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Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.
The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).
Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).
The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”
The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”
EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.
Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.
The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).
Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).
The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”
The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”
EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.
Treatment of relapsing-remitting multiple sclerosis with interferon beta-1a produces a decline in brain volume over the first 3 months and follows a course consistent with pseudoatrophy that is likely caused by “hydrodynamic changes related to resolution of inflammation, edema, and cellular infiltration rather than the loss of actual brain tissue,” according to Michael G. Dwyer, Ph.D., of the State University of New York at Buffalo, and his coauthors.
The investigators’ open-label trial, which involved 23 relapsing-remitting multiple sclerosis (RRMS) patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls, is the first to study the effect of subcutaneous IFN beta-1a on early changes in brain volume and its relationship to changes in inflammatory markers (BMC Neurol. 2015 Nov 11;15:232. doi:10.1186/s12883-015-0488-9).
Dr. Dwyer and his colleagues did not find a loss in white matter as reported by previous studies investigating pseudoatrophy in the beginning of treatment for RRMS, but instead found that the atrophy was largely driven by gray matter loss. They observed significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months in RRMS patients, compared with controls, which was significantly correlated with decreased pro-inflammatory IL-17 F–expressing CD4-positive or CD8-positive T cells. Change in white matter volume experienced by IFN beta-1a–treated patients, compared with controls, did not differ at 3 months (–0.41%), from 3 to 6 months (0.30%), or from baseline to 6 months (–0.21%). The decrease in mean brain volume, however, slowed to just –0.08% from month 3 to 6, and was –0.91% from baseline to 6 months. Gray matter loss was not significant in RRMS patients from 3 to 6 months (–0.46%), but was significant from baseline to 6 months (–1.66%).
The lack of significant changes in white matter volume may have been affected, the investigators said, by a lack of statistical power to detect its change and the susceptibility of cortical gray matter measurement to “partial volume errors owing to its thin and convoluted nature.”
The findings are “supportive of an early anti-inflammatory therapeutic effect for IFN beta-1a,” the investigators wrote, and also send a message to use caution in applying MRI to measure disease progression via brain atrophy by having patients with RRMS with active disease who are starting on disease-modifying drug therapy obtain a baseline for MRI measures of brain volume “only after several months of therapy, once the pseudoatrophy effect has run its course, rather than at the beginning of therapy.”
EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.
FROM BMC NEUROLOGY
Key clinical point: Initial treatment of patients with relapsing-remitting multiple sclerosis with subcutaneous interferon beta-1a may cause a pseudoatrophy of the brain over the first 3 months of treatment that may be related to the resolution of inflammation.
Major finding: RRMS patients had a significant mean brain volume loss of –0.95% and gray matter loss of –1.52% in the first 3 months, compared with controls, but losses were no longer significant during 3-6 months.
Data source: An open-label study of 23 RRMS patients given interferon (IFN) beta-1a 44 mcg (Rebif) subcutaneously three times a week, and 15 healthy controls.
Disclosures: EMD Serono and Pfizer sponsored the study. Nine of the 13 authors had financial disclosures with companies that market MS drugs, including EMD Serono and Pfizer.
