Contributions
Abstract: P1144
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Subcutaneous interferon β-1a (scIFNβ-1a) has been available since 1998, with approx. 1.44 million patient-years of exposure. Treatment with scIFNβ-1a after clinically isolated syndrome (CIS) increases the chance of having no evidence of disease activity (NEDA) vs delayed treatment (DT) after clinically definite multiple sclerosis (CDMS). This post-hoc analysis of REFLEX/REFLEXION assessed the impact of gadolinium-enhancing (Gd+) lesions at baseline on NEDA.
Methods: In REFLEX CIS patients were randomised to scIFNβ-1a 44 µg three times weekly (tiw), once weekly (qw) or placebo for 24 months; upon CDMS patients switched to open-label scIFNβ-1a tiw. In REFLEXION placebo patients switched to tiw (DT); scIFNβ-1a patients continued their initial regimen up to 60 months. This analysis used the integrated intent-to-treat REFLEX/REFLEXION population: tiw n=170; qw n=174; DT n=170. NEDA is defined as no relapses, disability worsening, new Gd+ lesions and new/enlarging T2 hyperintense lesions. To examine data without the influence of the 3-month MRI, time to first disease activity (FDA) event after 105 days post-randomisation (105d) was calculated. Kaplan-Meier curves and median times (95% confidence intervals [CI]) are presented with non-overlapping 95% CIs considered significant.
Results: In all patients, time to FDA event after 105d was significantly shorter in those with baseline Gd+ lesions (n=213) than without (n=301): 0.5 years (0.5-0.7) vs 1.0 year (0.8-1.4), respectively. In the higher risk group with baseline Gd+ lesions, scIFNβ-1a tiw increased the time to FDA (n=68; 0.7 years [0.5-1.2]) vs DT, but this was even longer in those without baseline Gd+ lesions (n=102; 1.7 years [1.5-2.0]). With scIFNβ-1a qw, time also differed significantly between patients with (n=72) and without (n=102) baseline Gd+ lesions: 0.7 years (0.5-0.8) vs 1.0 year (1.0-1.5). For DT, no statistical difference was seen for time between patients with (n=73) and without (n=97) baseline Gd+ lesions: 0.5 years (0.5-0.5) vs 0.7 years (0.5-0.7). In patients without baseline Gd+ lesions, differences in time between scIFNβ-1a tiw and qw vs DT were significant.
Conclusions: In CIS patients, presence of baseline Gd+ lesions was associated with a lower chance of remaining NEDA beyond the 3-month MRI vs those without baseline Gd+ lesions. Regardless of baseline Gd+ lesion status, early scIFNβ-1a treatment was associated with a higher chance of NEDA beyond the 3-month MRI than DT.
Disclosure: 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: Accordant, Acorda Therapeutics, Bayer HealthCare, Biogen, Celgene, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, Teva Pharmaceuticals USA. Received grants for clinical research from: Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, and Novartis.
JA: is an employee of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany.
KM: is an employee of Merck Gesellschaft mbH Austria, a business of Merck KGaA, Darmstadt, Germany.
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.
Abstract: P1144
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Subcutaneous interferon β-1a (scIFNβ-1a) has been available since 1998, with approx. 1.44 million patient-years of exposure. Treatment with scIFNβ-1a after clinically isolated syndrome (CIS) increases the chance of having no evidence of disease activity (NEDA) vs delayed treatment (DT) after clinically definite multiple sclerosis (CDMS). This post-hoc analysis of REFLEX/REFLEXION assessed the impact of gadolinium-enhancing (Gd+) lesions at baseline on NEDA.
Methods: In REFLEX CIS patients were randomised to scIFNβ-1a 44 µg three times weekly (tiw), once weekly (qw) or placebo for 24 months; upon CDMS patients switched to open-label scIFNβ-1a tiw. In REFLEXION placebo patients switched to tiw (DT); scIFNβ-1a patients continued their initial regimen up to 60 months. This analysis used the integrated intent-to-treat REFLEX/REFLEXION population: tiw n=170; qw n=174; DT n=170. NEDA is defined as no relapses, disability worsening, new Gd+ lesions and new/enlarging T2 hyperintense lesions. To examine data without the influence of the 3-month MRI, time to first disease activity (FDA) event after 105 days post-randomisation (105d) was calculated. Kaplan-Meier curves and median times (95% confidence intervals [CI]) are presented with non-overlapping 95% CIs considered significant.
Results: In all patients, time to FDA event after 105d was significantly shorter in those with baseline Gd+ lesions (n=213) than without (n=301): 0.5 years (0.5-0.7) vs 1.0 year (0.8-1.4), respectively. In the higher risk group with baseline Gd+ lesions, scIFNβ-1a tiw increased the time to FDA (n=68; 0.7 years [0.5-1.2]) vs DT, but this was even longer in those without baseline Gd+ lesions (n=102; 1.7 years [1.5-2.0]). With scIFNβ-1a qw, time also differed significantly between patients with (n=72) and without (n=102) baseline Gd+ lesions: 0.7 years (0.5-0.8) vs 1.0 year (1.0-1.5). For DT, no statistical difference was seen for time between patients with (n=73) and without (n=97) baseline Gd+ lesions: 0.5 years (0.5-0.5) vs 0.7 years (0.5-0.7). In patients without baseline Gd+ lesions, differences in time between scIFNβ-1a tiw and qw vs DT were significant.
Conclusions: In CIS patients, presence of baseline Gd+ lesions was associated with a lower chance of remaining NEDA beyond the 3-month MRI vs those without baseline Gd+ lesions. Regardless of baseline Gd+ lesion status, early scIFNβ-1a treatment was associated with a higher chance of NEDA beyond the 3-month MRI than DT.
Disclosure: 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: Accordant, Acorda Therapeutics, Bayer HealthCare, Biogen, Celgene, EMD Serono, Genentech/Roche, Genzyme/Sanofi, Novartis, Teva Pharmaceuticals USA. Received grants for clinical research from: Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, and Novartis.
JA: is an employee of EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany.
KM: is an employee of Merck Gesellschaft mbH Austria, a business of Merck KGaA, Darmstadt, Germany.
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.