Interferon-beta antibodies: implications for the treatment of MS.
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Antibodies↗
Biomedical subjects
Jerry S Wolinsky
Publications and source records attributed to Jerry S Wolinsky.
Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: meta-analysis of three double-blind, randomized, placebo-controlled clinical trials.
Three randomized, double-blind, placebo-controlled trials have shown that glatiramer acetate (GA) is effective in reducing relapse rate in patients with relapsing-remitting (RR) multiple sclerosis (MS). Using raw data pooled from 540 patients, we performed a meta-analysis of these three trials, to investigate whether the extent of GA efficacy varies according to disease-related variables at study entry. Three regression models were developed to assess the efficacy of GA on the annualized relapse rate (primary outcome measure), on the total number of on-trial relapses and on the time to first relapse. We also explored the efficacy of GA on accumulated disability and the potential role of baseline clinical variables as predictors of relapse-rate variables and treatment efficacy. The mean adjusted annualized relapse rate on study was 1.14 in the pooled placebo-treated subjects and 0.82 in the pooled GA group (P = 0.004), indicating an average reduction in annualized relapse rate of 28%. About a one third reduction of the total number of on-trial relapses was also observed in patients receiving GA (P < 0.0001), who had a median time to the first relapse of 322 days versus a median time to the first relapse of 219 days seen in those receiving placebo (P = 0.01). A beneficial effect on accumulated disability was also found (risk ratio of 0.6; 95%; CI = 0.4-0.9; P = 0.02). The drug assignment (P = 0.004), baseline EDSS score (P = 0.02) and number of relapses during the two years prior to study entry (P = 0.002) were significant predictors of on-trial annualized relapse rate. No other demographic or clinical variable at baseline significantly influenced the treatment effect. This meta-analysis reaffirms the effectiveness of GA in reducing relapse rate and disability accumulation in RRMS, at a magnitude comparable to that of other available immunomodulating treatments. It also suggests that GA efficacy is not significantly influenced by the patients' clinical characteristics at the time of treatment initiation.
Disability Evaluation↗
Short-term correlations between clinical and MR imaging findings in relapsing-remitting multiple sclerosis.
BACKGROUND AND PURPOSE: Despite extensive use of MR imaging to provide markers of multiple sclerosis (MS) activity and accumulated disease burden, the magnitude of the relationship between clinical and MR findings is still debated. Using data from the European/Canadian glatiramer acetate (GA) trial, we investigated short-term correlations between clinical and MR measures of disease activity in patients with relapsing-remitting MS (RRMS). METHODS: In a 9-month, double-blinded, placebo-controlled study, 239 patients with RRMS were randomly assigned to receive 20 mg GA (n = 119) or placebo (n = 120). Clinical assessment included monthly neurologic examinations with Expanded Disability Status Scale scoring and visits for symptoms suggestive of relapse. Dual-echo T2-weighted and pre- and postcontrast T1-weighted brain MR images were obtained at baseline and monthly during follow-up. Contrast-enhancing and new T2-hyperintense lesions were counted, and total T2-hyperintense and T1-hypointense lesion volumes were measured. RESULTS: Significant univariate correlations were found between the number of relapses during the study period and the number of enhancing lesions at baseline (r = 0.25) and during follow-up (r = 0.30) in the study population as a whole. Multivariable analysis showed that two independent factors were more strongly correlated with relapse frequency: the number of relapses during the 2 years before entry and the number of on-trial enhancing lesions, in the whole study population and in the placebo group. CONCLUSION: In RRMS, MR imaging measures of inflammatory activity are modestly but significantly correlated with the occurrence of clinical attacks over the short term. Clinical and MR imaging assessment can provide complementary outcome measures for RRMS trials.
Adult↗
Magnetic resonance spectroscopy in multiple sclerosis: window into the diseased brain.
Magnetic resonance spectroscopy provides noninvasive insight into the regional and global biochemical alterations that are concomitants of the dynamic processes that underlie the evolution of fundamental pathologic changes in multiple sclerosis. These include now well-recognized alterations of neuronal biochemical markers that accompany tissue destruction readily visualized by magnetic resonance imaging, but also dynamic changes in several metabolites that indicate pathological processes that precede the magnetic resonance imaging-defined lesion, or completely escape current high-resolution imaging.
Biomarkers↗
Phase-sensitive T1 inversion recovery imaging: a time-efficient interleaved technique for improved tissue contrast in neuroimaging.
BACKGROUND AND PURPOSE: High tissue contrast and short acquisition time are desirable when scanning patients. The purpose of this report is to describe the implementation of a new technique for generating high gray matter (GM) and white matter (WM) contrast in a short scan time, make a quantitative evaluation of the contrast efficiency, and explore its potential applications in neuroimaging. METHOD: A fully interleaved T1-weighted inversion recovery (T1IR) sequence with phase-sensitive reconstruction (PS-T1IR) is implemented. This sequence is compared with conventional T1-weighted spin-echo imaging (T1SE) and T1-weighted fluid-attenuated inversion recovery (T1FLAIR). The time efficiency and contrast enhancement have been quantitatively analyzed in normal volunteers. The performance of the sequence is evaluated in >30 patients with neurologic disorders. The sensitivity of PS-T1IR relative to T1SE in detecting gadolinium enhancements is also evaluated. RESULTS: PS-T1IR is more time-efficient than T1SE and generates better GM-WM contrast. It results in the best contrast-to-noise ratio (CNR) efficiency (1.16) compared with T1FLAIR (0.73) and T1SE (0.23). For a typical clinical protocol, PS-T1IR takes only 1:30 minutes versus 2:40 minutes for T1SE imaging for the whole brain coverage. Although gadolinium enhancements are detected with comparable sensitivity on both PS-T1IR and T1SE sequences, in certain instances, the latter sequence appears to be more sensitive in demonstrating gadolinium enhancements within WM. CONCLUSION: PS-T1IR has the highest CNR efficiency compared with T1FLAIR and T1SE. It is a very practical technique for neuroradiologic applications.
Brain Diseases↗