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Objectives Epidemiological estimates of psoriatic arthritis (PsA) underpin the provision of healthcare, research, and the work of government, charities and patient organizations. Methodological problems impacting prior estimates include small sample sizes, incomplete case ascertainment, and representativeness. We developed a statistical modelling strategy to provide contemporary prevalence and incidence estimates of PsA from 1991 to 2020 in the UK. Methods Data from Clinical Practice Research Datalink (CPRD) were used to identify cases of PsA between 1st January 1991 and 31st December 2020. To optimize ascertainment, we identified cases of Definite PsA (≥1 Read code for PsA) and Probable PsA (satisfied a bespoke algorithm). Standardized annual rates were calculated using Bayesian multilevel regression with post-stratification to account for systematic differences between CPRD data and the UK population, based on age, sex, socioeconomic status and region of residence. Results A total of 26 293 recorded PsA cases (all definitions) were identified within the study window (77.9% Definite PsA). Between 1991 and 2020 the standardized prevalence of PsA increased twelve-fold from 0.03–0.37. The standardized incidence of PsA per 100 000 person years increased from 8.97 in 1991–15.08 in 2020, an almost 2-fold increase. Over time, rates were similar between the sexes, and across socioeconomic status. Rates were strongly associated with age, and consistently highest in Northern Ireland. Conclusion The prevalence and incidence of PsA recorded in primary care has increased over the last three decades. The modelling strategy presented can be used to provide contemporary prevalence estimates for musculoskeletal disease using routinely collected primary care data. [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]

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]

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 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]

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

Objectives To compare the prevalence and incidence of chronic co-morbidities in people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), and to determine whether the prevalent co-morbidities are associated with physical activity levels in people with iRMDs and in those without iRMDs. Methods Participants were recruited to the UK Biobank; a population-based cohort. Data were collected about demographics, physical activity, iRMDs (RA, PsA, AS, SLE) and other chronic conditions, including angina, myocardial infarction, stroke, hypertension, pulmonary disease, diabetes and depression. The standardized prevalence of co-morbidities in people with iRMDs was calculated. Cox regression was used to determine the relationship between the presence of an iRMD and an incident co-morbidity. The relationship between the presence (versus absence) of a (co-)morbidity and physical activity level (low, moderate, high) in people with iRMDs and in those without was assessed using multinomial logistic regression. Results A total of 488 991 participants were included. The estimated prevalence of each co-morbidity was increased in participants with an iRMD, compared with in those without, particularly for stroke in participants with SLE (standardized morbidity ratio (95% CI), 4.9 (3.6, 6.6). Compared with people with no iRMD and no morbidity, the odds ratios (95% CI) for moderate physical activity were decreased for: no iRMD and morbidity, 0.87 (0.85, 0.89); iRMD and no co-morbidity, 0.71 (0.64, 0.80); and iRMD and co-morbidity, 0.58 (0.54, 0.63). Conclusion Having a (co-)morbidity is associated with reduced physical activity in the general population, and to a greater extent in participants with an iRMD. Optimal management of both iRMDs and co-morbidities may help to reduce their impact on physical activity. [ABSTRACT FROM AUTHOR]

Objective: Potential targets for treat‐to‐target strategies in juvenile idiopathic arthritis are minimal disease activity (MDA) and clinically inactive disease (CID). We undertook this study to compare short‐ and long‐term outcomes following achievement of MDA and CID on the 10‐joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10) and following achievement of CID on Wallace et al's preliminary criteria. Methods: Children recruited to the Childhood Arthritis Prospective Study, a UK multicenter inception cohort, were selected if they were recruited prior to January 2011 and diagnosed as having oligoarthritis or rheumatoid factor–negative or –positive polyarthritis. One year following diagnosis, children were assessed for MDA on the cJADAS10 and for CID on both Wallace et al's preliminary criteria and the cJADAS10. Associations were tested between those disease states and functional ability, absence of joints with limited range of motion, psychosocial health, and pain at 1 year and annually to 5 years. Results: Of 832 children, 70% were female and the majority had oligoarthritis (68%). At 1 year, 21% had achieved CID according to both definitions, 7% according to Wallace et al's preliminary criteria alone, and 16% according to the cJADAS10 alone; 56% had not achieved CID. Only 10% of children in the entire cohort achieved MDA without also achieving CID. Achieving either early CID state was associated with a greater absence of joints with limited range of motion. However, only CID according to the cJADAS10 was associated with improved functional ability and psychosocial health. Achieving CID was superior to achieving MDA in terms of short‐ and long‐term pain and the absence of joints with limited range of motion. Conclusion: CID on the cJADAS10 may be preferable as a treatment target to CID on Wallace et al's preliminary criteria in terms of both feasibility of application and long‐term outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives. Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP. Methods. Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ≽3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time. Results. A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5. Conclusion. Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy. [ABSTRACT FROM AUTHOR]

Objectives. Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent.Methods. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients’ total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up.Results. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving.Conclusion. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention. [ABSTRACT FROM PUBLISHER]

