Contributions
Abstract: P1025
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Subcutaneous interferon β-1a (scIFNβ-1a) treatment improves standard imaging outcomes vs placebo in clinically isolated syndrome (CIS) patients. We assessed whether scIFNβ-1a reduced new lesion evolution and temporal patterns using MRI data from REFLEX.
Methods: In REFLEX CIS patients were randomised to scIFNβ-1a 44µg three times weekly (tiw), once weekly (qw) or placebo for 24 months; upon clinically definite multiple sclerosis (MS) patients switched to open-label scIFNβ-1a tiw. Per protocol, scans were acquired every 3 months. This analysis included 393 patients (tiw n=128; qw n=137; placebo n=128) with scans available at least at Month (M) 12 and ≥2 scans after M12. The intensity of a new lesion on T1-weighted images without contrast was assessed at each timepoint, starting at its appearance, and classified as iso- or hypo-intense (black holes) with respect to the surrounding white matter. Lesions were also classified into four categories based on intensity at first appearance and M24: iso-iso, iso-hypo, hypo-iso, hypo-hypo. Mostly iso or hypo intensity was determined by assessing intensity at the majority of timepoints. Data are mean lesion numbers. Kruskal-Wallis tests were used to assess overall treatment effects and Mann-Whitney U tests for pairwise comparison treatments.
Results: There was a significant treatment effect on the numbers of new hypo- and iso-intense lesions at M24 (all p< 0.001). The number of new lesions that evolved into hypo-intense lesions at M24 was reduced vs placebo (4.0) with scIFNβ-1a tiw (1.4, p< 0.001) but not with qw (1.9, p=0.147). Both scIFNβ-1a doses significantly reduced the number of iso-iso and hypo-iso lesions vs placebo (all p< 0.001). The number of iso-hypo and hypo-hypo lesions was significantly reduced vs placebo (0.4 and 3.6, respectively) with scIFNβ-1a tiw (0.09, p=0.003; and 1.5, p< 0.001) but not with qw (0.13, p=0.052; and 1.8, p=0.165).
The number of lesions that were mostly hypo-intense was significantly reduced vs placebo (4.9) with tiw
(2.5, p=0.003) but not qw (2.7, p=0.273); the difference between tiw and qw was significant (p=0.025). Both scIFNβ-1a doses reduced the number of new lesions that were mostly iso-intense vs placebo
(all p< 0.001).
Conclusions: scIFNβ-1a tiw treatment reduced evolution of new lesions into black holes in CIS patients. As treatment was related to MS conversion by study design, further analyses investigating how these results impact MS conversion status are needed.
Disclosure: Funded by Merck KGaA, Darmstadt, Germany.
HV: has received research support from Merck Serono, Novartis, Pfizer, and Teva, and speaker honoraria from Novartis; all funds were paid to his institution.
MLdV: nothing to disclose.
MB: nothing to disclose.
GJN: has received personal compensation for activities with Bayer Healthcare Pharmaceuticals, and has received research support from Merck Serono.
BCdAT: nothing to disclose.
KM: is an employee of Merck Gesellschaft mbH Austria, a business of Merck KGaA, Darmstadt, Germany.
NDS: has received honoraria and consultation fees from Merck Serono S.A., Teva Pharmaceutical Industries, Novartis Pharma AG, BayerSchering AG, SanofiAventis and Serono Symposia International Foundation.
FB: has received honoraria/consultation fees from BayerSchering, Biogen, Merck Serono, Teva, Novartis, Roche, SanofiAventis and Serono Symposia International Foundation.
Abstract: P1025
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Subcutaneous interferon β-1a (scIFNβ-1a) treatment improves standard imaging outcomes vs placebo in clinically isolated syndrome (CIS) patients. We assessed whether scIFNβ-1a reduced new lesion evolution and temporal patterns using MRI data from REFLEX.
Methods: In REFLEX CIS patients were randomised to scIFNβ-1a 44µg three times weekly (tiw), once weekly (qw) or placebo for 24 months; upon clinically definite multiple sclerosis (MS) patients switched to open-label scIFNβ-1a tiw. Per protocol, scans were acquired every 3 months. This analysis included 393 patients (tiw n=128; qw n=137; placebo n=128) with scans available at least at Month (M) 12 and ≥2 scans after M12. The intensity of a new lesion on T1-weighted images without contrast was assessed at each timepoint, starting at its appearance, and classified as iso- or hypo-intense (black holes) with respect to the surrounding white matter. Lesions were also classified into four categories based on intensity at first appearance and M24: iso-iso, iso-hypo, hypo-iso, hypo-hypo. Mostly iso or hypo intensity was determined by assessing intensity at the majority of timepoints. Data are mean lesion numbers. Kruskal-Wallis tests were used to assess overall treatment effects and Mann-Whitney U tests for pairwise comparison treatments.
Results: There was a significant treatment effect on the numbers of new hypo- and iso-intense lesions at M24 (all p< 0.001). The number of new lesions that evolved into hypo-intense lesions at M24 was reduced vs placebo (4.0) with scIFNβ-1a tiw (1.4, p< 0.001) but not with qw (1.9, p=0.147). Both scIFNβ-1a doses significantly reduced the number of iso-iso and hypo-iso lesions vs placebo (all p< 0.001). The number of iso-hypo and hypo-hypo lesions was significantly reduced vs placebo (0.4 and 3.6, respectively) with scIFNβ-1a tiw (0.09, p=0.003; and 1.5, p< 0.001) but not with qw (0.13, p=0.052; and 1.8, p=0.165).
The number of lesions that were mostly hypo-intense was significantly reduced vs placebo (4.9) with tiw
(2.5, p=0.003) but not qw (2.7, p=0.273); the difference between tiw and qw was significant (p=0.025). Both scIFNβ-1a doses reduced the number of new lesions that were mostly iso-intense vs placebo
(all p< 0.001).
Conclusions: scIFNβ-1a tiw treatment reduced evolution of new lesions into black holes in CIS patients. As treatment was related to MS conversion by study design, further analyses investigating how these results impact MS conversion status are needed.
Disclosure: Funded by Merck KGaA, Darmstadt, Germany.
HV: has received research support from Merck Serono, Novartis, Pfizer, and Teva, and speaker honoraria from Novartis; all funds were paid to his institution.
MLdV: nothing to disclose.
MB: nothing to disclose.
GJN: has received personal compensation for activities with Bayer Healthcare Pharmaceuticals, and has received research support from Merck Serono.
BCdAT: nothing to disclose.
KM: is an employee of Merck Gesellschaft mbH Austria, a business of Merck KGaA, Darmstadt, Germany.
NDS: has received honoraria and consultation fees from Merck Serono S.A., Teva Pharmaceutical Industries, Novartis Pharma AG, BayerSchering AG, SanofiAventis and Serono Symposia International Foundation.
FB: has received honoraria/consultation fees from BayerSchering, Biogen, Merck Serono, Teva, Novartis, Roche, SanofiAventis and Serono Symposia International Foundation.