Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis (original) (raw)
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European Journal of Neurology, 2002
There are few long-term clinical and magnetic resonance imaging (MRI) data on patients treated with interferon-beta (IFN-b) for relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to provide clinical and MRI data on 68 patients with RRMS treated over a 6-year period and to investigate whether a baseline MRI predicts their long-term clinical and MRI outcome. Six MRI scans were performed monthly before treatment and a further 13 scans were performed during treatment with IFN-b, the last of which 6 years after commencement of treatment. The relapse rate, disability as measured by the Expanded Disability Status Scale (EDSS), and MRI parameters, including Gd-enhancing lesion load (Gd-LL), T2 hyperintense lesion load (T2-LL) T1 hypointense lesion load (T1-LL) and supratentorial brain volume (SBV) were measured throughout the study. The mean annual relapse rate over the 6 years was 0.52 (SD 0.67), which is significantly lower (68.6%) than the mean annual relapse rate of 1.6 observed during the 2-year period before the commencement of treatment (P < 0.01). The median EDSS score increased from 2 to 2.5, remaining stable in 60% of the patients. From the baseline scan to the final scan, there was a median increase of 7% in the T2-LL and 23.9% in the T1-LL, whilst SBV decreased by 2.7%. The increase in the EDSS over the course of the study was significantly correlated with a reduction in brain volume (r ¼ 0.46, P ¼ 0.001). Greater brain damage at baseline, as measured by both T2-LL and T1-LL, was significantly associated with an increase in disability over the 6 years (r ¼ 0.44, P ¼ 0.0009; r ¼ 0.50, P ¼ 0.0007, respectively). This study shows a sustained effect of IFN-b on the relapse rate, which is lower than during the 2 years before treatment commencement. More than half the patients showed an improvement or stabilization in the EDSS score. The increment in disability was correlated with the development of brain atrophy but not with increases in lesion burden. Finally, the finding that the extent of lesion burden at the baseline was a strong predictor of increasing disability suggests that IFN-b treatment might have a moderate effect in modifying the multiple sclerosis (MS) disease course over 6 years unless preventive treatment is started early.
One-year MRI scan predicts clinical response to interferon beta in multiple sclerosis
European Journal of Neurology, 2009
Background and purpose: To define the predictive value of clinical and magnetic resonance imaging (MRI) characteristics in identifying relapsing-remitting multiple sclerosis (RR-MS) patients with sustained disability progression during interferon beta (IFNB) treatment. Methods: All patients receiving treatment with one of the available IFNB formulations for at least 1 year were included in this single-centre, prospective and postmarketing study. Demographic, clinical and MRI data were collected at IFNB start and at 1 year of therapy; patients were followed-up at least yearly. Poor clinical response was defined as the occurrence of a sustained disability progression of ‡1 point in the Expanded Disability Status Scale (EDSS) during the follow-up period. Results: Out of 454 RR-MS patients starting IFNB therapy, data coming from 394 patients with a mean follow-up of 4.8 (2.4) years were analysed. Sixty patients were excluded because of too short follow-up. Less than 1/3 (30.4%) of the patients satisfied the criterion of Ôpoor respondersÕ. Patients presenting new lesions on T2-weighted MRI scan after 1 year of therapy (compared with baseline) had a higher risk of being poor responder to treatment with IFNB during the follow-up period (HR 16.8, 95% CI 7.6-37.1, P < 0.001). An augmented risk increasing the number of lesions was observed, with a 10-fold increase for each new lesion. Conclusions: Developing new T2-hyperintense lesions during IFNB treatment was the best predictor of long-term poor response to therapy. MRI scans performed after 1 year of IFNB treatment may be useful in contributing to early identification of poor responders.
European Journal of Clinical Pharmacology
Purpose During interferon-β (IFN-β) therapy, up to 45 % of patients may develop neutralizing antibodies (NAbs), associated with a decreased efficacy of the drug. We investigated in a real-life setting the impact of NAbs on magnetic resonance imaging (MRI) outcomes in a population of 567 IFN-β-treated relapsing-remitting (RR) multiple sclerosis (MS) patients up to 7 years. We also evaluated NAbs' role as a biomarker of the persistence of MRI disease activity. Methods Patients' sera were tested for NAbs' presence by cytopathic effect (CPE) assay every 6-12 months. MRI scans were performed every 12 months. Generalized hierarchical linear models accounting for within-patient correlation were used to analyze T1 gadolinium-enhancing and new T2 lesions. Moreover, further tests were carried out to assess the overall outcome difference from year 1 to year 7 according to NAb status and the possible interaction between NAb status and time of follow-up. Results Seventy-five patients (13.2 %) became NAb positive (NAb+) during the follow-up. Considering T1 gadoliniumenhancing (GD+) lesions, we observed a significantly higher incidence in NAb+ patients (52 %, p = 0.0091). Also for new T2 lesions, we found a higher incidence in NAb+ patients (50 %, p = 0.0075). The negative impact of NAbs on the MRI outcomes considered did not change during the follow-up. Conclusions Our 7-year results show the negative effect of NAbs on MRI measures of disease activity and confirm their role as a surrogate marker of IFN-β treatment efficacy.
Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS
Neurology(R) neuroimmunology & neuroinflammation, 2015
To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon β-1a (IFN-β-1a). Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) received IFN-β-1a for 6 months. Immunologic marker results were correlated with brain MRI lesion volumes, and volumes of normal-appearing brain tissue (NABT) with decreasing or increasing voxel-wise magnetization transfer ratio (VW-MTR), suggestive of demyelination and remyelination, respectively. Baseline expression of Th22 cell transcription factor aryl hydrocarbon receptor (AHR) and interleukin (IL)-17F, and percentages of IL-22-expressing CD4(+) and CD8(+) cells, were significantly higher in patients vs 15 healthy controls; IL-4 in CD4(+) cells was lower. Baseline percentage of IL-22-producing CD8(+) cells positively correlated with T2 lesion volumes, while percentage of IL-17A-producing CD8(+) cells positively correlated with T2 and T1 lesion volumes...
Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study
Multiple Sclerosis, 2003
). The purpo se o f this study was to evaluate safety, to lerability and effects on MRI lesions o f three different do ses o f oral IFNB-1a co mpared with placebo o ver six mo nths in relapsing ¡/remitting (RR) MS patients. Methods: In this multicenter, do uble-blind randomized trial, RR ¡/MS patients received 0.06, 0.6 or 6 million inter natio nal units (MIU) IFNB-1a o r placebo every o ther day for up to six mo nths. G adolinium DTPAenhanced brain MRI scans were per formed at screening and mo nthly during treatment. The primar y variable was the cumulative number o f new ly active lesions. Seco ndary variables included volume o f enhancing lesions o n T1-weighted images each month and lesion volume o n T2-weighted images at months three and six. Safety measures included adverse events, laborator y variables, vital signs, EC G , physical examinatio n, EDSS and number of relapses. Neo pterin was measured in 21 patients and neutr alizing antibo dies in 24 patients. Results: O f 194 screened patients, 173 were rando mized (42¡/44 patients per gro up) in 15 center s. Median cumulative number s o f new ly active lesions o ver six mo nths were 4.0 in the placebo and 0.6 MIU gro ups, co mpared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Seco ndary efficacy endpo ints showed small and inconsistent differences between groups. A dverse events showed no no table group differences. A ppro ximately two -thir ds o f patients in each group remained relapse free. N o patients showed neutr alizing antibo dies. N eo pter in levels were co mparable betw een gro ups. Conclusion: O ral IFNB-1a showed neither beneficial effects in RRMS no r any systemic bio lo gical effects. Treatment was safe and well to lerated. Multiple Sclerosis (2003) 9, 342¡/348