Contributions
Abstract: P689
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Patients treated with subcutaneous interferon (scIFN) β-1a after clinically isolated syndrome (CIS) are more likely to achieve no evidence of disease activity up to 5 years than those treated after clinically definite multiple sclerosis. This study aimed to determine the effect of once weekly (qw) or three times weekly (tiw) scIFN β-1a vs delayed treatment (DT) after CIS on no evidence of radiological or clinical activity up to 2 and 5 years.
Methods: In REFLEX, patients with CIS were randomized to double-blind scIFN β-1a 44 µg tiw, qw, or placebo for 24 months (upon clinically-definite multiple sclerosis, patients switched to open-label scIFN β-1a tiw). In REFLEXION, placebo patients switched to tiw (DT); scIFN β-1a patients continued their initial qw/tiw regimen for up to 60-months post-randomization. This post-hoc analysis was conducted in the integrated intent-to-treat REFLEX plus REFLEXION population (tiw, n=171; qw, n=175; DT, n=171).
All p values are nominal.
Results: A numerically greater proportion of patients treated tiw than qw or with DT were radiological activity-free up to years 2 and 5 (2 years: tiw 29%, qw 18%, DT 9%; 5 years: tiw 12%, qw 4%, DT 1%). Up to years 2 and 5, the odds ratios of being radiological activity-free were higher for tiw than qw vs DT
(2 years: tiw 4.11 [p< 0.0001], qw 2.14 [p=0.02]; 5 years: tiw 11.53 [p=0.0012], qw 3.55 [p=0.1]). Beyond 2 years, the proportions who were clinical activity-free in each treatment arm were similar (2 years: tiw 68%, qw 69%, DT 56%; 5 years tiw 37%, qw 42%, DT 36%). The odds ratios of being clinical activity-free were higher for tiw and qw up to 2 years vs DT but not up to 5 years (2 years: tiw 1.69 [p=0.02], qw 1.79 [p< 0.001]; 5 years: tiw 1.05, [p=0.8], qw 1.29 [p=0.2]). In patients with true CIS (McDonald 2010 criteria), the respective proportions radiological activity-free up to 2 years and 5 years were numerically greater for tiw vs qw and DT (2 years: 32% vs 20% vs 10%; 5 years: 9% vs 3% vs 1%). In patients with McDonald 2010 relapsing remitting multiple sclerosis, the proportions radiological activity-free were also numerically greater for tiw vs qw and DT (2 years: 13% vs 9% vs 3%; 5 years: 5% vs 2% vs 0%).
Conclusions: Early treatment with scIFN β-1a tiw led to greater likelihood of freedom from radiological disease activity vs DT up to 5 years post-randomization. The advantage of tiw or qw on freedom from clinical disease activity vs DT was seen up to 2 years.
Disclosure: Study supported by Merck KGaA, Darmstadt, Germany.
MSF: honoraria or consultation fees from Actelion, Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Hoffman La Roche, Novartis, Sanofi, Teva.
GC: honoraria and consultation fees from Serono Symposia International Foundation, EMD Serono, Novartis, Teva Pharmaceutical Industries, Sanofi-Aventis, Bayer Schering, and Biogen Dompè.
PC: advisor or consultant for: AbbVie Inc.; Accordant; Acorda Therapeutics; Bayer HealthCare Pharmaceuticals; Biogen; EMD Serono, Inc.; Genentech/Roche; Genzyme/Sanofi; Novartis Pharmaceuticals Corporation; Teva Pharmaceuticals USA. Received grants for clinical research from: Actelion Pharmaceuticals, Ltd; Biogen; Genentech/Roche; Novartis Pharmaceuticals Corporation; Opexa Therapeutics, Inc.
LK"s institution (University Hospital Basel): research support from Actelion, Addex, Bayer, Biogen, Biotica, CSL Behring, Genzyme, Lilly, Merck, Mitsubishi, Neurostatus Systems, Novartis, Ono Pharma, Pfizer, Receptos, Roche, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, the European Union, the Roche Research Foundation, the Swiss MS Society, the Swiss National Research Foundation.
KM: is an employee of Merck KGaA.
LC: is an employee of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany.
