Contributions
Abstract: P913
Type: Poster
Abstract Category: Clinical aspects of MS - 8 Clinical assessment tools
Background: Evidence suggests that the treatment and disease histories of patients with multiple sclerosis may predict long-term clinical outcomes.
Objectives: To assess the ability of variables at baseline and during the first year of the 2-year FREEDOMS and FREEDOMS II phase 3 trials to predict long-term disability outcomes during the trials and their extensions.
Methods: This was a post hoc analysis of pooled data from the fingolimod and placebo groups of the FREEDOMS and FREEDOMS II studies. In the extension phase of each study, patients were switched from placebo to fingolimod. Multiple logistic regression was used to assess which patient or disease characteristics from baseline to month (M) 12 predicted two disability outcome measures (6-month confirmed disability progression [6MCDP] and Expanded Disability Status Scale [EDSS] score >6) during M12‒48. Baseline characteristics included sex, age, duration of MS since diagnosis, previous treatment for MS, number of relapses in the previous 2 years, EDSS score, number of gadolinium-enhancing lesions, T1 hypointense volume and total volume of T2 lesions. Baseline to M12 variables included the number of confirmed relapses, EDSS score change, presence of new T2 lesions and presence of MRI lesion activity.
Results: In total, 1146 and 1875 patients were included in the multiple regression analysis sets for 6MCDP and EDSS outcomes, respectively. Predictors (odds ratio [95% confidence interval]) of 6MCDP were the number of relapses in the 2 years before study baseline (1.286 [1.038-1.592], p=0.0213) and age at baseline (1.030 [1.008-1.053], p=0.0084). EDSS score at baseline (3.310 [2.660-4.120, p< 0.0001]), change in EDSS score from baseline to M12 (2.575 [1.980-3.350], p< 0.0001), and number of relapses between baseline and M12 (1.382 [1.024-1.867], p=0.0346) were all predictors of progression to an EDSS score >6. No single parameter successfully predicted both disability outcomes.
Conclusions: Certain patient and disease characteristics during year 1 of the FREEDOMS trials were predictors of long-term disability outcomes. Previous relapse and age predicted 6MCDP, while EDSS score at baseline or EDSS score worsening and relapses during year 1 were predictive of reaching an EDSS score >6. These findings support early review of treatment regimens to help to prevent worsening disability.
Disclosure:
Pavle Repovic: Acorda Therapeutics, Biogen Idec, EMD Serono, Genzyme, Novartis Pharmaceuticals Corporation, Pfizer and Teva Pharmaceuticals (multiple sources).
Aaron Boster: Acorda Therapeutics, Actelion Pharmaceuticals, Biogen Idec, CNS Therapeutics, Genzyme, Jazz Pharmaceuticals, Medtronic, Novartis Pharmaceuticals, Roche, Serono, Questcor Pharmaceuticals and Teva Pharmaceuticals.
Shannon Ritter, Xiangyi Meng: Novartis Pharmaceuticals Corporation (employees). Davorka Tomic, Daniela Piani Meier: Novartis Pharma AG (employees).
Frederik Barkhof: Biogen Idec, Bayer Schering Pharma, Genzyme, Janssen Alzheimer Immunotherapy, Lundbeck, MediciNova, Merck Serono, Novartis Pharmaceuticals Corporation, Roche, Sanofi-Aventis and Synthon (multiple sources).
Till Sprenger: Actelion, Allergan, ATI Pharma, Biogen Idec, ElectroCore, Novartis, Sanofi Genzyme and Teva.
Abstract: P913
Type: Poster
Abstract Category: Clinical aspects of MS - 8 Clinical assessment tools
Background: Evidence suggests that the treatment and disease histories of patients with multiple sclerosis may predict long-term clinical outcomes.
Objectives: To assess the ability of variables at baseline and during the first year of the 2-year FREEDOMS and FREEDOMS II phase 3 trials to predict long-term disability outcomes during the trials and their extensions.
Methods: This was a post hoc analysis of pooled data from the fingolimod and placebo groups of the FREEDOMS and FREEDOMS II studies. In the extension phase of each study, patients were switched from placebo to fingolimod. Multiple logistic regression was used to assess which patient or disease characteristics from baseline to month (M) 12 predicted two disability outcome measures (6-month confirmed disability progression [6MCDP] and Expanded Disability Status Scale [EDSS] score >6) during M12‒48. Baseline characteristics included sex, age, duration of MS since diagnosis, previous treatment for MS, number of relapses in the previous 2 years, EDSS score, number of gadolinium-enhancing lesions, T1 hypointense volume and total volume of T2 lesions. Baseline to M12 variables included the number of confirmed relapses, EDSS score change, presence of new T2 lesions and presence of MRI lesion activity.
Results: In total, 1146 and 1875 patients were included in the multiple regression analysis sets for 6MCDP and EDSS outcomes, respectively. Predictors (odds ratio [95% confidence interval]) of 6MCDP were the number of relapses in the 2 years before study baseline (1.286 [1.038-1.592], p=0.0213) and age at baseline (1.030 [1.008-1.053], p=0.0084). EDSS score at baseline (3.310 [2.660-4.120, p< 0.0001]), change in EDSS score from baseline to M12 (2.575 [1.980-3.350], p< 0.0001), and number of relapses between baseline and M12 (1.382 [1.024-1.867], p=0.0346) were all predictors of progression to an EDSS score >6. No single parameter successfully predicted both disability outcomes.
Conclusions: Certain patient and disease characteristics during year 1 of the FREEDOMS trials were predictors of long-term disability outcomes. Previous relapse and age predicted 6MCDP, while EDSS score at baseline or EDSS score worsening and relapses during year 1 were predictive of reaching an EDSS score >6. These findings support early review of treatment regimens to help to prevent worsening disability.
Disclosure:
Pavle Repovic: Acorda Therapeutics, Biogen Idec, EMD Serono, Genzyme, Novartis Pharmaceuticals Corporation, Pfizer and Teva Pharmaceuticals (multiple sources).
Aaron Boster: Acorda Therapeutics, Actelion Pharmaceuticals, Biogen Idec, CNS Therapeutics, Genzyme, Jazz Pharmaceuticals, Medtronic, Novartis Pharmaceuticals, Roche, Serono, Questcor Pharmaceuticals and Teva Pharmaceuticals.
Shannon Ritter, Xiangyi Meng: Novartis Pharmaceuticals Corporation (employees). Davorka Tomic, Daniela Piani Meier: Novartis Pharma AG (employees).
Frederik Barkhof: Biogen Idec, Bayer Schering Pharma, Genzyme, Janssen Alzheimer Immunotherapy, Lundbeck, MediciNova, Merck Serono, Novartis Pharmaceuticals Corporation, Roche, Sanofi-Aventis and Synthon (multiple sources).
Till Sprenger: Actelion, Allergan, ATI Pharma, Biogen Idec, ElectroCore, Novartis, Sanofi Genzyme and Teva.