Abstract: P1227
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Multiple Sclerosis Severity Score (MSSS) is a method of assessing disease severity over time based on expanded disability status scale (EDSS) scores and accounting for disease duration (Roxburgh et al Neurology 2005; Pachner et al J Neurol Sci. 2009).
Objective: To assess the effect of fingolimod on MSSS in patients with relapsing MS.
Methods: This post hoc analysis used pooled data from FREEDOMS and FREEDOMS II (fingolimod 0.5 mg vs placebo, n=1556) core studies (24 month [M]) and their extensions and from TRANSFORMS (fingolimod 0.5 mg vs intramuscular interferon beta-1a [IFN-β], n=860) core trial (12M) and its extension. MSSS was assessed during core study and up to M48 (TRANSFORMS extension, n=509) and M96 (FREEDOMS/FREEDOMS II extension, n=251). During the core periods, change in MSSS from baseline (BL) to M24 (for the pooled FREEDOMS studies) and from BL to M12 (TRANSFORMS study) was analysed with ANCOVA models adjusted for treatment, age and BL MSSS. We present least squares (LS) means and p values of these models, and summary means of MSSS for core and the extension phases.
Results: In the pooled FREEDOMS and FREEDOMS II core studies, improvement in MSSS from BL to M24 was significantly higher in fingolimod vs placebo group (-0.53 vs -0.37; p=0.0385). Over 96 M, fingolimod had sustained benefit on MSSS in patients continuing the therapy (BL: 3.56, M24: 3.03, M48: 2.74, M96: 2.28). MSSS also improved in patients switching from placebo to fingolimod at 24 M (BL: 3.68, M24: 3.27, M48: 2.93, M96: 2.26). In the TRANSFORMS study, the change in MSSS from BL to M12 was significantly lower in fingolimod vs IFN-β group (-0.433 vs -0.224, p=0.0216). Over 48 M, fingolimod had sustained beneficial effect on MSSS in patients continuing the therapy (BL: 3.71, M12: 3.25, M24: 3.19, M48: 2.76). The MSSS was improved in the group of patients who switched from IFN-β to fingolimod after the core phase at M12 (BL: 3.68, M12: 3.43, M24: 3.15, M48: 2.74).
Conclusions: The MSSS improved significantly in fingolimod-treated patients not only vs placebo- but also vs IFN-β-treated patients. An improvement was also seen in placebo and IFN-β patients, and after switching to fingolimod during the extension. Continuous fingolimod therapy maintained its beneficial effect over 96 months. These findings suggest that fingolimod has a favourable and sustained impact on MS severity over the long-term.
Disclosure: This study is supported by Novartis Pharma AG, Basel, Switzerland.
Xavier Montalban has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, and Teva Pharmaceuticals.
Anthony T Reder has received compensation for serving as consultants or speakers, or received research support from Bayer, Biogen Idec, BioMS Medical Corp, Genentech, Genzyme, Novartis, Serono, Questcor.
Jeffrey Cohen has received personal compensation from Biogen Idec, Lilly, and Novartis for consulting services and financial support for research activities from Biogen Idec, Genzyme, Novartis, Serono and Teva.
Ludwig Kappos" institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Biogen Idec, CLC Behring, Genentech, GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Praxicon, Roche, Sanofi-Aventis, Santhera, Siemens and Teva. Prof Kappos has received grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis and Roche Research foundations.
Davorka Tomic, Daniela Piani Meier and Shannon Ritter are employees of Novartis.
Abstract: P1227
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Multiple Sclerosis Severity Score (MSSS) is a method of assessing disease severity over time based on expanded disability status scale (EDSS) scores and accounting for disease duration (Roxburgh et al Neurology 2005; Pachner et al J Neurol Sci. 2009).
Objective: To assess the effect of fingolimod on MSSS in patients with relapsing MS.
Methods: This post hoc analysis used pooled data from FREEDOMS and FREEDOMS II (fingolimod 0.5 mg vs placebo, n=1556) core studies (24 month [M]) and their extensions and from TRANSFORMS (fingolimod 0.5 mg vs intramuscular interferon beta-1a [IFN-β], n=860) core trial (12M) and its extension. MSSS was assessed during core study and up to M48 (TRANSFORMS extension, n=509) and M96 (FREEDOMS/FREEDOMS II extension, n=251). During the core periods, change in MSSS from baseline (BL) to M24 (for the pooled FREEDOMS studies) and from BL to M12 (TRANSFORMS study) was analysed with ANCOVA models adjusted for treatment, age and BL MSSS. We present least squares (LS) means and p values of these models, and summary means of MSSS for core and the extension phases.
Results: In the pooled FREEDOMS and FREEDOMS II core studies, improvement in MSSS from BL to M24 was significantly higher in fingolimod vs placebo group (-0.53 vs -0.37; p=0.0385). Over 96 M, fingolimod had sustained benefit on MSSS in patients continuing the therapy (BL: 3.56, M24: 3.03, M48: 2.74, M96: 2.28). MSSS also improved in patients switching from placebo to fingolimod at 24 M (BL: 3.68, M24: 3.27, M48: 2.93, M96: 2.26). In the TRANSFORMS study, the change in MSSS from BL to M12 was significantly lower in fingolimod vs IFN-β group (-0.433 vs -0.224, p=0.0216). Over 48 M, fingolimod had sustained beneficial effect on MSSS in patients continuing the therapy (BL: 3.71, M12: 3.25, M24: 3.19, M48: 2.76). The MSSS was improved in the group of patients who switched from IFN-β to fingolimod after the core phase at M12 (BL: 3.68, M12: 3.43, M24: 3.15, M48: 2.74).
Conclusions: The MSSS improved significantly in fingolimod-treated patients not only vs placebo- but also vs IFN-β-treated patients. An improvement was also seen in placebo and IFN-β patients, and after switching to fingolimod during the extension. Continuous fingolimod therapy maintained its beneficial effect over 96 months. These findings suggest that fingolimod has a favourable and sustained impact on MS severity over the long-term.
Disclosure: This study is supported by Novartis Pharma AG, Basel, Switzerland.
Xavier Montalban has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, and Teva Pharmaceuticals.
Anthony T Reder has received compensation for serving as consultants or speakers, or received research support from Bayer, Biogen Idec, BioMS Medical Corp, Genentech, Genzyme, Novartis, Serono, Questcor.
Jeffrey Cohen has received personal compensation from Biogen Idec, Lilly, and Novartis for consulting services and financial support for research activities from Biogen Idec, Genzyme, Novartis, Serono and Teva.
Ludwig Kappos" institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Biogen Idec, CLC Behring, Genentech, GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Praxicon, Roche, Sanofi-Aventis, Santhera, Siemens and Teva. Prof Kappos has received grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, and the Novartis and Roche Research foundations.
Davorka Tomic, Daniela Piani Meier and Shannon Ritter are employees of Novartis.