Exploring the validity of estimating EQ-5D and SF-6D utility values from the health assessment questionnaire in patients with inflammatory arthritis

<p>Abstract</p> <p>Background</p> <p>Utility scores are used to estimate Quality Adjusted Life Years (QALYs), applied in determining the cost-effectiveness of health care interventions. In studies where no preference based measures are collected, indirect methods have been developed to estimate utilities from clinical instruments. The aim of this study was to evaluate a published method of estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based) utility scores from the Health Assessment Questionnaire (HAQ) in patients with inflammatory arthritis.</p> <p>Methods</p> <p>Data were used from 3 cohorts of patients with: early inflammatory arthritis (<10 weeks duration); established (>5 years duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published method. Differences between predicted and observed EQ-5D and SF-6D scores were assessed using the paired t-test and linear regression.</p> <p>Results</p> <p>Predicted utility scores were generally higher than observed scores (range of differences: EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ-5D and SF-6D corresponded well with observed change in patients with established RA. Change in predicted SF-6D scores was, however, less than half of that in observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D scores underestimated change in cohorts of patients with more active disease.</p> <p>Conclusion</p> <p>Predicted utility scores overestimated baseline values but underestimated change. Predicting utility values from the HAQ will therefore likely underestimate the QALYs of interventions, particularly for patients with active disease. We recommend the inclusion of at least one preference based measure in future clinical studies.</p

Do associations between education and obesity vary depending on the measure of obesity used? A systematic literature review and meta-analysis

Background Consistent evidence suggests a relationship between lower educational attainment and total obesity defined using body mass index (BMI); however, a comparison of the relationships between educational attainment and total obesity (BMI ≥30 kg/m2) and central obesity (waist circumference (WC) > 102 cm for men and WC > 88 cm for women) has yet to be carried out. This systematic literature review (SLR) and meta-analyses aimed to understand whether i) the associations between education and obesity are different depending on the measures of obesity used (BMI and WC), and ii) to explore whether these relationships differ by gender and region. Methods Medline, Embase and Web of Science were searched to identify studies investigating the associations between education and total and central obesity among adults in the general population of countries in the Organisation for Economic Co-operation and Development (OECD). Meta-analyses and meta-regression were performed in a subset of comparable studies (n=36 studies; 724,992 participants). Results 86 eligible studies (78 cross-sectional and eight longitudinal) were identified. Among women, most studies reported an association between a lower education and total and central obesity. Among men, there was a weaker association between lower education and central than total obesity (OR central vs total obesity in men 0.79 (95% CI 0.60, 1.03)). The association between lower education and obesity was stronger in women compared with men (OR women vs men 1.66 (95% CI 1.32, 2.08)). The relationship between lower education and obesity was less strong in women from Northern than Southern Europe (OR Northern vs Southern Europe in women 0.37 (95% CI 0.27, 0.51)), but not among men. Conclusions Associations between education and obesity differ depending on whether total or central obesity is used among men, but not in women. These associations are stronger among women than men, particularly in Southern European countries

Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis:Results from the Norfolk Arthritis Register

Objectives: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years’ follow-up in a cohort of patients with inflammatory polyarthritis (IP).  Methods: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.  Results: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.  Conclusions: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA

Is the relationship between deprivation and outcomes in rheumatoid arthritis mediated by body mass index? A longitudinal cohort study

ObjectivesTo understand the relationships between deprivation and obesity with self-reported disability and disease activity in people with RA, and to determine whether BMI mediates the relationship between area-level deprivation and these outcomes.MethodsData came from the Rheumatoid Arthritis Medication Study (RAMS), a 1-year multicentre prospective observational cohort of people with RA recruited from rheumatology centres across England commencing MTX for the first time. A total of 1529 and 1626 people were included who had a baseline and at least one follow-up measurement at 6 or 12 months of HAQ-Disability Index (HAQ-DI) and DAS in 28 joints (DAS28), respectively. Linear mixed models estimated the associations of deprivation and obesity with repeated measures HAQ-DI and DAS28. Causal mediation analyses estimated the mediating effect of BMI on the relationship between deprivation and RA outcomes.ResultsHigher deprivation and obesity were associated with higher disability [adjusted regression coefficients highest vs lowest deprivation fifths 0.32 (95% CI 0.19, 0.45); obesity vs no obesity 0.13 (95% CI 0.06, 0.20)] and higher disease activity [adjusted regression coefficients highest vs lowest deprivation fifths 0.34 (95% CI 0.11, 0.58); obesity vs no obesity 0.17 (95% CI 0.04, 0.31)]. BMI mediated part of the association between higher deprivation and self-reported disability (14.24%) and DAS (17.26%).ConclusionsPeople with RA living in deprived areas have a higher burden of disease, which is partly mediated through obesity. Weight-loss strategies in RA could be better targeted towards those living in deprived areas

Does body mass index mediate the relationship between socioeconomic position and incident osteoarthritis?

