574151

editorial2015

MSJ0010.1177/1352458515574151Multiple Sclerosis JournalCulpepper

MULTIPLE SCLEROSIS MSJ JOURNAL

Editorial

The incidence and prevalence of comorbidity in multiple sclerosis

Multiple Sclerosis Journal 1­–2 DOI: 10.1177/ 1352458515574151 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav

William J Culpepper II

It is generally accepted that comorbidity, the presence of one or more co-occurring conditions or diseases, increases with age, and is common in patients with a chronic disease such as multiple sclerosis (MS). And, more importantly, that comorbidity can have many effects such as diagnostic delays, selection of treatment and their outcomes, as well as worsening quality of life, to name a few. However, it is only relatively recently that there has been a focused awareness and interest in the impact of comorbid conditions in MS patients. This is evidenced by the formation of the International Workshop on MS Comorbidities being sponsored by the International Advisory Committee on Clinical trials of the European Committee for Treatment and Research in MS (ECTRIMS) and the National MS Society (NMSS). This workshop is slated for late March, where a group of international MS researchers and clinicians will meet with the aims of better describing the types of comorbidities that commonly occur in MS patients, identifying gaps in the research and suggesting strategies for addressing these gaps. In this special issue of the Multiple Sclerosis Journal, Marrie and colleagues present six papers that provide a comprehensive review of the literature on the incidence and prevalence of a variety of comorbidities in MS. These papers provide a foundation for discussions at the upcoming MS Comorbidities workshop as well as providing the MS field with a compendium of the existing literature on the incidence and prevalence of comorbidities that occur in patients with MS. The authors reviewed over 7000 studies of comorbidities in MS that yielded 249 studies, from 1905 through 2012, which underwent detailed review and were then included in the six reported meta-analyses (details of the search strategy and study selection procedures are provided in the lead article1). There was great variability across studies in relation to the study population and study size, ascertainment methods for the comorbidities studied and statistical methods such as reporting of incidence/prevalence estimates by demographic

groups (age, sex and race) or standardised estimates to a common population. Additionally, there were only a few studies from Central/South America, Asia or Africa, severely limiting our understanding of comorbidity on those continents. In an effort to better describe the 249 included studies, the quality of each was graded on an 8-point scale.2 Given the time frame covered by the included studies and the limitations already noted, it is not surprising that only 32% of studies were graded as being of moderate to good quality (6 or greater). To further assess the reliability of deriving a pooled incidence/ prevalence estimate across studies, the I2 statistic was computed for only the population-based studies assessing specific comorbidity groupings (e.g., hypertension, depression, etc.). The I2 statistic provides an index of the proportion of the total variance in the pooled estimate that is due to between-study variability.3 An I2 of 30% or less would be considered mild heterogeneity, whereas an I2 of 50% or more would be deemed ‘substantial’. For most of the comorbidity groups analyzed, the I2 was 85% or greater confirming the marked variability, noted above, even when limited to the population-based studies. In light of the assessment of study quality, I2 and given the fact that frequently there were only a few studies contributing to the pooled estimate, we should proceed with caution when trying to draw conclusions about the incidence or prevalence of a given comorbidity. The use of Forest plots throughout the papers provides a relatively easy way to visually determine a range, based on the reported studies, within which the ‘true’ estimate likely falls.

Correspondence to: William J. Culpepper II Associate Director, Epidemiology & Outcomes, VHA Multiple Sclerosis Center of Excellence–East; Assistant Professor, Department of Neurology, University of Maryland School of Medicine, 10 North Greene Street, Mail Stop 151, 3D153, Baltimore, MD 21201, USA. [email protected] William J Culpepper II Department of Neurology, University of Maryland School of Medicine, Baltimore, USA

Despite these limitations there are some general conclusions that can be drawn from this body of work. First, the five most prevalent comorbidities in MS were: depression, anxiety, hypertension, hypercholesterolemia and chronic lung disease. Second, thyroid disease and psoriasis were the most prevalent comorbid autoimmune diseases. Third, the risk of meningiomas

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Multiple Sclerosis Journal  and urinary system cancers was greater than expected and pancreatic, ovarian, prostate and testicular cancers lower than expected compared to the general population. Fourth, several comorbid conditions were found to occur more frequently than previous research had suggested, such as stroke, heart disease, congestive heart failure, arthritis, inflammatory bowel disease/irritable bowel syndrome, seizure disorders, sleep disorders, bipolar disorder and alcohol abuse.

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While these studies may not enable us to derive a reliable estimate of the incidence and prevalence of the comorbidities assessed, they do suggest that there are specific comorbid conditions that occur often enough that clinicians need to be aware of this and ensure that MS patients are appropriately screened and treated. In a recent paper, Marrie et al.4 found that MS patients with one or more comorbidities had a two-fold higher all-cause hospitalization rate than MS patients without any comorbidity. Similarly, Marrie et al.5 have also shown that MS patients with vascular comorbidities any time during their disease course progressed to an EDSS of 6 on average 6 years sooner than MS patients who never had a vascular comorbidity. These are but two examples of why the MS field needs to better understand the impact of comorbidity on the health and well-being of MS patients, and suggests that routine screening for comorbidity should be part of standard MS care.

Conflict of interest None declared. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.

References 1.

Marrie RA, Cohen J, Stuve O, et al. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis. Mult Scler J 2015.

2.

Evans C, Beland S, Kulaga S, et al. Incidence and prevalence of multiple sclerosis in the Americas: a systematic review. Neuroepidemiol 2013; 40: 195–210.

3.

Higgins JPT and Thompson SG. Quantifying heterogeneity in a meta-analysis. Stats in Med 2002; 21: 1539–1558.

4.

Marrie RA, Elliott L, Marriott J, et al. Comorbidity increases the risk of hospitalizations in multiple sclerosis. Neurology 2015; 84: 350–358.

5.

Marrie RA, Rudick R, Horwitz R, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurol 2010; 74: 1041–1047.

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The incidence and prevalence of comorbidity in multiple sclerosis.

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