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      A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis

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          Abstract

          Background:

          As new therapies emerge which increase the risk of autoimmune disease it is increasingly important to understand the incidence of autoimmune disease in multiple sclerosis (MS).

          Objective:

          The purpose of this review is to estimate the incidence and prevalence of comorbid autoimmune disease in MS.

          Methods:

          The PUBMED, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched, and abstracts were independently screened by two reviewers. The data were abstracted by one reviewer using a standardized data collection form, and the findings were verified by a second reviewer. We assessed quality of the included studies using a standardized approach and conducted meta-analyses of population-based studies.

          Results:

          Sixty-one articles met the inclusion criteria. We observed substantial heterogeneity with respect to the populations studied, methods of ascertaining comorbidity, and reporting of findings. Based solely on population-based studies, the most prevalent autoimmune comorbidities were psoriasis (7.74%) and thyroid disease (6.44%). Our findings also suggest an increased risk of inflammatory bowel disease, likely uveitis and possibly pemphigoid.

          Conclusion:

          Fewer than half of the studies identified were of high quality. Population-based studies that report age, sex and ethnicity-specific estimates of incidence and prevalence are needed in jurisdictions worldwide.

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          Most cited references61

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          Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.

          The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial. In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00530348. 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 [95% CI 0·32-0·63]; p<0.0001), corresponding to a 54·9% improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78% of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard ratio 0·70 [95% CI 0·40-1·23]; p=0·22). 338 (90%) of patients in the alemtuzumab group had infusion-associated reactions; 12 (3%) of which were regarded as serious. Infections, predominantly of mild or moderate severity, occurred in 253 (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes infections (predominantly cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 (6%) in the interferon beta 1a group, and three (1%) had immune thrombocytopenia compared with none in the interferon beta 1a group. Two patients in the alemtuzumab group developed thyroid papillary carcinoma. Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. Genzyme (Sanofi) and Bayer Schering Pharma. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Epidemiology of autoimmune diseases in Denmark.

            An epidemiologic study of the autoimmune diseases taken together has not been done heretofore. The National Patient Register of Denmark is used to estimate the population prevalence of 31 possible or probable autoimmune diseases. Record linkage is used to estimate 465 pairwise co-morbidities in individuals among the 31 diseases, and familial aggregation among sibs, parents and offspring. The prevalence of any of the 31 diseases in the population is more than 5%. Within individuals, there is extensive comorbidity across the 31 diseases. Within families, aggregation is strongest for individual diseases and weak across diseases. These data confirm the importance of the autoimmune diseases as a group and suggest that common etiopathologies exist among them.
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              Environmental risk factors in multiple sclerosis aetiology.

              The epidemiology of multiple sclerosis (MS) has been intensively studied. It is conceptualised as a complex disease in which genetic and environmental factors act together to cause disease. There are temporal and geographic variations in disease risk, and risk of disease may be affected by migration between regions of differing risk. Numerous potential causal factors including infection, immunisations, physical and emotional stressors, climate, diet, and occupational exposures have been studied using various observational study designs. Thus far, no single environmental exposure has been consistently identified as a causal factor in MS, but sufficient data have accumulated that causal pathways should be postulated and tested. This review will focus on the environmental epidemiology of MS.
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                Author and article information

                Contributors
                Journal
                Mult Scler
                Mult. Scler
                MSJ
                spmsj
                Multiple Sclerosis (Houndmills, Basingstoke, England)
                SAGE Publications (Sage UK: London, England )
                1352-4585
                1477-0970
                March 2015
                March 2015
                : 21
                : 3 , Special Issue: International Workshop on Comorbidities in MS
                : 282-293
                Affiliations
                [1-1352458514564490]Departments of Internal Medicine and Community Health Sciences, University of Manitoba, Canada
                [2-1352458514564490]Departments of Internal Medicine and Community Health Sciences, University of Manitoba, Canada
                [3-1352458514564490]Mellen Center for MS Treatment and Research, Cleveland Clinic, USA
                [4-1352458514564490]Department of Neurology and Neurotherapeutics, University of Texas Southwestern, USA
                [5-1352458514564490]Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark
                [6-1352458514564490]Department of Biostatistics, University of Alabama at Birmingham, USA
                [7-1352458514564490]Scientific and Clinical Review Associates, LLC, USA
                [8-1352458514564490]Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Italy
                Author notes
                [*]Department of Internal Medicine, Department of Community Health Sciences, University of Manitoba, Health Sciences Center, GF-533, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada. rmarrie@ 123456hsc.mb.ca
                Article
                10.1177_1352458514564490
                10.1177/1352458514564490
                4429166
                25533299
                a64daef3-c0f5-4939-9ec7-953a3f0b18e8
                © The Author(s), 2015

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( http://www.uk.sagepub.com/aboutus/openaccess.htm).

                History
                : 18 August 2014
                : 23 November 2014
                : 25 November 2014
                Categories
                Systematic Review

                Immunology
                multiple sclerosis,comorbidity,autoimmune disease,incidence,prevalence
                Immunology
                multiple sclerosis, comorbidity, autoimmune disease, incidence, prevalence

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