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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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA)., Methods: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN])., Results: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (β = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (β = 0.24 [95% CI 0.14, 0.34]), less exercise (β = 0.17 [95% CI 0.09-0.25]), and less education (β = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN., Conclusion: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: A European League Against Rheumatism taskforce was convened to review the literature and develop recommendations on lifestyle behaviours for rheumatic and musculoskeletal diseases (RMDs)., Methods: Six lifestyle exposures (exercise, diet, weight, alcohol, smoking, work participation) and seven RMDs (osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, gout) were considered. The taskforce included health professionals in rheumatology, geriatricians, epidemiologists, public health experts, people with RMDs and exposure domain experts. Systematic reviews were conducted to gather available evidence, from which recommendations were developed., Results: Five overarching principles and 18 specific recommendations were defined based on available evidence. The overarching principles define the importance of a healthy lifestyle, how lifestyle modifications should be implemented, and their role in relation to medical treatments. Exercise recommendations highlight the safety and benefits of exercise on pain and disability, particularly among people with osteoarthritis and axial spondyloarthritis. The diet recommendations emphasise the importance of a healthy, balanced diet for people with RMDs. People with RMDs and health professionals should work together to achieve and maintain a healthy weight. Small amounts of alcohol are unlikely to negatively affect the outcomes of people with RMDs, although people with rheumatoid arthritis and gout may be at risk of flares after moderate alcohol consumption. Smokers should be supported to quit. Work participation may have benefits on RMD outcomes and should be discussed in consultations., Conclusions: These recommendations cover a range of lifestyle behaviours and can guide shared decision making between people with RMDs and health professionals when developing and monitoring treatment plans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed., Methods: Systematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage)., Results: In total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression., Conclusion: The current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Rheumatoid arthritis (RA) is associated with pain, disability and increased risk of developing comorbidities and premature mortality. While these poor outcomes have improved in line with advances in the treatment of RA, they still persist to some degree today. Physical activity and smoking are two areas of patients' lives where changes may have a substantial impact on the poor outcomes associated with RA. Physical activity in RA has been well studied, with many randomised trials indicating the benefits of physical activity on pain and disability. A number of observational studies have assessed the impact of smoking on RA, also indicating the benefits of quitting smoking on RA-related outcomes, but with less consistent findings, potentially due to epidemiological challenges (e.g. collider bias, recall bias). There are also a number of barriers preventing patients making these positive lifestyle changes, such as lack of time and motivation, lack of knowledge and advice, as well as disease-specific barriers, such as pain and fatigue., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: United Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA., Methods: The study included biologic-naïve patients receiving csDMARDs only with MDA (3.2

Objective: To assess baseline predictors of long-term functional disability in patients with inflammatory arthritis (IA)., Methods: We conducted a systematic review of the literature from 1990 to 2017 using MEDLINE and EMBASE. Studies were included if (i) they were prospective observational studies, (ii) all patients had IA with symptom duration ≤2 years at baseline, (iii) follow-up was at least 5 years, and (iv) baseline predictors of HAQ score at long-term follow-up (i.e., ≥5 years following baseline) were assessed. Information on the included studies and estimates of the association between baseline variables and long-term HAQ scores were extracted from the full manuscripts., Results: Of 1037 abstracts identified by the search strategy, 37 met the inclusion/exclusion criteria and were included in the review. Older age at baseline and female gender were reported to be associated with higher long-term HAQ scores in the majority of studies assessing these relationships, as were higher baseline HAQ and greater pain scores (total patients included in analyses reporting significant associations/total number of patients analysed: age 9.8k/10.7k (91.6%); gender 9.9k/11.3k (87.4%); HAQ 4.0k/4.0k (99.0%); pain 2.8k/2.9k (93.6%)). Tender joint count, erythrocyte sedimentation rate (ESR) and DAS28 were also reported to predict long-term HAQ score; other disease activity measures were less consistent (tender joints 2.1k/2.5k (84.5%); erythrocyte sedimentation rate 1.6k/2.2k (72.3%); DAS28 888/1.1k (79.2%); swollen joints 684/2.6k (26.6%); C-reactive protein 279/510 (54.7%)). Rheumatoid factor (RF) and erosions were not useful predictors (RF 546/4.6k (11.9%); erosions 191/2.7k (7.0%)), whereas the results for anti-citrullinated protein antibody positivity were equivocal (ACPA 2.0k/3.8k (52.9%))., Conclusions: Baseline age, gender, HAQ and pain scores are associated with long-term disability and knowledge of these may aid the assessment of prognosis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years., Methods: Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression., Results: Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]., Conclusion: HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up., Methods: Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring., Results: This study included 602 patients with RA (median age 56 years [interquartile range 44-68 years]; 65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3 swollen joints and 3-6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow-up period (β = 0.03, 95% confidence interval [95% CI] -0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17])., Conclusion: The results of this study indicate the importance of early treatment with regard to the long-term outcomes in patients with RA., (© 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)