Long-term clinical outcomes in patients with CIS treated with interferon beta-1b: first results from BENEFIT 15
ECTRIMS Learn. Kappos L. 10/12/18; 228126; P1748
Prof. Dr. Ludwig Kappos
Contributions
Contributions
Abstract
Abstract: P1748
Type: Poster Sessions
Abstract Category: N/A
Background: Early treatment with interferon beta-1b, after clinically isolated syndrome (CIS), has proven beneficial in the short term, but long-term data especially beyond 10 years, are limited in this population.
Objective: To study long-term (15-year) outcomes of treatment with interferon beta-1b at or within <= 2 years after CIS.
Methods: Patients with CIS and >=2 MRI lesions suggestive of MS were randomly assigned to receive interferon beta-1b (early treatment) or placebo. After 2 years or conversion to clinically definite MS (CDMS, defined as a second clinical attack or sustained neurological progression), patients on placebo were offered treatment with interferon beta-1b (delayed treatment). Blinded prospective assessments continued for 5 years. Fifteen years after the initial randomization, all patients from participating study centers were approached to complete a comprehensive clinical and MRI reassessment.
Results: 261/468 initially randomized patients were enrolled (n=161 early, n=100 delayed). With 6 patients known to be deceased, information on 267 was available (57.1% of the original cohort and 67.1% of patients from the 73 participating or contributing sites out of 98 randomizing sites). Mean observation time was 15.2 years with a mean 1.5-year delay in start of treatment in the delayed group. The annualized relapse rate in the full analysis set was 0.18 over 15 years; risk of relapse in the early treatment group was 18.9% lower than in the delayed treatment group (ARR 0.167 vs 0.20, P=.0447), Kaplan-Meier estimate for conversion to CDMS by Year 15 was 69.8% (30.5% lower risk for the early vs the delayed group; P=.0029). Mean (SD) PASAT score at 15 years was 51.5 (11) in the early and 51.1(9) in the delayed group (P=.0036 for treatment effect over 15 years). In the overall BENEFIT 15 cohort, mean (SD) EDSS score was 2.49 (1.76); median (Q1, Q3) 2.0 (1.0, 3.5) (EDSS 0-2.5: 161 patients [62.2%], 3.0-5.5: 79 [30.5%], 6.0-6.5: 12 [4.6%], >=7: 7 [2.7%]).
Conclusions: BENEFIT 15 is a unique study cohort with 15-year follow up from randomization in a clinical study of early or delayed treatment with interferon beta-1b in patients presenting with CIS. Results support a sustained benefit of early intervention in reducing the risk of relapse and conversion to CDMS. The fact that both groups showed little or no disease progression as indicated by low EDSS and high PASAT scores further supports the value of starting interferon beta-1b treatment at or shortly after CIS.
Disclosure: L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; license fees for Neurostatus products; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibod
MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
R Koelbach is a salaried employee of PAREXEL International.
EM Wicklein is a salaried employee of Bayer AG.
Keywords: CIS, RRMS, interferon beta-1b, disease-modifying therapy
Type: Poster Sessions
Abstract Category: N/A
Background: Early treatment with interferon beta-1b, after clinically isolated syndrome (CIS), has proven beneficial in the short term, but long-term data especially beyond 10 years, are limited in this population.
Objective: To study long-term (15-year) outcomes of treatment with interferon beta-1b at or within <= 2 years after CIS.
Methods: Patients with CIS and >=2 MRI lesions suggestive of MS were randomly assigned to receive interferon beta-1b (early treatment) or placebo. After 2 years or conversion to clinically definite MS (CDMS, defined as a second clinical attack or sustained neurological progression), patients on placebo were offered treatment with interferon beta-1b (delayed treatment). Blinded prospective assessments continued for 5 years. Fifteen years after the initial randomization, all patients from participating study centers were approached to complete a comprehensive clinical and MRI reassessment.
Results: 261/468 initially randomized patients were enrolled (n=161 early, n=100 delayed). With 6 patients known to be deceased, information on 267 was available (57.1% of the original cohort and 67.1% of patients from the 73 participating or contributing sites out of 98 randomizing sites). Mean observation time was 15.2 years with a mean 1.5-year delay in start of treatment in the delayed group. The annualized relapse rate in the full analysis set was 0.18 over 15 years; risk of relapse in the early treatment group was 18.9% lower than in the delayed treatment group (ARR 0.167 vs 0.20, P=.0447), Kaplan-Meier estimate for conversion to CDMS by Year 15 was 69.8% (30.5% lower risk for the early vs the delayed group; P=.0029). Mean (SD) PASAT score at 15 years was 51.5 (11) in the early and 51.1(9) in the delayed group (P=.0036 for treatment effect over 15 years). In the overall BENEFIT 15 cohort, mean (SD) EDSS score was 2.49 (1.76); median (Q1, Q3) 2.0 (1.0, 3.5) (EDSS 0-2.5: 161 patients [62.2%], 3.0-5.5: 79 [30.5%], 6.0-6.5: 12 [4.6%], >=7: 7 [2.7%]).
Conclusions: BENEFIT 15 is a unique study cohort with 15-year follow up from randomization in a clinical study of early or delayed treatment with interferon beta-1b in patients presenting with CIS. Results support a sustained benefit of early intervention in reducing the risk of relapse and conversion to CDMS. The fact that both groups showed little or no disease progression as indicated by low EDSS and high PASAT scores further supports the value of starting interferon beta-1b treatment at or shortly after CIS.
Disclosure: L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; license fees for Neurostatus products; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibod
MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
R Koelbach is a salaried employee of PAREXEL International.
