How to develop, validate, and update clinical prediction models using multinomial logistic regression.

OBJECTIVES: Multicategory prediction models (MPMs) can be used in healthcare when the primary outcome of interest has more than two categories. The application of MPMs is scarce, possibly due to added methodological complexities compared to binary outcome models. We provide a guide of how to develop, validate, and update clinical prediction models based on multinomial logistic regression. STUDY DESIGN AND SETTING: We present guidance and recommendations based on recent methodological literature, illustrated by a previously developed and validated MPM for treatment outcomes in rheumatoid arthritis. Prediction models using multinomial logistic regression can be developed for nominal outcomes, but also for ordinal outcomes. This article is intended to supplement existing general guidance on prediction model research. RESULTS: This guide is split into three parts: 1) Outcome definition and variable selection, 2) Model development, and 3) Model evaluation (including performance assessment, internal and external validation, and model recalibration). We outline how to evaluate and interpret the predictive performance of MPMs. R code is provided. CONCLUSIONS: We recommend the application of MPMs in clinical settings where the prediction of a multicategory outcome is of interest. Future methodological research could focus on MPM-specific considerations for variable selection and sample size criteria for external validation.

Developing and externally validating multinomial prediction models for methotrexate treatment outcomes in patients with rheumatoid arthritis: results from an international collaboration.

OBJECTIVES: In rheumatology, there is a clinical need to identify patients at high risk (>50%) of not responding to the first-line therapy methotrexate (MTX) due to lack of disease control or discontinuation due to adverse events (AEs). Despite this need, previous prediction models in this context are at high risk of bias and ignore AEs. Our objectives were to (i) develop a multinomial model for outcomes of low disease activity and discontinuing due to AEs 6 months after starting MTX, (ii) update prognosis 3-month following treatment initiation, and (iii) externally validate these models. STUDY DESIGN AND SETTING: A multinomial model for low disease activity (submodel 1) and discontinuing due to AEs (submodel 2) was developed using data from the UK Rheumatoid Arthritis Medication Study, updated using landmarking analysis, internally validated using bootstrapping, and externally validated in the Norwegian Disease-Modifying Antirheumatic Drug register. Performance was assessed using calibration (calibration-slope and calibration-in-the-large), and discrimination (concordance-statistic and polytomous discriminatory index). RESULTS: The internally validated model showed good calibration in the development setting with a calibration-slope of 1.01 (0.87, 1.14) (submodel 1) and 0.83 (0.30, 1.34) (submodel 2), and moderate discrimination with a c-statistic of 0.72 (0.69, 0.74) and 0.53 (0.48, 0.59), respectively. Predictive performance decreased after external validation (calibration-slope 0.78 (0.64, 0.93) (submodel 1) and 0.86 (0.34, 1.38) (submodel 2)), which may be due to differences in disease-specific characteristics and outcome prevalence. CONCLUSION: We addressed previously identified methodological limitations of prediction models for outcomes of MTX therapy. The multinomial approach predicted outcomes of disease activity more accurately than AEs, which should be addressed in future work to aid implementation into clinical practice.

Socioeconomic deprivation is associated with reduced response and lower treatment persistence with TNF inhibitors in rheumatoid arthritis.

OBJECTIVE: To investigate the association between socioeconomic deprivation and outcomes following TNF inhibitor (TNFi) treatment. METHODS: Individuals commencing their first TNFi in the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) and Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) cohort were included. Socioeconomic deprivation was proxied using the Index of Multiple Deprivation and categorized as 20% most deprived, middle 40% or 40% least deprived. DAS28-derived outcomes at 6 months (BSRBR-RA) and 3 months (BRAGGSS) were compared using regression models with the least deprived as referent. Risks of all-cause and cause-specific drug discontinuation were compared using Cox models in the BSRBR-RA. Additional analyses adjusted for lifestyle factors (e.g. smoking, BMI) as potential mediators. RESULTS: 16 085 individuals in the BSRBR-RA were included (mean age 56 years, 76% female), of whom 18%, 41% and 41% were in the most, middle and least deprived groups, respectively. Of 3459 included in BRAGGSS (mean age 57, 77% female), proportions were 22%, 36% and 41%, respectively. The most deprived group had 0.3-unit higher 6-month DAS28 (95% CI 0.22, 0.37) and were less likely to achieve low disease activity (odds ratio [OR] 0.76; 95% CI 0.68, 0.84) in unadjusted models. Results were similar for 3-month DAS28 (ß = 0.23; 95% CI 0.11, 0.36) and low disease activity (OR 0.77; 95% CI 0.63, 0.94). The most deprived were more likely to discontinue treatment (hazard ratio 1.18; 95% CI 1.12, 1.25), driven by ineffectiveness rather than adverse events. Adjusted estimates were generally attenuated. CONCLUSION: Socioeconomic deprivation is associated with reduced response to TNFi. Improvements in determinants of health other than lifestyle factors are needed to address socioeconomic inequities.