Abstract: P689
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Patients treated with subcutaneous interferon (scIFN) β-1a after clinically isolated syndrome (CIS) are more likely to achieve no evidence of disease activity up to 5 years than those treated after clinically definite multiple sclerosis. This study aimed to determine the effect of once weekly (qw) or three times weekly (tiw) scIFN β-1a vs delayed treatment (DT) after CIS on no evidence of radiological or clinical activity up to 2 and 5 years.
Methods: In REFLEX, patients with CIS were randomized to double-blind scIFN β-1a 44 µg tiw, qw, or placebo for 24 months (upon clinically-definite multiple sclerosis, patients switched to open-label scIFN β-1a tiw). In REFLEXION, placebo patients switched to tiw (DT); scIFN β-1a patients continued their initial qw/tiw regimen for up to 60-months post-randomization. This post-hoc analysis was conducted in the integrated intent-to-treat REFLEX plus REFLEXION population (tiw, n=171; qw, n=175; DT, n=171).
All p values are nominal.
Results: A numerically greater proportion of patients treated tiw than qw or with DT were radiological activity-free up to years 2 and 5 (2 years: tiw 29%, qw 18%, DT 9%; 5 years: tiw 12%, qw 4%, DT 1%). Up to years 2 and 5, the odds ratios of being radiological activity-free were higher for tiw than qw vs DT
(2 years: tiw 4.11 [p< 0.0001], qw 2.14 [p=0.02]; 5 years: tiw 11.53 [p=0.0012], qw 3.55 [p=0.1]). Beyond 2 years, the proportions who were clinical activity-free in each treatment arm were similar (2 years: tiw 68%, qw 69%, DT 56%; 5 years tiw 37%, qw 42%, DT 36%). The odds ratios of being clinical activity-free were higher for tiw and qw up to 2 years vs DT but not up to 5 years (2 years: tiw 1.69 [p=0.02], qw 1.79 [p< 0.001]; 5 years: tiw 1.05, [p=0.8], qw 1.29 [p=0.2]). In patients with true CIS (McDonald 2010 criteria), the respective proportions radiological activity-free up to 2 years and 5 years were numerically greater for tiw vs qw and DT (2 years: 32% vs 20% vs 10%; 5 years: 9% vs 3% vs 1%). In patients with McDonald 2010 relapsing remitting multiple sclerosis, the proportions radiological activity-free were also numerically greater for tiw vs qw and DT (2 years: 13% vs 9% vs 3%; 5 years: 5% vs 2% vs 0%).
Conclusions: Early treatment with scIFN β-1a tiw led to greater likelihood of freedom from radiological disease activity vs DT up to 5 years post-randomization. The advantage of tiw or qw on freedom from clinical disease activity vs DT was seen up to 2 years.
Disclosure: Study supported by Merck KGaA, Darmstadt, Germany.
MSF: honoraria or consultation fees from Actelion, Bayer HealthCare, Biogen Idec, Chugai, EMD Canada, Genzyme, Hoffman La Roche, Novartis, Sanofi, Teva.
GC: honoraria and consultation fees from Serono Symposia International Foundation, EMD Serono, Novartis, Teva Pharmaceutical Industries, Sanofi-Aventis, Bayer Schering, and Biogen Dompè.
PC: advisor or consultant for: AbbVie Inc.; Accordant; Acorda Therapeutics; Bayer HealthCare Pharmaceuticals; Biogen; EMD Serono, Inc.; Genentech/Roche; Genzyme/Sanofi; Novartis Pharmaceuticals Corporation; Teva Pharmaceuticals USA. Received grants for clinical research from: Actelion Pharmaceuticals, Ltd; Biogen; Genentech/Roche; Novartis Pharmaceuticals Corporation; Opexa Therapeutics, Inc.
LK"s institution (University Hospital Basel): research support from Actelion, Addex, Bayer, Biogen, Biotica, CSL Behring, Genzyme, Lilly, Merck, Mitsubishi, Neurostatus Systems, Novartis, Ono Pharma, Pfizer, Receptos, Roche, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, the European Union, the Roche Research Foundation, the Swiss MS Society, the Swiss National Research Foundation.
KM: is an employee of Merck KGaA.
LC: is an employee of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany.