Efficacy of intramuscular interferon beta-1a in patients with clinically isolated syndrome: analysis of subgroups based on new risk criteria

2009 ◽  
Vol 15 (6) ◽  
pp. 728-734 ◽  
Author(s):  
P O’Connor ◽  
RP Kinkel ◽  
M Kremenchutzky
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Functional System ◽  
Clinical Criteria ◽  
Presenting Symptoms ◽  
T2 Lesions ◽  
Magnetic Resonance Imaging Mri ◽  
Multifocal Disease ◽  
Mri Characteristics

Approximately 85% of multiple sclerosis (MS) cases begin as clinically isolated syndromes (CIS). Results from the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS) demonstrated that, in patients with CIS, treatment with intramuscular (IM) interferon beta-1a (IFNβ-1a) 30 μg once weekly delayed conversion to clinically definite MS (CDMS) in the total population and in subgroups based on presenting syndromes and baseline magnetic resonance imaging (MRI) characteristics. Changes to clinical and MRI risk classification of presenting symptoms in recent studies prompted reanalysis of CHAMPS data. Presenting syndromes were assessed using a derived algorithm that stratifies patients into mono- or multifocal categories based on functional system scores. The ability of IM IFNβ-1a to delay progression to CDMS in subgroups based on clinical presentation and MRI characteristics was assessed. Reanalysis of CHAMPS patients showed that 30% could be classified by clinical criteria as having multifocal disease at baseline. IM IFNβ-1a initiated at a first demyelinating attack delayed CDMS in monofocal patients ( P = 0.0013), patients with or without gadolinium-enhancing lesions ( P = 0.0007, P = 0.0405) and patients with at least nine T2 lesions at baseline ( P = 0.0044). These data confirm that IM IFNβ-1a delays conversion to CDMS in patients with CIS.

Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis

2013 ◽  
Vol 20 (5) ◽  
pp. 566-576 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Rosa Mancinelli ◽  
Laura De Giglio ◽  
Floriana De Angelis ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
European Medicines Agency ◽  
First Year ◽  
Resonance Imaging ◽  
T2 Lesions ◽  
Increased Risk ◽  
Magnetic Resonance Imaging Mri ◽  
One Year

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

scholarly journals Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

2015 ◽  
Vol 22 (2) ◽  
pp. 169-177 ◽  
Author(s):  
Iulia Potorac ◽  
Patrick Petrossians ◽  
Adrian F Daly ◽  
Franck Schillo ◽  
Claude Ben Slama ◽  
...  
Keyword(s):  
Large Population ◽  
Optic Chiasm ◽  
Research Priority ◽  
Maximal Diameter ◽  
Magnetic Resonance Imaging Mri ◽  
Multimodal Management ◽  
Mri Characteristics ◽  
Weighted Sequences ◽  
The Relationship

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P<0.0001), were associated with higher IGF1 levels (P=0.0001), invaded the cavernous sinus less frequently (P=0.0002), and rarely caused optic chiasm compression (P<0.0001). Acromegalic men tended to be younger at diagnosis than women (P=0.067) and presented higher IGF1 values (P=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (P=0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (P=0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether the T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.

Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging

2001 ◽  
Vol 7 (4) ◽  
pp. 221-226 ◽  
Author(s):  
Rakesh Sharma ◽  
Ponnada A Narayana ◽  
Jerry S Wolinsky
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Proton Magnetic Resonance ◽  
Magnetization Transfer ◽  
Spectroscopic Imaging ◽  
Magnetic Resonance Spectroscopic Imaging ◽  
Relapsing Remitting ◽  
Cortical Gray Matter ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Characteristics

Pathologically defined abnormalities in the cortical gray matter (GM) are well described in multiple sclerosis (MS) but are infrequently seen by conventional magnetic resonance imaging (MRI). We systematically evaluated 52 relapsing - remitting MS patients and 20 normal volunteers with high resolution MRI and short echo proton magnetic resonance spectroscopic imaging (MRSI). Individual tissue contributions to the spectroscopic voxels were estimated based on MRI that incorporated both CSF suppression and magnetization transfer, or double inversion images in which both CSF and GM were suppressed. Strong resonances in the 0.8 to 1.5 p.p.m. spectral region were observed in 13 MS patients. Image segmentation based on the MRI characteristics of tissues contributing to the spectroscopic voxels showed that these additional peaks originated mainly from GM. The presence of these additional peaks suggests that the normal appearance GM on MRI, is biochemically abnormal in a substantial proportion of relapsing-remitting MS patients.

Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization

2005 ◽  
Vol 11 (2) ◽  
pp. 227-231 ◽  
Author(s):  
Bernard MJ Uitdehaag ◽  
Ludwig Kappos ◽  
Lars Bauer ◽  
Mark S Freedman ◽  
David Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Clinical Findings ◽  
Large Trial ◽  
Mri Findings ◽  
Mcdonald Criteria ◽  
Magnetic Resonance Imaging Mri ◽  
Eligibility Assessment

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients. This paper describes these inconsistencies and their sources, and recommends a systematic approach that attempts to reduce the variability in interpreting clinical findings.

scholarly journals Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study

2018 ◽  
Vol 25 (6) ◽  
pp. 819-827 ◽  
Author(s):  
Gavin Giovannoni ◽  
Per Soelberg Sorensen ◽  
Stuart Cook ◽  
Kottil W Rammohan ◽  
Peter Rieckmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
High Disease Activity ◽  
Study Entry ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Study Population ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Objective: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Methods: Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). Results: In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Conclusion: Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria

2006 ◽  
Vol 12 (3) ◽  
pp. 281-286 ◽  
Author(s):  
E Portaccio ◽  
V Zipoli ◽  
G Siracusa ◽  
S Sorbi ◽  
M P Amato
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Interferon Beta ◽  
Clinical Criteria ◽  
Predictors Of Response ◽  
Lower Baseline ◽  
Disability Status ◽  
Relapsing Remitting ◽  
One Year ◽  
Relapsing Remitting Multiple Sclerosis

We assessed the proportion and potential predictors of response to interferon-beta (IFNβ) therapy in relapsing-remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNβ-1b subcutaneously (SC) (Betaferon), 59 IFNβ-1a intramuscularly (Avonex) and 55 IFNβ-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

scholarly journals Metabolomic Biomarkers of Multiple Sclerosis: A Systematic Review

2020 ◽  
Vol 7 ◽  
Author(s):  
Lachlan Porter ◽  
Alireza Shoushtarizadeh ◽  
George A. Jelinek ◽  
Chelsea R. Brown ◽  
Chai K. Lim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
High Throughput Sequencing ◽  
Cochrane Library ◽  
Clinical Criteria ◽  
Diagnosis And Prognosis ◽  
Csf Analysis ◽  
Potential Biomarker ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Biomarkers

BackgroundMagnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald’s clinical criteria are currently utilized tools in diagnosing multiple sclerosis. However, a more conclusive, consistent, and efficient way of diagnosing multiple sclerosis (MS) is yet to be discovered. A potential biomarker, discovered using advances in high-throughput sequencing such as nuclear magnetic resonance (NMR) spectroscopy and other “Omics”-based techniques, may make diagnosis and prognosis more reliable resulting in a more personalized and targeted treatment regime and improved outcomes. The aim of this review was to systematically search the literature for potential biomarkers from any bodily fluid that could consistently and accurately diagnose MS and/or indicate disease progression.MethodsA systematic literature review of EMBASE, PubMed (MEDLINE), The Cochrane Library, and CINAHL databases produced over a thousand potential studies. Inclusion criteria stated studies with potential biomarker outcomes for people with MS were to be included in the review. Studies were limited to those with human participants who had a clinically defined diagnosis of MS and published in English, with no limit placed on date of publication or the type of bodily fluid sampled.ResultsA total of 1,805 studies were recorded from the literature search. A total of 1,760 studies were removed based on their abstract, with a further 18 removed after considering the full text. A total of 30 studies were considered relevant and had their data retrieved and analyzed. Due to the heterogeneity of focus and results from the refined studies, a narrative synthesis was favored.ConclusionSeveral promising candidate biomarkers suitable for clinical application in MS have been studied. It is recommended follow-up studies with larger sample sizes be completed on several potential biomarkers.

scholarly journals Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials

2020 ◽  
Vol 13 ◽  
pp. 175628642096901
Author(s):  
Yinan Zhang ◽  
Natalia Gonzalez Caldito ◽  
Afsaneh Shirani ◽  
Amber Salter ◽  
Gary Cutter ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Meta Analysis ◽  
Group Level ◽  
T2 Lesions ◽  
Disease Modifying Therapies ◽  
Level Data ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing–remitting MS (RRMS). Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level. Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo. Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.

Clinical and MRI characteristics of multiple sclerosis in patients of Middle Eastern and North African ancestry residing in Ontario, Canada

2020 ◽  
pp. 135245852094821
Author(s):  
Estelle Seyman ◽  
Ashley Jones ◽  
Melanie Guenette ◽  
Reza Vosoughi ◽  
Daniel Selchen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Middle Eastern ◽  
African Ancestry ◽  
Genetic Determinants ◽  
Disability Progression ◽  
Disease Characteristics ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Characteristics ◽  
Age And Sex

Background: Multiple sclerosis (MS) incidence is rising in traditionally low-burden regions, including the Middle East and North Africa (MENA). Objectives: Our objective was to evaluate disease characteristics in MS patients of MENA descent (MENA-MS). Methods: MENA-MS patients and age- and sex-matched MS patients of European descent (EUR-MS) were identified through the MS Clinic Registry of St. Michael’s Hospital in Toronto, Canada. Disease activity and severity were evaluated by the annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, change in the Expanded Disability Status Scale (EDSS), progression index (PI), and MS Severity Score (MSSS). Results: All MS patients within the registry identified to be of MENA origin ( n = 192), and age- and sex-matched EUR-MS patients were included. Mean age was 42.9 years, 67% female. A total of 25% and 24% of EUR-MS and MENA-MS had progressive disease, with similar mean disease durations (11.5 and 11.4 years, respectively). Clinical and radiological disease activity (ARR, proportion with new/enlarging MRI lesions) was similar. MENA-MS showed greater disability progression over time (EDSS change = 0.24 vs. 0.06, p = 0.01), a higher MSSS (3.12 vs. 2.67, p = 0.04), and higher PI (0.34 vs. 0.27, p = 0.07). Conclusion: MENA-MS patients demonstrate higher disease severity compared to EUR-MS patients, despite having similar inflammatory measures of disease activity, with disability progression in the absence of relapses. These observations illustrate the importance of the intersections of environmental, socioeconomic, and genetic determinants in optimizing individualized MS care.

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