Objectives: To investigate associations of socioeconomic position (SEP) and obesity with incident osteoarthritis (OA), and to examine whether body mass index (BMI) mediates the association between SEP and incident OA. Methods: Data came from the English Longitudinal Study of Ageing, a population-based cohort study of adults aged ≥50 years. The sample population included 9,281 people. Cox regression analyses were performed to investigate the associations between SEP (measured by education, occupation, income, wealth and deprivation) and obesity (BMI ≥30 kg/m2) at baseline and self-reported incident OA. The mediating effect of BMI on the relationship between SEP and incident OA were estimated using Structural Equation Models. Results: After a mean follow-up time of 7.8 years, 2,369 participants developed OA. Number of person-years included in the analysis was 65,456. Lower SEP was associated with higher rates of OA (for example, hazard ratio (HR) lowest vs highest education category 1.52 (95% confidence interval (CI) 1.30, 1.79)). Obesity compared with non-obesity was associated with increased rates of incident OA (HR 1.37 (95% CI 1.23, 1.52)). BMI mediated the relationship between a lower SEP and OA (β=0.005, p<0.001) and the direct effect was not significant (β=0.004, p=0.212). Conclusions: Strategies to reduce social inequalities and obesity prevalence may help to reduce OA risk

The association between lower socioeconomic position and functional limitations is partially mediated by obesity in older adults with symptomatic knee osteoarthritis: findings from the English Longitudinal Study of Ageing

Objective: To assess the longitudinal associations of socioeconomic position (SEP) with functional limitations and knee joint replacement surgery (JRS) in people with symptomatic knee osteoarthritis (OA), and whether body mass index (BMI) mediated these relationships. Methods: Data came from the English Longitudinal Study of Ageing, a national longitudinal panel study of adults aged ≥50 years. A total of 1,499 participants (62.3% female; mean age 66.5 (standard deviation (SD) 9.4) years; 47.4% obese) self-reporting an OA diagnosis and knee pain, with at least one BMI measurement were included. Mixed effect models estimated longitudinal associations of each SEP variable (education, occupation, income, wealth and deprivation index) and obesity (BMI ≥30.0 kg/m2) with repeated measures of functional limitations. Cox regression analyses estimated associations between SEP indicators and obesity at baseline and risk of knee JRS at follow-up. Structural equation modelling estimated any mediating effects of BMI on these relationships. Results: Lower SEP and obesity at baseline were associated with increased odds of functional limitations in people with knee OA (e.g. difficulty walking 100 yards: no qualification vs degree adjOR 4.33 (95% CI 2.20, 8.55) and obesity vs no obesity adjOR 3.06 (95% CI 2.14, 4.37); similar associations were found for the other SEP indicators). A small proportion of the association between lower SEP and functional limitations could be explained by BMI (6.2–12.5%). Those with lower income, lower wealth and higher deprivation were less likely to have knee JRS (e.g. adjHR most vs least deprived 0.37 (95% CI 0.19, 0.73)); however, no clear association was found for education and occupation. Obesity was associated with increased hazards of having knee JRS (adjHR 1.87 (95% CI 1.32, 2.66)). As the direction of the associations for SEP and obesity with knee JRS were in opposite directions, no mediation analyses were performed. Conclusions: Lower SEP was associated with increased odds of functional limitations but lower hazards of knee JRS among people with knee OA, potentially indicating underutilisation of JRS in those with lower SEP. Obesity partially mediated the relationship between lower SEP and increased odds of functional limitations, suggesting adiposity as a potential interventional target

Identification of cell‐specific differential DNA methylation associated with methotrexate treatment response in rheumatoid arthritis

ObjectiveWe undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment.MethodsPatients included in this study were from the Rheumatoid Arthritis Medication Study (n&nbsp;=&nbsp;66) and the University of California San Francisco Rheumatoid Arthritis study (n&nbsp;=&nbsp;11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software.ResultsWe found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.ConclusionWe identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells