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Objective: The aims were to validate linguistically British‐English versions of the Perceived Workplace Support Scale (PWSS), Work Accommodations, Benefits, Policies and Practices Scale (WABPPS), and Work Transitions Index (WTI) in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), osteoarthritis (OA) and fibromyalgia (FM). Methods: The three scales were adapted into British‐English and reviewed by an expert panel prior to cognitive debriefing interviews. Participants completed postal questionnaires. Construct validity for the PWSS was assessed using Rasch analysis. Concurrent validity included testing between the three scales and work, job strain and work‐life balance scales. Two weeks later, participants were mailed a second questionnaire to measure test‐retest reliability. Results: The questionnaire was completed by 831 employed participants: 68% women, 53.50 (SD 8.9) years of age, with condition duration 7.70 (SD 8.00) years. The PWSS satisfied Rasch model requirements. Concurrent validity was mostly as hypothesised, that is, weak to moderate negative correlations for the PWSS (rs = 0.07 to −0.61), and weak to moderate positive correlations for the WABPPS and WTI (rs = 0.20–0.52). Some correlations were stronger, mostly in axSpA. Internal consistency (Cronbach's alpha) for all three scales was consistent with group use in all conditions. Test‐retest reliability was generally excellent, with intraclass coefficients (2,1) of 0.80–0.93 for the three scales in the four conditions. Discussion: Reliable, valid versions of the British‐English PWSS, WABPPS, and WTI are now available for use in research, organisational level studies and vocational rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: The aims were to validate linguistically British‐English versions of the Long‐Term Conditions Job Strain Scale (LTCJSS), Long‐Term Conditions Work Spillover Scale (LTCWSS) and Work‐Health‐Personal Life Perceptions Scale (WHPLPS) in rheumatoid arthritis, axial spondyloarthritis, osteoarthritis and fibromyalgia (FM). Methods: The three scales were forward translated and reviewed by an expert panel prior to cognitive debriefing interviews. Participants completed a postal questionnaire. Construct validity was assessed using Rasch analysis. Concurrent validity included testing between the three scales and work (e.g., Workplace Activity Limitations Scale [WALS]) and condition‐specific health scales. Two weeks later, participants were mailed a second questionnaire to measure test‐retest reliability. Results: The questionnaire was completed by 831 employed participants: 68% women, 53.5 (SD 8.9) years of age, with condition duration 7.7 (SD 8.0) years. The LTCJSS, LTCWSS and WHPLPS Parts 1 and 2 satisfied Rasch model requirements, but Part 3 did not. A Rasch transformation scale and Reference Metric equating scales with the WALS were created. Concurrent validity was generally good (rs = 0.41–0.85) for the three scales, except the WHPLPS Part 3. Internal consistency (Person Separation Index values) was consistent with group use in all conditions, and individual use except for the LTCWSS and WHPLSP Parts 1 and 2 in FM. Test‐retest reliability was excellent, with intraclass coefficients (2,1) of 0.80–0.96 for the three scales in the four conditions. Discussion: Reliable, valid versions of the British‐English LTCJSS, LTCWSS and WHPLPS Parts 1 and 2 are now available for use in the UK. [ABSTRACT FROM AUTHOR]

Objective: We 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. Methods: Patients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 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. Results: We 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. Conclusion: We 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. [ABSTRACT FROM AUTHOR]

Objectives To 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. Methods Data 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. Results Higher 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%). Conclusions People 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. [ABSTRACT FROM AUTHOR]

Hepatotoxicity is a serious adverse drug reaction related to methotrexate (MTX). However, the cause of drug‐induced liver injury (DILI) is still unclear and unpredictable. Genetic risk factors may predispose for MTX‐DILI. Therefore, we conducted a nested case‐control genome‐wide association study to explore genetic risk factors associated with MTX‐DILI. Seven international groups contributed blood samples and data of patients with rheumatoid arthritis who used MTX. MTX‐DILI was defined as an alanine aminotransferase (ALT) level of at least three times the upper limit of normal (ULN), to increase contrast controls ALT levels did not raise above two times the ULN. Per study site, control subjects and patients with MTX‐DILI (ratio 3:1) were matched for age, gender, and duration of MTX use. Patients were genotyped using Illumina GSA MD‐24v1‐0 and data were imputed using the 1000 Genomes reference panel. Single‐nucleotide polymorphisms (SNPs) were analyzed using an additive genetic model, corrected for sex, country, and age. A P‐value of ≤ 5 × 10−8 was considered significant, whereas a P‐value of ≤ 5 × 10−6 was considered suggestive. A total of 108 MTX‐DILI cases and 311 controls were included for association analysis. None of the SNPs were significantly associated with MTX‐DILI. However, we found seven suggestive genetic variants associated with MTX‐DILI (P‐values 7.43 × 10−8 to 4.86 × 10−6). Of those, five SNPs were in the intronic protein‐coding regions of FTCDNL1, BCOR, FGF14, RBMS3, and PFDN4/DOK5. Investigation of candidates SPATA9 (rs72783407), PLCG2 (rs60427389), RAVER2 (rs72675408), JAK1 (rs72675451), PTPN2 (rs2476601), MTHFR C677T (rs1801133), and into the HLA region did not show significant findings. No genetic variants associated with MTX‐DILI were found, whereas suggestive SNPs need further investigation. [ABSTRACT FROM AUTHOR]

Objectives To examine associations between PsA and psoriasis vs lifestyle factors and comorbidities by triangulating observational and genetic evidence. Methods We analysed cross-sectional data from the UK Biobank (1836 PsA, 8995 psoriasis, 36 000 controls) to describe the association between psoriatic disease and lifestyle factors (including BMI and smoking) and 15 comorbidities [including diabetes and coronary artery disease (CAD)] using logistic models adjusted for age, sex and lifestyle factors. We applied bidirectional Mendelian randomization (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757 601 for comorbidities) to examine causal direction, using the inverse-variance weighted method. Results BMI was cross-sectionally associated with risk of PsA (OR 1.31 per 5 kg/m2 increase; 95% CI 1.26, 1.37) and psoriasis (OR 1.23; 1.20, 1.26), with consistent MR estimates (PsA OR 1.38; 1.14, 1.67; psoriasis OR 1.36; 1.18, 1.58). In both designs, smoking was more strongly associated with psoriasis than PsA. PsA and psoriasis were cross-sectionally associated with diabetes (OR 1.35 and 1.39, respectively) and CAD (OR 1.56 and 1.38, respective). Genetically predicted glycated haemoglobin (surrogate for diabetes) increased PsA risk (OR 1.18 per 6.7 mmol/mol increase; 1.02, 1.36) but not psoriasis. Genetic liability to PsA (OR 1.05; 1.003, 1.09) and psoriasis (OR 1.03; 1.001, 1.06) were associated with increased risk of CAD. Conclusion Observational and genetic evidence converge to suggest that BMI and glycaemic control are associated with increased psoriatic disease risk, while psoriatic disease is associated with increased CAD risk. Further research is needed to understand the mechanism of these associations. [ABSTRACT FROM AUTHOR]

Objectives The aims were to validate a British English version of the Workplace Activity Limitations Scale (WALS) linguistically, then test this psychometrically in RA, axial spondyloarthritis (axSpA), OA and FM. Methods The WALS was forward translated, reviewed by an expert panel, and cognitive debriefing interviews were conducted. Participants completed a postal questionnaire booklet. Construct (structural) validity was examined by fit to the Rasch measurement model. Concurrent validity included testing between the WALS and the Work Limitations Questionnaire-25 (WLQ-25). Two weeks later, participants were mailed a second questionnaire booklet for test–retest reliability. Results Minor wording changes were made to the WALS, then 831 employed participants completed questionnaires: 267 men and 564 women; 53.5 (s. d. 8.9) years of age; with condition duration 7.7 (s. d. 8.0) years. The WALS satisfied Rasch model requirements, and a WALS Rasch transformation table was created. Concurrent validity was strong with the WLQ-25 (RA r s = 0.78; axSpA r s = 0.83; OA r s = 0.63; FM r s = 0.64). Internal consistency was consistent with group use (α = 0.80–0.87). Test–retest reliability was excellent, with intraclass correlation coefficient (2,1) at ≥0.90. Conclusion A reliable, valid British English version of the WALS is now available for use in the UK. [ABSTRACT FROM AUTHOR]

Objectives Uncertainty regarding the risk of coronavirus disease 2019 (COVID-19), its complications and the safety of immunosuppressive therapies may drive anxiety among adults and parents of children and young people (CYP) with rheumatic diseases. This study explored trajectories of COVID-related anxiety in adults and parents of CYP with rheumatic diseases. Methods Adults and parents of CYP participating in the international COVID-19 European Patient Registry were included in the current study if they had enrolled in the 4 weeks following 24 March 2020. COVID-related anxiety scores (0–10) were collected weekly for up to 28 weeks. Group-based trajectory models explored COVID-related anxiety clusters in adult and parent populations, with optimal models chosen based on model fit, parsimony and clinical plausibility. Demographic, clinical and COVID-19 mitigation behaviours were compared between identified clusters using univariable statistics. Results In 498 parents of CYP and 2640 adults, four common trajectory groups of COVID-related anxiety were identified in each cohort: persistent extreme anxiety (32% and 17%), persistent high anxiety (43% and 41%), improving high anxiety (25% and 32%) and improving moderate anxiety (11% and 10%), respectively. Few characteristics distinguished the clusters in the parent cohort. Higher and more persistent anxiety clusters in the adult cohort were associated with higher levels of respiratory comorbidities, use of immunosuppressive therapies, older age and greater self-isolation. Conclusions COVID-19-related anxiety in the rheumatic disease community was high and persistent during the COVID-19 pandemic, with four common patterns identified. In the adult cohort, higher COVID-related anxiety was related to perceived risk factors for COVID-19 morbidity and mortality. [ABSTRACT FROM AUTHOR]

The article discusses the Myositis Physical Activity Device (MyoPAD) Study which recruited adults with idiopathic inflammatory myopathy (IIM) via the specialist neuromuscular clinic at Salford Royal Hospital in England. Topics include participants of the study, the occurrence of patient-reported IIM flares alongside work absenteeism and reduced work productivity, and importance of adequate medical therapy and disease control to minimising disease flares.

Objective: To determine the association between osteoarthritis (OA), rheumatoid arthritis (RA), and frailty and to determine whether comorbidities interact with OA and RA to further increase the likelihood of frailty. Methods: Participants of the UK Biobank age 40–69 years at baseline were included. Demographic, lifestyle, and clinical data were collected at baseline and follow‐up in a subset. Frailty was assessed using a frailty index (FI) (continuous) and a modified frailty phenotype (robust, pre‐frail, frail). The association between RA and OA and frailty at baseline and follow‐up was assessed using multiple regression models. We looked at whether comorbidities, including cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, and depression interacted additively with OA and RA to increase the likelihood of frailty. Results: In total, 457,561 participants contributed data. Those with (versus without) RA (n = 4,894) and OA (n = 35,884), respectively, were more likely to be frail (adjusted relative risk ratio 10.7 [95% confidence interval (95% CI) 9.7, 11.7] and 3.4 [95% CI 3.3, 3.6]) and were more likely to have a higher FI at baseline. There was evidence of additive interaction between RA, OA, and common comorbidities increasing the occurrence of prevalent frailty. Among 25,163 participants included in longitudinal analysis, patients with RA (n = 202) and OA (n = 1,811) at baseline had an increased adjusted frailty incidence rate ratio (2.8 [95% CI 1.7, 4.6] and 1.7 [95% CI 1.3, 2.1], respectively) and also a higher FI during follow‐up. Conclusion: Individuals with RA and OA are more likely to have, or develop, frailty. Common comorbidities interact with OA and RA to further increase the likelihood of frailty. [ABSTRACT FROM AUTHOR]

Background No reliable biomarkers to predict response to TNF inhibitors (TNFi) in RA patients currently exist. The aims of this study were to replicate changes in gene co-expression modules that were previously reported in response to TNFi therapy in RA; to test if changes in module expression are specific to TNFi therapy; and to determine whether module expression transitions towards a disease-free state in responding patients. Method Published transcriptomic data from the whole blood of disease-free controls (n  = 10) and RA patients, treated with the TNFi adalimumab (n  = 70) or methotrexate (n  = 85), were studied. Treatment response was assessed using the EULAR response criteria following 3 or 6 months of treatment. Change in transcript expression between pre- and post-treatment was recorded for previously defined modules. Linear mixed models tested whether modular expression after treatment transitioned towards a disease-free state. Results For 25 of the 27 modules, change in expression between pre- and post-treatment in the adalimumab cohort replicated published findings. Of these 25 modules, six transitioned towards a disease-free state by 3 months (P   <  0.05), irrespective of clinical response. One module (M3.2), related to inflammation and TNF biology, significantly correlated with response to adalimumab. Similar patterns of modular expression, with reduced magnitude, were observed in the methotrexate cohort. Conclusion This study provides independent validation of changes in module expression in response to therapy in RA. However, these effects are not specific to TNFi. Further studies are required to determine whether specific modules could assist molecular classification of therapeutic response. [ABSTRACT FROM AUTHOR]

Objectives To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. Methods Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. Results This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. Conclusion Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function. [ABSTRACT FROM AUTHOR]

Objectives To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX. Methods Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥18 years with physician diagnosed RA and symptom duration ≤2 years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at 6- and 12-month follow-up visits. The period prevalence rates of AEs are reported for 0–6 months, 6–12 months and 0–12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression. Results A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematological AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological) and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated glomerular filtration rate and alcohol consumption were associated with less reporting of haematological AEs. Conclusions AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AE occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment. [ABSTRACT FROM AUTHOR]

Objectives To describe how many people with RA reduce their baseline physical activity level over the first year of MTX treatment, and which factors predict this. Methods Data came from the Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of people with early RA starting MTX. Participants reported demographics and completed questionnaires at baseline, and 6 and 12 months, including reporting the number of days per week they performed ≥20 min of physical activity, coded as none, low (1–3 days) or high (4–7 days). The physical activity levels of participants over 12 months are described. Predictors of stopping physical activity were assessed using multivariable logistic regression. Results In total, 1468 participants were included [median (interquartile range) age 60 (50, 69) years; 957 (65.2%) women]. At baseline, the physical activity levels of the people with RA were: none = 408 (27.8%), low = 518 (35.3%) and high = 542 (36.9%). Eighty percent of participants maintained some physical activity or began physical activity between assessments (baseline to 6 months = 79.3%, 6 months to 12 months = 80.7%). In total, 24.1% of participants reduced physical activity and 11.3% of participants stopped performing physical activity between baseline and 6 months (6 months to 12 months: 22.6% and 10.2%, respectively). Baseline smoking, higher disability and greater socioeconomic deprivation were associated with stopping physical activity. Conclusion Many people with early RA were not performing physical activity when starting MTX, or stopped performing physical activity over the first year of treatment. These people may require interventions to stay active. These interventions need to be mindful of socioeconomic barriers to physical activity participation. [ABSTRACT FROM AUTHOR]

