Contributions
Abstract: P672
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background Sustained improvement in disability status is an emerging goal of therapy for MS. Disability improvement has been described with high-efficacy therapies and has been used as a secondary outcome in recent MS clinical trials. Definitions of confirmed disability improvement (CDI) have varied in these trials.
Objective To evaluate the proportion of patients with CDI over time while on long-term (up to 8 years) fingolimod treatment in the Phase 3 TRANSFORMS trial and its extensions.
Methods The analysis included patients who had an Expanded Disability Status Scale (EDSS) score ≥2.0 at baseline and were randomised to fingolimod 1.25mg (N=244), fingolimod 0.5mg (the fingolimod-0.5 cohort; N=247), or interferon beta-1a (the IFN-to-fingolimod-switch cohort; N=254) during the 12-month core phase of TRANSFORMS. All patients received fingolimod 0.5mg during trial extensions. Confirmed disability improvement (CDI) was defined as a confirmed ≥1 or ≥0.5 point decrease in EDSS score in patients with baseline scores ≤5.0 or ≥5.5, respectively; CDI plus was defined as a ≥20% improvement in score on the 9-hole peg test (9HPT), a ≥20% improvement in the timed 25-foot walking test (T25FWT), or a ≥1 decrease in EDSS score lasting ≥166 days. This study was not designed to determine whether selective patient drop-out or differences in CDI definition had significant impact on outcomes.
Results The analysis included a total of 745 patients. Mean (SD) scores for EDSS, 9HPT, and T25FWT were 3.04 (1.01), 24.1 (12.4), and 7.85 (10.43), respectively. A total of 328 patients were observed for 96 months (completers). Completers and non-completers had similar baseline characteristics, apart from 9HPT (23.3 vs 24.7, respectively; p=0.005) and T25FWT (7.58 vs 8.06, respectively; p=0.021). At Month 96, KM estimates (95% CI) for cumulative probability of having CDI were 36.9% (30.0, 44.8) and 35.1% (28.2, 43.1) in the fingolimod-0.5 and IFN-to-fingolimod-switch cohorts, respectively. When using the CDI plus definition to take into account disability measures other than EDSS, the KM estimates were 52.0% (44.4, 60.0) and 48.3% (40.6, 56.6), respectively.
Conclusions In patients with RRMS enrolled in the active-comparator study TRANSFORMS and followed for up to 8 years, 35-52% experienced confirmed improvements in their disability while on fingolimod. Numerically higher improvement rates were observed when the CDI definition included 9HPT or T25FWT along with EDSS.
Disclosure: Funding statement: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Bruce Cree has received personal compensation for consulting from Abbvie, Biogen Idec, EMD Serono and Novartis.
Jeffrey Cohen reports personal compensation for consulting for Adamas, Merck, Mallinckrodt, Novartis, and Receptos and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical
Diego Silva, Shannon Ritter, Daniela Piani Meier, Davorka Tomic and David Leppert are employees of Novartis
Ludwig Kappos has received no personal compensation. LK´s institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera,Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Abstract: P672
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background Sustained improvement in disability status is an emerging goal of therapy for MS. Disability improvement has been described with high-efficacy therapies and has been used as a secondary outcome in recent MS clinical trials. Definitions of confirmed disability improvement (CDI) have varied in these trials.
Objective To evaluate the proportion of patients with CDI over time while on long-term (up to 8 years) fingolimod treatment in the Phase 3 TRANSFORMS trial and its extensions.
Methods The analysis included patients who had an Expanded Disability Status Scale (EDSS) score ≥2.0 at baseline and were randomised to fingolimod 1.25mg (N=244), fingolimod 0.5mg (the fingolimod-0.5 cohort; N=247), or interferon beta-1a (the IFN-to-fingolimod-switch cohort; N=254) during the 12-month core phase of TRANSFORMS. All patients received fingolimod 0.5mg during trial extensions. Confirmed disability improvement (CDI) was defined as a confirmed ≥1 or ≥0.5 point decrease in EDSS score in patients with baseline scores ≤5.0 or ≥5.5, respectively; CDI plus was defined as a ≥20% improvement in score on the 9-hole peg test (9HPT), a ≥20% improvement in the timed 25-foot walking test (T25FWT), or a ≥1 decrease in EDSS score lasting ≥166 days. This study was not designed to determine whether selective patient drop-out or differences in CDI definition had significant impact on outcomes.
Results The analysis included a total of 745 patients. Mean (SD) scores for EDSS, 9HPT, and T25FWT were 3.04 (1.01), 24.1 (12.4), and 7.85 (10.43), respectively. A total of 328 patients were observed for 96 months (completers). Completers and non-completers had similar baseline characteristics, apart from 9HPT (23.3 vs 24.7, respectively; p=0.005) and T25FWT (7.58 vs 8.06, respectively; p=0.021). At Month 96, KM estimates (95% CI) for cumulative probability of having CDI were 36.9% (30.0, 44.8) and 35.1% (28.2, 43.1) in the fingolimod-0.5 and IFN-to-fingolimod-switch cohorts, respectively. When using the CDI plus definition to take into account disability measures other than EDSS, the KM estimates were 52.0% (44.4, 60.0) and 48.3% (40.6, 56.6), respectively.
Conclusions In patients with RRMS enrolled in the active-comparator study TRANSFORMS and followed for up to 8 years, 35-52% experienced confirmed improvements in their disability while on fingolimod. Numerically higher improvement rates were observed when the CDI definition included 9HPT or T25FWT along with EDSS.
Disclosure: Funding statement: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Bruce Cree has received personal compensation for consulting from Abbvie, Biogen Idec, EMD Serono and Novartis.
Jeffrey Cohen reports personal compensation for consulting for Adamas, Merck, Mallinckrodt, Novartis, and Receptos and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical
Diego Silva, Shannon Ritter, Daniela Piani Meier, Davorka Tomic and David Leppert are employees of Novartis
Ludwig Kappos has received no personal compensation. LK´s institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: Steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera,Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; license fees for Neurostatus products; and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.