References
The prevalence of comorbidity in rheumatoid arthritis: a systematic review and meta-analysis

Abstract
This systematic review and meta-analysis estimates the prevalence of common comorbid health disorders in adults with rheumatoid arthritis (RA). A multi-database search strategy was undertaken. Screening, data extraction and quality assessment were carried out by two independent reviewers. A meta-analysis and meta-regression were used to generate a pooled prevalence estimate and identify relevant moderators. After study selection, 33 studies (74633 participants) were included in the meta-analysis. Some 31 studies were judged to be of low risk of bias, and two studies were judged to be at moderate risk of bias. The three most common comorbidities in RA were anxiety disorders (62.1%, 95% Cl: 43.6%; 80.6%), hypertension (37.7%, 95% Cl: 29.2%; 46.2%) and depression (32.1%, 95% Cl: 21.6%; 42.7%). There was substantial statistically significant heterogeneity for all comorbidities (I2 ≥77%). Meta-regression identified that the covariate of mean age (unit increase) had a statistically significant effect on the prevalence of hypertension (+2.3%, 95% Cl: 0.4%; 4.2%), depression (−0.5%, 95% Cl: −0.6%; −0.4%) and cancer (0.5%, 95% Cl: 0.2%; 0.8%) in adults with RA. A country's income was identified to have a statistically significant effect on the prevalence of depression, with low-to moderate-income countries having 40% (95% Cl: 14.0%; 66.6%) higher prevalence than high-income countries. No studies consider health inequalities. It is concluded that comorbidities are prevalent among people with RA, particularly those associated with mental health and circulatory conditions. Provision of health services should reflect the importance of such multimorbidity and the consequences for quality and length of life.
Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease that primarily affects the synovial joints (Miao et al, 2013). It causes inflammation and thickening of the synovium, leading to pain and swelling, which can progress to erosion/damage to the cartilage and bone ends in the joint (Miao et al, 2013). As a progressive disease, it is associated with systemic complications (Firestein, 2003), socioeconomic costs (Merkesdal et al, 2005; Rkain et al, 2006) and consequences in all aspects of an individual's life (Eberhardt et al, 2007; Matcham et al, 2014). Despite improvements in the management of RA, it continues to be associated with increased morbidity, mortality and costs of care (Wolfe et al, 1994; Fautrel et al, 2007; Løppenthin et al, 2019). With more than 24 million people thought to have RA globally (Disease et al, 2016), it represents an often unrecognised challenge to health and social care services (Safiri et al, 2019). Although part of that challenge stems from the condition itself, RA is often accompanied by various comorbidities (additional condition(s) in the presence of a specific index condition of interest) that can affect different body systems (Gabriel, 2008; Espino-Lorenzo et al, 2013a; Jeong et al, 2017; Loppenthin et al, 2019). In addition to the specific effects of the comorbid condition, these may also aggravate the RA, which may cause functional decline, increase the costs of care and the person's risk of death (Gabriel and Michaud, 2009; Norton et al, 2013; Loppenthin et al, 2019).
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