Objectives This systematic review aims to summarize rates of adverse events (AEs) in patients with RA or inflammatory arthritis starting MTX as monotherapy or in combination with other csDMARDs, and to identify reported predictors of AEs. Methods Three databases were searched for studies reporting AEs in MTX-naïve patients with RA. Randomized controlled trials (RCTs) and observational cohort studies were included. Prevalence rates of AEs were pooled using random effects meta-analysis, stratified by study design. Results Forty-six articles (34 RCTs and 12 observational studies) were identified. The pooled prevalence of total AEs was 80.1% in RCTs (95% CI: 73.5, 85.9), compared with 23.1% in observational studies (95% CI: 12.3, 36.0). The pooled prevalence of serious AEs was 9.5% in RCTs (95% CI: 7.4, 11.7), and 2.1% in observational studies (95% CI: 1.0, 3.4). MTX discontinuation due to AEs was higher in observational studies (15.5%, 95% CI: 9.6, 22.3) compared with RCTs (6.7%, 95% CI: 4.7, 8.9). Gastrointestinal events were the most commonly reported AEs (pooled prevalence: 32.7%, 95% CI: 18.5, 48.7). Five studies examined predictors of AEs. RF status, BMI and HAQ score were associated with MTX discontinuation due to AEs; ACPA negativity, smoking and elevated creatinine were associated with increased risk of elevated liver enzymes. Conclusion The review provides an up-to-date overview of the prevalence of AEs associated with MTX in patients with RA. The findings should be communicated to patients to help them make informed choices prior to commencing MTX. [ABSTRACT FROM AUTHOR]

Background: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.Objectives: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.Methods: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.Results: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).Conclusion: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP. [ABSTRACT FROM AUTHOR]

Objectives To describe the illness perceptions of patients with RA over the first year of MTX treatment, and the association between illness perceptions and outcomes. Methods Data came from the Rheumatoid Arthritis Medication Study (RAMS), a UK multicentre cohort study of RA patients starting MTX for the first time. Patients were assessed at baseline, and at 6 and 12 months. Patients completed the Brief Illness Perception Questionnaire (B-IPQ) at each assessment, as well as other patient-reported outcomes (PROs). The inflammation score (2-component DAS28) was calculated. Subgroups of patients with similar trajectories across the eight (B-IPQ) items were identified using a latent class growth model. Predictors of group membership were identified using multinomial logistic regression. Associations between subgroups and PROs over follow-up were assessed using linear mixed models. Results Three subgroups were identified in the analysis population (N  = 1087): Positive illness perceptions (N  = 322), Negative illness perceptions (N  = 534) and Improvers (N  = 231) who switched from negative to positive illness perceptions over follow-up. Baseline disability was associated with group membership [Positive vs Negative: relative risk ratio (RRR) 0.37, 95% CI: 0.25, 0.54; Improvers vs Negative: RRR 0.60, 95% CI: 0.43, 0.83], as were other PROs (pain, fatigue, anxiety, depression). The Negative group had worse disability, pain and fatigue over follow-up compared with the other groups, controlling for inflammation. Conclusion Negative illness perceptions are associated with poor PROs over time. The Improvers subgroup illustrated that illness perceptions can change in RA. Illness perceptions represent a potential therapeutic target that should be assessed using randomized trials. [ABSTRACT FROM AUTHOR]

Objectives Work is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics. Methods Patients aged 18–65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated. Results A total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts. Conclusion Patients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation. [ABSTRACT FROM AUTHOR]

Objectives To describe outcomes of patients with early RA in a patient acceptable symptom state (PASS) at treatment initiation and to identify clusters of symptoms associated with poor outcomes. Methods Data came from the Rheumatoid Arthritis Medication Study, a UK multicentre cohort study of RA patients starting MTX. The HAQ, DAS28 and other patient-reported outcome measures (PROMs) were collected at baseline, and at 6 and 12 months. Patients answering yes to the question 'Is your current condition satisfactory, when you take your general functioning and your current pain into consideration?' were defined as PASS; patients answering no were defined as N-PASS. Symptom clusters in the baseline PASS group were identified using K-medians cluster analysis. Outcomes of baseline PASS vs N-PASS patients and each cluster are compared using random effects models. Results Of 1127 patients, 572 (50.8%) reported being in PASS at baseline. Over one year, baseline PASS patients had lower DAS28 (mean difference = −0.71, 95% CI −0.83, −0.59) and HAQ scores (mean difference = −0.48, 95% CI −0.56, −0.41) compared with N-PASS patients. Within the baseline PASS group, we identified six symptom clusters. Clusters characterized by high disease activity and high PROMs, or moderate disease activity and high PROMs, had the worst outcomes compared with the other clusters. Conclusion Despite reporting their condition as 'satisfactory', early RA patients with high PROM scores are less likely to respond to therapy. This group may require increased vigilance to optimize outcomes. [ABSTRACT FROM AUTHOR]