EM Wicklein is a salaried employee of Bayer AG.
Keywords: CIS, RRMS, interferon beta-1b, disease-modifying therapy
Abstract: P1748
Type: Poster Sessions
Abstract Category: N/A
Background: Early treatment with interferon beta-1b, after clinically isolated syndrome (CIS), has proven beneficial in the short term, but long-term data especially beyond 10 years, are limited in this population.
Objective: To study long-term (15-year) outcomes of treatment with interferon beta-1b at or within <= 2 years after CIS.
Methods: Patients with CIS and >=2 MRI lesions suggestive of MS were randomly assigned to receive interferon beta-1b (early treatment) or placebo. After 2 years or conversion to clinically definite MS (CDMS, defined as a second clinical attack or sustained neurological progression), patients on placebo were offered treatment with interferon beta-1b (delayed treatment). Blinded prospective assessments continued for 5 years. Fifteen years after the initial randomization, all patients from participating study centers were approached to complete a comprehensive clinical and MRI reassessment.
Results: 261/468 initially randomized patients were enrolled (n=161 early, n=100 delayed). With 6 patients known to be deceased, information on 267 was available (57.1% of the original cohort and 67.1% of patients from the 73 participating or contributing sites out of 98 randomizing sites). Mean observation time was 15.2 years with a mean 1.5-year delay in start of treatment in the delayed group. The annualized relapse rate in the full analysis set was 0.18 over 15 years; risk of relapse in the early treatment group was 18.9% lower than in the delayed treatment group (ARR 0.167 vs 0.20, P=.0447), Kaplan-Meier estimate for conversion to CDMS by Year 15 was 69.8% (30.5% lower risk for the early vs the delayed group; P=.0029). Mean (SD) PASAT score at 15 years was 51.5 (11) in the early and 51.1(9) in the delayed group (P=.0036 for treatment effect over 15 years). In the overall BENEFIT 15 cohort, mean (SD) EDSS score was 2.49 (1.76); median (Q1, Q3) 2.0 (1.0, 3.5) (EDSS 0-2.5: 161 patients [62.2%], 3.0-5.5: 79 [30.5%], 6.0-6.5: 12 [4.6%], >=7: 7 [2.7%]).
Conclusions: BENEFIT 15 is a unique study cohort with 15-year follow up from randomization in a clinical study of early or delayed treatment with interferon beta-1b in patients presenting with CIS. Results support a sustained benefit of early intervention in reducing the risk of relapse and conversion to CDMS. The fact that both groups showed little or no disease progression as indicated by low EDSS and high PASAT scores further supports the value of starting interferon beta-1b treatment at or shortly after CIS.
Disclosure: L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; license fees for Neurostatus products; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibod
MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
R Koelbach is a salaried employee of PAREXEL International.
EM Wicklein is a salaried employee of Bayer AG.
Keywords: CIS, RRMS, interferon beta-1b, disease-modifying therapy
Type: Poster Sessions
Abstract Category: N/A
Background: Early treatment with interferon beta-1b, after clinically isolated syndrome (CIS), has proven beneficial in the short term, but long-term data especially beyond 10 years, are limited in this population.
Objective: To study long-term (15-year) outcomes of treatment with interferon beta-1b at or within <= 2 years after CIS.
Methods: Patients with CIS and >=2 MRI lesions suggestive of MS were randomly assigned to receive interferon beta-1b (early treatment) or placebo. After 2 years or conversion to clinically definite MS (CDMS, defined as a second clinical attack or sustained neurological progression), patients on placebo were offered treatment with interferon beta-1b (delayed treatment). Blinded prospective assessments continued for 5 years. Fifteen years after the initial randomization, all patients from participating study centers were approached to complete a comprehensive clinical and MRI reassessment.
Results: 261/468 initially randomized patients were enrolled (n=161 early, n=100 delayed). With 6 patients known to be deceased, information on 267 was available (57.1% of the original cohort and 67.1% of patients from the 73 participating or contributing sites out of 98 randomizing sites). Mean observation time was 15.2 years with a mean 1.5-year delay in start of treatment in the delayed group. The annualized relapse rate in the full analysis set was 0.18 over 15 years; risk of relapse in the early treatment group was 18.9% lower than in the delayed treatment group (ARR 0.167 vs 0.20, P=.0447), Kaplan-Meier estimate for conversion to CDMS by Year 15 was 69.8% (30.5% lower risk for the early vs the delayed group; P=.0029). Mean (SD) PASAT score at 15 years was 51.5 (11) in the early and 51.1(9) in the delayed group (P=.0036 for treatment effect over 15 years). In the overall BENEFIT 15 cohort, mean (SD) EDSS score was 2.49 (1.76); median (Q1, Q3) 2.0 (1.0, 3.5) (EDSS 0-2.5: 161 patients [62.2%], 3.0-5.5: 79 [30.5%], 6.0-6.5: 12 [4.6%], >=7: 7 [2.7%]).
Conclusions: BENEFIT 15 is a unique study cohort with 15-year follow up from randomization in a clinical study of early or delayed treatment with interferon beta-1b in patients presenting with CIS. Results support a sustained benefit of early intervention in reducing the risk of relapse and conversion to CDMS. The fact that both groups showed little or no disease progression as indicated by low EDSS and high PASAT scores further supports the value of starting interferon beta-1b treatment at or shortly after CIS.
Disclosure: L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; license fees for Neurostatus products; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibod
MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
R Koelbach is a salaried employee of PAREXEL International.
EM Wicklein is a salaried employee of Bayer AG.
Keywords: CIS, RRMS, interferon beta-1b, disease-modifying therapy
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