Abstract: P1283
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: Fingolimod, an oral sphingosine 1-phosphate receptor modulator that showed significant benefits in suppressing disease activity and slowing disease progression in relapsing multiple sclerosis (RMS), was evaluated for primary progressive MS (PPMS) in the INFORMS study. In the overall study population there was no effect of fingolimod on disease progression, in spite of a significant reduction in inflammatory MRI activity. However, the level of inflammatory activity in INFORMS was very low, with 13% of patients having Gd+ lesions at baseline, and 6% relapsing during the study.
Objective: To assess the potential benefit of fingolimod 0.5 mg on disease progression in PPMS patients with inflammatory activity, including the subgroup of younger patients.
Methods: Time to 3-month confirmed disability progression was assessed in patients with one or more Gd+ lesion at baseline (Gd+ patients) (n=107) vs those without Gd+ lesion at baseline (Gd- patients) (n=713), based on the composite endpoint of change from baseline in Expanded Disability Status Scale (EDSS), 25-Foot Timed-Walk Test or 9-Hole Peg Test. A key secondary endpoint was disability progression as assessed by EDSS. Subgroups of Gd+ patients ≤ 50 years (n=76) vs Gd-patients >50 years (n=311), and of relapsing (n=47) vs non-relapsing (n=776) patients were also analysed. A Cox regression model was used to estimate treatment effect vs placebo.
Results: Risk reduction [RR] for disease progression compared to placebo was 7.10% (p=0.750) and 2.65% (p=0.770) in Gd+ and Gd- patients, respectively, for the composite endpoint, and 25.31% (p=0.274) and 6.91% (p=0.523) by EDSS. RR was 8.48% (p=0.739) and -9.45% (p=0.517) in Gd+ patients ≤50 and Gd- patients >50, respectively, for the composite endpoint, and 36.15% (p=0.145) and -6.68% (p=0.712) by EDSS. A weak trend for RR was also observed in the subgroup of relapsing patients for EDSS [relapsing: 19.50% (p=0.725); non-relapsing: 9.06% (p=0.370)].
Conclusion: The effects of fingolimod in this post hoc subgroup analysis indicate a possibility of a treatment effect in younger patients with Gd+ lesions or relapses, which can only be validated in a further trial, more focused on such patients. This observation is consistent with other studies in PPMS and suggests that in a subgroup of PPMS patients controlling for inflammatory disease activity may have some impact on progression.
Disclosure: Fred Lublin has received compensation for service on steering committees, data monitoring boards or as a consultant for Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi; Acorda; Questcor/Malinckrodt; Roche, Genentech; Celgene; Genzyme, MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; BBB technologies; Akros and is CoChief Editor of Multiple Sclerosis and Related Diseases.Mark S Freedman has received compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi‐Aventis, and Teva Canada Innovation.Bruce A C Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Genzyme Sanofi, MedImmune, Novartis, Shire and Teva.Jerry S Wolinsky has received compensation for service on steering committees, data monitoring boards or as a consultant for AbbVie, Acetilon, Alkermes, Athersys, Inc., EMD Serono, Forward Pharma, Genentech, Genzyme, Novartis, Roche, Teva, toBBB and XenoPort. He has received research support from Genzyme, Sanofi, the National Institutes of Health and the National Multiple Sclerosis Society and royalties for monoclonal antibodies outlicensed to Chemicon International through the University of Texas Health Science Center at Houston.Howard L Weiner has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, and Teva Neuroscience as a consultant, speaker, or scientific advisory board member.Catherine Lubetzki has received personal compensation for activities with BiogenIdec, Novartis, Genzyme, Roche, Vertex.Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia from Bayer, Biogen, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Octapharma, opexa, Roche, Teva , Sanofi with approval by the Rector of HeinrichHeineUniversity.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.Bernard MJ Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Pharmaceuticals, Genzyme and Roche as a consultant and as a scientific advisory board member.Ludwig Kappos´s institution has received in the last 3 years and used exclusively for research support: steering committee, advisory board, consultancy or speaker fees, or support of educational activities from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, and CSL Behring; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.David H Miller has received compensation for consulting from Biogen Idec, Novartis, GlaxoSmithKline, Bayer Schering Pharma, Genzyme, and Mitsubishi Pharma Europe and grants for central MRI analysis in MS trials from Novartis, Biogen Idec, Apitope and GlaxoSmithKline.Martin Merschhemke, Bingbing Li, Norman Putzki, and Dieter A Häring are employees of Novartis.