Objective: In pediatric research, investigators rely on proxy reports of outcome, such as the proxy-completed Childhood Health Assessment Questionnaire (C-HAQ), to assess function in juvenile idiopathic arthritis (JIA). As children mature, they may self-complete the adult HAQ or the unvalidated adolescent-specific C-HAQ. It is unclear how these measures compare and whether they are directly interchangeable. The present study was undertaken to compare agreement between the proxy-completed C-HAQ, adolescent-specific C-HAQ, and the HAQ at initial presentation to pediatric rheumatologic care and 1 year following the first presentation in adolescents with JIA.Methods: Adolescents ages 11-17 years participating in the Childhood Arthritis Prospective Study (CAPS), a UK multicenter inception cohort, were included. In a CAPS substudy, adolescents self-completed the adolescent-specific C-HAQ and the HAQ, and proxies simultaneously completed the proxy-completed C-HAQ at baseline and 1 year. Correlation and agreement between scores were assessed at baseline. Agreement and ability to similarly classify clinically important changes over time were assessed at 1 year following initial presentation to rheumatologic care.Results: A total of 107 adolescents (adolescent-specific C-HAQ and HAQ) or their proxies (proxy-completed C-HAQ) had completed all 3 measures at baseline. Median age at diagnosis was 13 years, and 61% were female. Although the 3 scores demonstrated strong correlations (r > 0.8), they were not completely interchangeable, with agreement ranging between 70% and 80%. There was similar agreement between the changes in scores between baseline and 1 year. Using proxy-completed C-HAQ minimum clinically important cutoffs, the adolescent-specific C-HAQ and the HAQ similarly classified 80% to 90% of adolescents as having improved or worsened.Conclusion: While there is relatively high agreement and similar classification of change between HAQ and the 2 C-HAQ scores, these are not completely interchangeable. This impacts the comparison of function when measured in different ways over the lifespan. [ABSTRACT FROM AUTHOR]

Objective In order to develop interventions to optimize MTX use for the treatment of RA we evaluated the rate of, reasons for and predictors of MTX non-adherence during the first 6 months of therapy. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a prospective multicentre cohort study of incident MTX users in the UK. Prior to MTX commencement demographic, clinical and psychological data were collected. A weekly patient-completed diary recorded MTX dose, possible side effects and adherence over 26 weeks. The number of non-adherent weeks was calculated. Potential baseline predictors of ever non-adherence (⩾1 week non-adherent) during the first 6 months of MTX therapy were identified using logistic regression analyses. Results 606 patients with RA were included; 69% female, mean (s.d.) age 60 (13) years and DAS28 score 4.2 (1.2). Over the first 6 months following MTX initiation, 158 (26%) patients were ever non-adherent (71% intentional, 19% non-intentional, 10% unexplained) and mean (s.d.) number of non-adherent weeks was 2.5 (2.1). Multivariable predictors of ever non-adherence included DAS28 [odds ratios (OR) 1.1, 95% CI 1.0, 1.4], fatigue (OR 1.1, 95% CI 1.0, 1.2 per cm), ⩾2 comorbidities vs no comorbidities (OR 1.9, 95% CI 1.1, 3.5) and high medication concerns despite perceived need (OR 1.1, 95% CI 1.0, 1.1 per unit decrease in need/concern differential). Conclusion This is the largest study evaluating early intentional and non-intentional non-adherence to MTX, which has identified that patient beliefs and multi-morbidity strongly link with non-adherence. These findings can direct the design of and provide potential targets for interventions to improve patient adherence. [ABSTRACT FROM AUTHOR]