Contributions
Abstract: P1232
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Data from the phase III FREEDOMS, FREEDOMS II and TRANSFORMS trials provide evidence that patients with relapsing-remitting MS (RRMS) benefit from fingolimod (FTY) therapy on all parameters (clinical, radiological, functional). Progression is often reported as an increase in Expanded Disability Status Scale (EDSS) and progression in patients' disease course is usually driven by changes in 1-2 main functional areas (eg, motor, sensory) represented by EDSS.
Objective: Further investigate effect of FTY 0.5 mg/day in patients with RRMS on subscales derived using a factor analysis of EDSS functions.
Methods: PROC FACTOR (SAS) was applied to baseline EDSS data from FREEDOMS, FREEDOMS II and TRANSFORMS, to establish a best fit for the EDSS functions into new subscales. Post hoc analysis of data from FREEDOMS, a 24 month double-blind trial of FTY vs placebo in patients with RRMS was conducted. Treatment effect was assessed by mean change from baseline at 24 months and worsening of units in each subscale identified.
Results: EDSS data from 425 and 418 patients receiving once-daily FTY 0.5 mg or placebo were analysed. Factor analysis of baseline scores generated 2 new subscales. Mean change from baseline at 24 months in EDSS Subscale 1 (functional scale: cerebellar; pyramidal; distance walked without rest or assistance) was significantly improved with FTY vs placebo (0.044 vs 0.345; p< 0.01), but in EDSS Subscale 2 (functional scale: bowel and bladder; brainstem; cerebral; sensory; visual) no significant difference was seen (-0.032 vs 0.096; p=0.08). Treatment effect sizes for mean change at 24 months were 0.178 and 0.072 for Subscales 1 and 2, respectively, vs 0.140 for total EDSS assessed. Significantly fewer patients in FTY group showed a worsening of ≥1 unit (FTY, 45.1% vs placebo, 56.5%; p< 0.01) or ≥2 units (24.1% vs 34.3%; p< 0.01) at any time point in Subscale 1 vs placebo group. In Subscale 2, no significant difference between FTY and placebo was seen in patients with worsening of ≥1 (FTY, 54.9% vs placebo, 57.8%; p=0.41), ≥2 (31.7% vs 35.6%; p=0.24) or ≥3 units (16.3% vs 20.7%; p=0.09).
Conclusions: Significant benefit in change from baseline at Month 24 and proportion of patients with worsening were observed with FTY 0.5 mg/day compared with placebo on EDSS Subscale 1.
Using factor analysis to define novel EDSS subscales may enhance the sensitivity to detect changes in this measure to increase its clinical usefulness, and requires independent validation.
Disclosure:
Gary Cutter has participated in Data and Safety Monitoring Boards: Apotek, Biogen-Idec, Cleveland Clinic (Vivus), GlaxoSmithKline Pharmaceuticals, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Merck/Pfizer, Neuren, Sanofi-Aventis, Teva, Washington University, NHLBI (Protocol Review Committee), NINDS, NICHD (OPRU oversight committee); Consulting or Advisory Boards: Consortium of MS Centers (grant), D3 (Drug Discovery and Development), Genzyme, Genentech, Jansen Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, EMD Serono, Somalution, Teva Pharmaceuticals, Transparency Life Sciences. Dr. Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL.
Florian P Thomas has served as a speaker and/or consultant for Acorda, Biogen Idec, Genzyme, Novartis, and Teva, and has received research support from Biogen Idec and Teva.
Xiangyi Meng and Nadia Tenenbaum are both employees of Novartis Pharmaceuticals Corporation.
Abstract: P1232
Type: Poster
Abstract Category: Therapy - disease modifying - 30 Tools for detecting therapeutic response
Background: Data from the phase III FREEDOMS, FREEDOMS II and TRANSFORMS trials provide evidence that patients with relapsing-remitting MS (RRMS) benefit from fingolimod (FTY) therapy on all parameters (clinical, radiological, functional). Progression is often reported as an increase in Expanded Disability Status Scale (EDSS) and progression in patients' disease course is usually driven by changes in 1-2 main functional areas (eg, motor, sensory) represented by EDSS.
Objective: Further investigate effect of FTY 0.5 mg/day in patients with RRMS on subscales derived using a factor analysis of EDSS functions.
Methods: PROC FACTOR (SAS) was applied to baseline EDSS data from FREEDOMS, FREEDOMS II and TRANSFORMS, to establish a best fit for the EDSS functions into new subscales. Post hoc analysis of data from FREEDOMS, a 24 month double-blind trial of FTY vs placebo in patients with RRMS was conducted. Treatment effect was assessed by mean change from baseline at 24 months and worsening of units in each subscale identified.
Results: EDSS data from 425 and 418 patients receiving once-daily FTY 0.5 mg or placebo were analysed. Factor analysis of baseline scores generated 2 new subscales. Mean change from baseline at 24 months in EDSS Subscale 1 (functional scale: cerebellar; pyramidal; distance walked without rest or assistance) was significantly improved with FTY vs placebo (0.044 vs 0.345; p< 0.01), but in EDSS Subscale 2 (functional scale: bowel and bladder; brainstem; cerebral; sensory; visual) no significant difference was seen (-0.032 vs 0.096; p=0.08). Treatment effect sizes for mean change at 24 months were 0.178 and 0.072 for Subscales 1 and 2, respectively, vs 0.140 for total EDSS assessed. Significantly fewer patients in FTY group showed a worsening of ≥1 unit (FTY, 45.1% vs placebo, 56.5%; p< 0.01) or ≥2 units (24.1% vs 34.3%; p< 0.01) at any time point in Subscale 1 vs placebo group. In Subscale 2, no significant difference between FTY and placebo was seen in patients with worsening of ≥1 (FTY, 54.9% vs placebo, 57.8%; p=0.41), ≥2 (31.7% vs 35.6%; p=0.24) or ≥3 units (16.3% vs 20.7%; p=0.09).
Conclusions: Significant benefit in change from baseline at Month 24 and proportion of patients with worsening were observed with FTY 0.5 mg/day compared with placebo on EDSS Subscale 1.
Using factor analysis to define novel EDSS subscales may enhance the sensitivity to detect changes in this measure to increase its clinical usefulness, and requires independent validation.
Disclosure:
Gary Cutter has participated in Data and Safety Monitoring Boards: Apotek, Biogen-Idec, Cleveland Clinic (Vivus), GlaxoSmithKline Pharmaceuticals, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck/Ono Pharmaceuticals, Merck, Merck/Pfizer, Neuren, Sanofi-Aventis, Teva, Washington University, NHLBI (Protocol Review Committee), NINDS, NICHD (OPRU oversight committee); Consulting or Advisory Boards: Consortium of MS Centers (grant), D3 (Drug Discovery and Development), Genzyme, Genentech, Jansen Pharmaceuticals, Klein-Buendel Incorporated, Medimmune, Novartis, Opexa Therapeutics, Receptos, Roche, EMD Serono, Somalution, Teva Pharmaceuticals, Transparency Life Sciences. Dr. Cutter is employed by the University of Alabama at Birmingham and President of Pythagoras, Inc. a private consulting company located in Birmingham AL.
Florian P Thomas has served as a speaker and/or consultant for Acorda, Biogen Idec, Genzyme, Novartis, and Teva, and has received research support from Biogen Idec and Teva.
Xiangyi Meng and Nadia Tenenbaum are both employees of Novartis Pharmaceuticals Corporation.