Contributions
Abstract: P1212
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Fingolimod (FTY) has been shown to reduce clinical and MRI activity in relapsing-remitting patients who switched from interferon (IFN) due to suboptimal treatment response. Assessment of long-term efficacy in this population is an ongoing effort.
Objective: To evaluate the longer-term efficacy of FTY in MS patients who were non-responders to IFNβ-1a treatment over one year in the TRANSFORMS phase 3 trial.
Methods: Patients who received intramuscular IFNβ-1a in the TRANSFORMS core study over 1 year and switched to either 0.5 or 1.25 mg FTY thereafter were classified into responders (R, n=101) and non-responders (NR, n=240). Responders to IFNβ-1a treatment were defined as those patients with none of the following during the core study: confirmed relapses, new/enlarging T2 (neT2) lesions, gadolinium (Gd)-enhancing T1 lesions, or 3-month confirmed disability progression (CDP). Efficacy of fingolimod was evaluated by the annualized relapse rate (ARR, confirmed relapses [defined as ≥0.5 rise on the Expanded Disability Status Scale (EDSS)/1 point on two functional systems (FS) of the EDSS/ 2 points on one of the FS [excluding Bowel/Bladder/Cerebral FS] and unconfirmed relapses [without EDSS confirmation]) up to 96 months (M) of FTY treatment (M0-M96), annualized rate of neT2 lesions during first 36 months of FTY treatment (M0-M36), and estimated by negative binomial regression model.
Results: Median (min, max) exposures to IFNβ-1a and FTY were comparable between the groups; IFNβ-1a: NR 364 [229, 427] vs. R 365 [333, 407] days; FTY: NR 2064 [1, 2826] vs. R 2223 [1, 2833] days. Patients in the NR vs. R group, were younger (Age, mean±SD: 35.6±8.4 vs. 37.3±8.2 years); prior to enrolment in core study, 36% of NR vs 24% of R had 2-3 relapses, and 33% of NR vs. 24% of R had >3 relapses in the previous 1 and 2 years, respectively. In the NR group, post switch to FTY, ARR (95% CI) decreased from 0.74 (0.628; 0.868) during IFNβ-1a treatment to 0.24 (0.201; 0.292) during FTYM0-M96; annualized rate of neT2 lesions (95% CI) also decreased from 3.3 (2.763; 3.846) during IFNβ-1a treatment to 0.81 (0.615; 1.073) during
FTYM0-M36. Corresponding estimates in R group were: ARR, 0.15 (0.107; 0.204) during FTYM0-M96 and annualized rate of neT2 lesions, 0.33 (0.195; 0.554) during FTYM0-M36.
Conclusions: Patients with a suboptimal response to IFNβ-1a in the TRANSFORMS core study had improved long-term efficacy outcomes after switching to FTY.
Disclosure:
Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland
Jeffrey Cohen has received personal compensation for consulting for Genentech, Genzyme, Novartis, and Receptos; as a speaker for Teva; and as Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
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.
Nadia Tenenbaum, Alit Bhatt, Yu Chen are employees of Novartis.
Abstract: P1212
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Fingolimod (FTY) has been shown to reduce clinical and MRI activity in relapsing-remitting patients who switched from interferon (IFN) due to suboptimal treatment response. Assessment of long-term efficacy in this population is an ongoing effort.
Objective: To evaluate the longer-term efficacy of FTY in MS patients who were non-responders to IFNβ-1a treatment over one year in the TRANSFORMS phase 3 trial.
Methods: Patients who received intramuscular IFNβ-1a in the TRANSFORMS core study over 1 year and switched to either 0.5 or 1.25 mg FTY thereafter were classified into responders (R, n=101) and non-responders (NR, n=240). Responders to IFNβ-1a treatment were defined as those patients with none of the following during the core study: confirmed relapses, new/enlarging T2 (neT2) lesions, gadolinium (Gd)-enhancing T1 lesions, or 3-month confirmed disability progression (CDP). Efficacy of fingolimod was evaluated by the annualized relapse rate (ARR, confirmed relapses [defined as ≥0.5 rise on the Expanded Disability Status Scale (EDSS)/1 point on two functional systems (FS) of the EDSS/ 2 points on one of the FS [excluding Bowel/Bladder/Cerebral FS] and unconfirmed relapses [without EDSS confirmation]) up to 96 months (M) of FTY treatment (M0-M96), annualized rate of neT2 lesions during first 36 months of FTY treatment (M0-M36), and estimated by negative binomial regression model.
Results: Median (min, max) exposures to IFNβ-1a and FTY were comparable between the groups; IFNβ-1a: NR 364 [229, 427] vs. R 365 [333, 407] days; FTY: NR 2064 [1, 2826] vs. R 2223 [1, 2833] days. Patients in the NR vs. R group, were younger (Age, mean±SD: 35.6±8.4 vs. 37.3±8.2 years); prior to enrolment in core study, 36% of NR vs 24% of R had 2-3 relapses, and 33% of NR vs. 24% of R had >3 relapses in the previous 1 and 2 years, respectively. In the NR group, post switch to FTY, ARR (95% CI) decreased from 0.74 (0.628; 0.868) during IFNβ-1a treatment to 0.24 (0.201; 0.292) during FTYM0-M96; annualized rate of neT2 lesions (95% CI) also decreased from 3.3 (2.763; 3.846) during IFNβ-1a treatment to 0.81 (0.615; 1.073) during
FTYM0-M36. Corresponding estimates in R group were: ARR, 0.15 (0.107; 0.204) during FTYM0-M96 and annualized rate of neT2 lesions, 0.33 (0.195; 0.554) during FTYM0-M36.
Conclusions: Patients with a suboptimal response to IFNβ-1a in the TRANSFORMS core study had improved long-term efficacy outcomes after switching to FTY.
Disclosure:
Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland
Jeffrey Cohen has received personal compensation for consulting for Genentech, Genzyme, Novartis, and Receptos; as a speaker for Teva; and as Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
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.
Nadia Tenenbaum, Alit Bhatt, Yu Chen are employees of Novartis.