration of symptoms was 2 years at entry into the study, and the mean EDSS was 2.1. On the baseline MRI, the mean total lesion load was 12.2 ml, and 40% of the participants had enhancing lesions. CONCLUSION: We have recruited a population of patients with clinical and MRI characteristics typical for early MS. The study results will aid in deciding on the optimum early treatment. This trial should serve as a model for future studies of combination therapy.