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

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.

Systematic review of mental health comorbidities in psoriatic arthritis.

OBJECTIVE: In this systematic review and meta-analysis of psoriatic arthritis (PsA) studies, we pooled data from existing literature to (1) estimate the prevalence of mental health disorders in PsA patients and (2) compare disease activity in PsA patients with and without these comorbidities. METHOD: We searched PubMED, Web of Science, Scopus, PsycINFO and the Cochrane Library using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Where possible, meta-analysis was performed using random effects model. Prevalence estimates were pooled according to the severity of mental health disorders. RESULTS: A total of 24 studies, amounting to 31,227 PsA patients, were included for review. Anxiety and depression were the only consistently reported mental health disorders, defined using a range of screening criteria/thresholds. Anxiety prevalence ranged from 4 to 61% with a pooled estimate of 33% (95%CI 17 to 53%) having at least mild anxiety and 21% (95%CI 14 to 29%) at least moderate. Depression prevalence ranged from 5 to 51%, with 20% (95%CI 8 to 35%) having at least mild and 14% (95%CI 8 to 21%) at least moderate. Only two studies compared disease activity according to the presence of mental health comorbidities; both reported higher disease activity and pain among those with comorbid anxiety and depression. CONCLUSIONS: Anxiety and depression are highly prevalent among PsA patients. Studies of other mental health disorders were scarce. More studies are needed on the impact of these comorbidities on disease activity and long-term outcomes.Key Points• One in three patients with psoriatic arthritis has at least mild anxiety, while 1 in 5 reported at least mild depression.• PsA patients with anxiety and/or depression reported greater disease activity.• More research is needed on other mental health comorbidities, particularly sleep, suicide/self-harm and substance misuse.

The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis.

Fibromyalgia (FM) is one of the most common conditions that rheumatologists encounter. It is characterised by chronic widespread pain, fatigue, sleep disturbances and impaired cognition. The prevalence of comorbid FM among populations with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are considerably higher than among the general population, with pooled prevalence estimates of 18-24% in RA, 14-16% in axSpA and 18% in PsA. Prevalence estimates should be interpreted with care as the criteria for FM have not been validated for use in patients with inflammatory arthritis. Comorbid FM appears to affect assessment of disease severity in these conditions, particularly patient-reported outcome measures, and may influence response to treatment. There is a need for better identification, classification and management of FM in the context of inflammatory rheumatic diseases.

Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis.

BACKGROUND: The impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA). METHODS: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights. RESULTS: A total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41). CONCLUSION: Baseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.

Comorbidity burden in axial spondyloarthritis: a cluster analysis.

OBJECTIVES: To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. METHODS: We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. RESULTS: We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1-6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI -0.37, -0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. CONCLUSION: Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity.

The prevalence of depression in axial spondyloarthritis and its association with disease activity: a systematic review and meta-analysis.

BACKGROUND: Depression is common among patients with axial spondyloarthritis (axSpA), but reports of its prevalence are highly variable. We performed a systematic review to (i) describe the prevalence of depression in axSpA, (ii) compare its prevalence between axSpA, ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) cohorts, and (iii) compare disease activity and functional impairment between those with and without depression. METHODS: We searched Medline, PubMed, Web of Science, PsycINFO, CINAHL Plus, the Cochrane library and conference abstracts of the European League Against Rheumatism, British Society for Rheumatology and American College of Rheumatology using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed using quality-effects model. RESULTS: Fifteen original articles and one abstract were included for analysis; 14 studies described AS cohorts and two nr-axSpA. Three screening criteria and one diagnostic criterion were used to define depression. Prevalence ranged from 11 to 64% depending on criteria and thresholds used. Pooled prevalence of at least moderate depression was 15% using the Hospital Anxiety and Depression Scale (HADS) threshold of ≥ 11. The prevalence of depression was similar between axSpA, AS and nr-axSpA cohorts. Patients with depression had significantly worse disease activity, including higher BASDAI by 1.4 units (95% CI 1.0 to 1.9), ASDAS by 0.5 units (95% CI 0.3 to 0.7) and ESR by 3.5 mm/h (95% CI 0.6 to 6.4). They also had greater functional impairment with higher BASFI and BASMI by 1.2 units (95% CI 0.6 to 1.8) and 0.6 units (95% CI 0.3 to 0.8), respectively. Mean age of each study cohort inversely correlated with depression prevalence. CONCLUSIONS: Depression is common among axSpA patients and is associated with more severe disease activity and functional impairment. Identifying and managing depression should form part of their holistic care. Further longitudinal studies are needed to explore the impact of depression on treatment outcomes and axSpA treatment on symptoms of depression.

Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS. Methods: Cochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results. Results: Forty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11-25.2% (13% pooled in AS only). In PsA the range was 9.6-27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores). Conclusion: FM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions.

Alcohol and disease activity in axial spondyloarthritis: a cross-sectional study.

The objective of this study was to explore associations between alcohol consumption and disease activity in axial spondyloarthritis (axSpA). We conducted a cross-sectional study of axSpA participants meeting the ASAS criteria. Associations between self-reported current alcohol use and disease activity (BASDAI, spinal pain, ASDAS), functional impairment (BASFI), and quality of life were explored using multivariable linear models, adjusting for age, gender, symptom duration, use of TNF inhibition therapy, smoking, deprivation, and anxiety and depression (A&D). Within alcohol drinkers, effect of increased alcohol intake (defined as > 14 units/week) was explored with moderate drinking (≤ 14 units/week) as reference. The study cohort comprised 229 axSpA patients and 76% were male with mean age 46.5 years (SD ± 13.8). Alcohol drinking was reported by 64%, with a median of 6 units per week among drinkers. Compared with non-drinkers, drinkers had lower BASDAI (ß = - 0.83; 95% CI - 1.49, - 0.17), ASDAS (ß = - 0.36; 95% CI - 0.66, - 0.05) and BASFI (ß = - 1.40; 95% CI - 2.12, - 0.68). These associations were in contrast to, and independent of, the detrimental effects of smoking, depression, and deprivation. Subgroup analysis in alcohol drinkers did not reveal significant associations between disease severity and increased alcohol intake. Stratified analyses by smoking revealed that in never-smokers without depression, alcohol was associated with greater reduction in disease activity: BASDAI (ß = - 1.69; 95% CI - 2.93, - 0.45), ASDAS (ß = - 0.60; 95% CI - 1.18, - 0.02). Favourable axSpA disease activity and function were observed in association with alcohol consumption in this cross-sectional study. Longitudinal study is required to explore whether this relationship is due to biological effects of alcohol on disease process or disease-associated behaviour modification.

The contribution of musculoskeletal disorders in multimorbidity: Implications for practice and policy.

People frequently live for many years with multiple chronic conditions (multimorbidity) that impair health outcomes and are expensive to manage. Multimorbidity has been shown to reduce quality of life and increase mortality. People with multimorbidity also rely more heavily on health and care services and have poorer work outcomes. Musculoskeletal disorders (MSDs) are ubiquitous in multimorbidity because of their high prevalence, shared risk factors, and shared pathogenic processes amongst other long-term conditions. Additionally, these conditions significantly contribute to the total impact of multimorbidity, having been shown to reduce quality of life, increase work disability, and increase treatment burden and healthcare costs. For people living with multimorbidity, MSDs could impair the ability to cope and maintain health and independence, leading to precipitous physical and social decline. Recognition, by health professionals, policymakers, non-profit organisations, and research funders, of the impact of musculoskeletal health in multimorbidity is essential when planning support for people living with multimorbidity.

Systematic review of association between vitamin D levels and susceptibility and disease activity of ankylosing spondylitis.

OBJECTIVES: Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some autoimmune conditions. There has been little focus on the potential immunomodulatory role of vitamin D in AS. This study systematically reviews the evidence for an association between vitamin D deficiency and disease susceptibility and severity in AS. METHODS: A systematic review was conducted using Medline, EMBASE, Web of Science and conference abstracts of the European League Against Rheumatism (2002-13), British Society for Rheumatology (1993-2013) and ACR (2006-13). RESULTS: Fifteen original articles and five conference abstracts met the criteria for inclusion. All were cross-sectional in design. Seven of 11 studies identified lower concentrations of 25-hydroxyvitamin D (25OHD) in AS patients compared with healthy controls. A significant inverse correlation between 25OHD and disease activity was observed in 5 of 11 studies. The majority of studies that failed to demonstrate significant findings used inappropriate statistical methods. CONCLUSION: Cross-sectional studies using appropriate statistical analyses have highlighted that AS is associated with lower vitamin D concentrations. Within groups of AS patients there is some evidence that low vitamin D concentrations are associated with higher disease activity. However, there are insufficient published data to support an immunomodulatory role for vitamin D in AS. Further study with a longitudinal design is required to understand whether optimizing vitamin D in AS has potential as a disease-modifying intervention.