Abstract: P1283
Type: Poster
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Background: Fingolimod, an oral sphingosine 1-phosphate receptor modulator that showed significant benefits in suppressing disease activity and slowing disease progression in relapsing multiple sclerosis (RMS), was evaluated for primary progressive MS (PPMS) in the INFORMS study. In the overall study population there was no effect of fingolimod on disease progression, in spite of a significant reduction in inflammatory MRI activity. However, the level of inflammatory activity in INFORMS was very low, with 13% of patients having Gd+ lesions at baseline, and 6% relapsing during the study.
Objective: To assess the potential benefit of fingolimod 0.5 mg on disease progression in PPMS patients with inflammatory activity, including the subgroup of younger patients.
Methods: Time to 3-month confirmed disability progression was assessed in patients with one or more Gd+ lesion at baseline (Gd+ patients) (n=107) vs those without Gd+ lesion at baseline (Gd- patients) (n=713), based on the composite endpoint of change from baseline in Expanded Disability Status Scale (EDSS), 25-Foot Timed-Walk Test or 9-Hole Peg Test. A key secondary endpoint was disability progression as assessed by EDSS. Subgroups of Gd+ patients ≤ 50 years (n=76) vs Gd-patients >50 years (n=311), and of relapsing (n=47) vs non-relapsing (n=776) patients were also analysed. A Cox regression model was used to estimate treatment effect vs placebo.
Results: Risk reduction [RR] for disease progression compared to placebo was 7.10% (p=0.750) and 2.65% (p=0.770) in Gd+ and Gd- patients, respectively, for the composite endpoint, and 25.31% (p=0.274) and 6.91% (p=0.523) by EDSS. RR was 8.48% (p=0.739) and -9.45% (p=0.517) in Gd+ patients ≤50 and Gd- patients >50, respectively, for the composite endpoint, and 36.15% (p=0.145) and -6.68% (p=0.712) by EDSS. A weak trend for RR was also observed in the subgroup of relapsing patients for EDSS [relapsing: 19.50% (p=0.725); non-relapsing: 9.06% (p=0.370)].
Conclusion: The effects of fingolimod in this post hoc subgroup analysis indicate a possibility of a treatment effect in younger patients with Gd+ lesions or relapses, which can only be validated in a further trial, more focused on such patients. This observation is consistent with other studies in PPMS and suggests that in a subgroup of PPMS patients controlling for inflammatory disease activity may have some impact on progression.
Disclosure: Fred Lublin has received compensation for service on steering committees, data monitoring boards or as a consultant for Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi; Acorda; Questcor/Malinckrodt; Roche, Genentech; Celgene; Genzyme, MedImmune; Osmotica; Xenoport, Receptos; Forward Pharma; BBB technologies; Akros and is CoChief Editor of Multiple Sclerosis and Related Diseases.Mark S Freedman has received compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi‐Aventis, and Teva Canada Innovation.Bruce A C Cree has received personal compensation for consulting from Abbvie, Biogen, EMD Serono, Genzyme Sanofi, MedImmune, Novartis, Shire and Teva.Jerry S Wolinsky has received compensation for service on steering committees, data monitoring boards or as a consultant for AbbVie, Acetilon, Alkermes, Athersys, Inc., EMD Serono, Forward Pharma, Genentech, Genzyme, Novartis, Roche, Teva, toBBB and XenoPort. He has received research support from Genzyme, Sanofi, the National Institutes of Health and the National Multiple Sclerosis Society and royalties for monoclonal antibodies outlicensed to Chemicon International through the University of Texas Health Science Center at Houston.Howard L Weiner has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, and Teva Neuroscience as a consultant, speaker, or scientific advisory board member.Catherine Lubetzki has received personal compensation for activities with BiogenIdec, Novartis, Genzyme, Roche, Vertex.Hans-Peter Hartung has received honoraria for consulting, serving on steering committees and speaking at scientific symposia from Bayer, Biogen, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Octapharma, opexa, Roche, Teva , Sanofi with approval by the Rector of HeinrichHeineUniversity.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.Bernard MJ Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Pharmaceuticals, Genzyme and Roche as a consultant and as a scientific advisory board member.Ludwig Kappos´s institution has received in the last 3 years and used exclusively for research support: steering committee, advisory board, consultancy or speaker fees, or support of educational activities from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, and CSL Behring; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.David H Miller has received compensation for consulting from Biogen Idec, Novartis, GlaxoSmithKline, Bayer Schering Pharma, Genzyme, and Mitsubishi Pharma Europe and grants for central MRI analysis in MS trials from Novartis, Biogen Idec, Apitope and GlaxoSmithKline.Martin Merschhemke, Bingbing Li, Norman Putzki, and Dieter A Häring are employees of Novartis.