Purpose: To assess sickness absence and transitions from employment for employees with arthritis compared with employees without arthritis over time., Methods: We use 10 waves of the UK Household Longitudinal Survey (2009-2019). The sample (n=38 928) comprises employees aged 50 years to state retirement age. Arthritis was self-reported and could refer to people with conditions under the umbrella term 'inflammatory arthritis' or osteoarthritis (hereafter 'arthritis'). Weighted random-effects multivariable linear probability models were estimated for two employment-related measures (1) sickness absence and (2) transitions from employment to: (a) unemployment; (b) long-term sick; (c) early retirement. These were regressed against a variable for arthritis and confounding factors (age, socioeconomic job classification, employing sector, year and additional health conditions). Additional analyses examined an interaction between the variable arthritis and these factors to test whether the effect of arthritis differs between these groups., Results: Employees reporting having arthritis were more likely to have sickness absence (1.35 percentage points greater rate (95% CI (0.92, 1.78)) and to transition to long-term sick (0.79 percentage points (0.46, 1.13)) and early retirement (0.58 percentage points (0.05, 1.11)). No effect was found for transitions to unemployment. There was limited evidence that the effects of arthritis vary for employees in different socioeconomic classifications., Conclusions: Employees living with arthritis have higher rates of sickness absence and greater rates of transitions from employment to long-term sick and early retirement. Further work could look at ways to quantify the implications for individuals, employers and the state and ways to alleviate the effects of living with arthritis on work participation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: As young people enter adulthood, the interchangeable use of child and adult outcome measures may inaccurately capture changes over time. This study aimed to use item response theory (IRT) to model a continuous score for functional ability that can be used no matter which questionnaire is completed., Methods: Adolescents (ages 11-17 years) in the UK Childhood Arthritis Prospective Study (CAPS) self-completed an adolescent Childhood Health Assessment Questionnaire (CHAQ) and a Health Assessment Questionnaire (HAQ). Their parents answered the proxy-completed CHAQ. Those children with at least 2 simultaneously completed questionnaires at initial presentation or 1 year were included. Psychometric properties of item responses within each questionnaire were tested using Mokken analyses to assess the applicability of IRT modeling. A previously developed IRT model from the Pharmachild-NL registry from The Netherlands was validated in CAPS participants. Agreement and correlations between IRT-scaled functional ability scores were tested using intraclass correlations and Wilcoxon's signed rank tests., Results: In 303 adolescents, the median age at diagnosis was 13 years, and 61% were female. CHAQ scores consistently exceeded HAQ scores. Mokken analyses demonstrated high scalability, monotonicity, and the fact that each questionnaire yielded reliable scores. There was little difference in item response characteristics between adolescents enrolled in CAPS and Pharmachild-NL (maximum item residual 0.08). Significant differences were no longer evident between IRT-scaled HAQ and CHAQ scores., Conclusion: IRT modeling allows the direct comparison of function scores regardless of different questionnaires being completed by different people over time. IRT modeling facilitates the ongoing assessment of function as adolescents transfer from pediatric clinics to adult services., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals Inc. on behalf of American College of Rheumatology.)

Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study.

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

Background: Methotrexate (MTX) remains the disease-modifying anti-rheumatic drug of first choice in rheumatoid arthritis (RA) but response varies. Predicting non-response to MTX could enable earlier access to alternative or additional medications and control of disease progression. We aimed to identify baseline predictors of non-response to MTX and combine these into a prediction algorithm., Methods: This study included patients recruited to the Rheumatoid Arthritis Medication Study (RAMS), a UK multi-centre prospective observational study of patients with RA or undifferentiated polyarthritis, commencing MTX for the first time. Non-response to MTX at 6 months was defined as "no response" using the European League Against Rheumatism (EULAR) response criteria, discontinuation of MTX due to inefficacy or starting biologic therapy. The association of baseline demographic, clinical and psychosocial predictors with non-response was assessed using logistic regression. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots., Results: Of 1050 patients, 449 (43%) were classified as non-responders. Independent multivariable predictors of MTX non-response (OR (95% CI)) were rheumatoid factor (RF) negativity (0.62 (0.45, 0.86) for RF positivity versus negativity), higher Health Assessment Questionnaire score (1.64 (1.25, 2.15)), higher tender joint count (1.06 (1.02, 1.10)), lower Disease Activity score in 28 joints (0.29 (0.23, 0.39)) and higher Hospital Anxiety and Depression Scale anxiety score (1.07 (1.03, 1.12)). The optimism-corrected AUC was 0.74., Conclusions: This is the first model for MTX non-response to be developed in a large contemporary study of patients commencing MTX in which demographic, clinical and psychosocial predictors were considered. Patient anxiety was a predictor of non-response and could be addressed at treatment commencement.

Background: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, approximately one quarter of patients discontinue MTX within 12 months. MTX failure, defined as MTX cessation or the addition of another anti-rheumatic drug, is usually due adverse event(s) and/or inefficacy. The aims of this study were to evaluate the rate and predictors of oral MTX failure., Methods: Subjects were recruited from the Norfolk Arthritis Register (NOAR), a primary care-based inception cohort of patients with early inflammatory polyarthritis (IP). Subjects were eligible if they commenced MTX as their first DMARD and were recruited between 2000 and 2008. Patient-reported reasons for MTX failure were recorded and categorised as adverse event, inefficacy or other. The addition of a second DMARD during the study period was categorised as failure due to inefficacy. Cox proportional hazards regression models were used to assess potential predictors of MTX failure, accounting for competing risks., Results: A total of 431 patients were eligible. The probability of patients remaining on MTX at 2 years was 82%. Competing risk analysis revealed that earlier MTX failure due to inefficacy was associated with rheumatoid factor (RF) positivity, younger age at symptom onset and higher baseline disease activity (DAS-28). MTX cessation due to an adverse event was less likely in the RF-positive cohort., Conclusions: RF-positive inflammatory polyarthritis patients who are younger with higher baseline disease activity have an increased risk of MTX failure due to inefficacy. Such patients may require combination therapy as a first-line treatment.