The epidemiology of psoriatic arthritis in the UK: a health intelligence analysis of UK Primary Care Electronic Health Records 1991-2020.

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 26293 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 to 0.37. The standardized incidence of PsA per 100,000 person years increased from 8.97 in 1991 to 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.

Using Polygenic Risk Scores to Aid Diagnosis of Patients With Early Inflammatory Arthritis: Results From the Norfolk Arthritis Register.

OBJECTIVE: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G-PROB) has been developed to aid diagnosis has not yet been tested in a real-world setting. Our aim was to assess whether G-PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. METHODS: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G-probabilities (0%-100%) were created for each patient based on known disease-associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G-probabilities compared with clinician diagnosis was assessed. RESULTS: We tested G-PROB on 1,047 patients. Calibration of G-probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G-probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84-0.86). G-probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G-probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G-probability corresponded to clinician diagnosis. CONCLUSION: G-PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting.

Psychometric testing of the British-English Perceived Workplace Support Scale, Work Accommodations, Benefits, Policies and Practices Scale, and Work Transitions Index in four rheumatic and musculoskeletal conditions.

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.

Developing a framework for the implementation of recommendations for lifestyle factors for people with RMDs across Europe: assessment of current materials and implementation needs.

Lifestyle factors (such as diet, physical activity or smoking habits, among others) are known to influence the progression of rheumatic and musculoskeletal diseases (RMDs). Despite contemporary improvements in RMD care, the management of lifestyle factors is suboptimal. In the context of a recent European Alliance of Associations for Rheumatology (EULAR) task force, existing informative materials regarding lifestyle factors for people with RMDs were collected from national organisations across European countries. Current materials show important limitations in terms of coverage, literature support and access, which may make the implementation of successful interventions difficult. In the present viewpoint, a roadmap to cover these gaps at the European level with the recent EULAR recommendations on lifestyle factors is discussed from an implementation perspective. This analysis may pave the ground for future implementation endeavours at the European level related to non-pharmacological interventions that may also be applicable beyond rheumatology.

Psychometric testing of the British-English Long-Term Conditions Job Strain Scale, Long-Term Conditions Work Spillover Scale and Work-Health-Personal Life Perceptions Scale in four rheumatic and musculoskeletal conditions.

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.

Addressing education and employment outcomes in the provision of healthcare for young people with physical long-term conditions: A systematic review and mixed methods synthesis.

OBJECTIVE: To identify and synthesise the experiences and benefits of addressing vocational issues in the provision of healthcare for young people (YP) with long-term conditions (LTCs). METHODS: We searched 10 bibliographic databases. Restrictions were applied on publication date (1996-2020) and language (English). Two reviewers independently screened records against eligibility criteria. Articles reporting relevant qualitative and/or quantitative research were included. Quality appraisal was undertaken following study selection. Qualitative data were synthesised thematically, and quantitative data narratively. A cross-study synthesis integrated qualitative and quantitative findings. RESULTS: 43 articles were included. Thematic synthesis of qualitative studies (n = 23) resulted in seven recommendations for intervention (psychological support; information/signposting; skills training; career advice; healthcare-school/workplace collaboration; social support; flexible/responsive care). The narrative synthesis summarised results of 17 interventions (n = 20 quantitative studies). The cross-study synthesis mapped interventions against recommendations. Transitional care was the intervention type that most comprehensively met our proposed recommendations. CONCLUSIONS: Evidence from YP perspectives highlights that vocational development is an important area to address in healthcare provision. Robust intervention studies in this area are lacking. PRACTICE IMPLICATIONS: Our evidence-based recommendations for intervention can support health professionals to better address vocational issues/outcomes. With minimal adaptations, transitional care interventions would be particularly well suited to deliver this.

Psychometric testing of the British English Workplace Activity Limitations Scale in four rheumatic and musculoskeletal conditions.

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.

Which outcomes should always be measured in intervention studies for improving work participation for people with a health problem? An international multistakeholder Delphi study to develop a core outcome set for Work participation (COS for Work).

OBJECTIVE: Synthesising evidence of the effects of interventions to improve work participation among people with health problems is currently difficult due to heterogeneity in outcome measurements. A core outcome set for work participation is needed. STUDY DESIGN AND SETTING: Following the Core Outcome Measures in Effectiveness Trials methodology, we used a five-step approach to reach international multistakeholder consensus on a core outcome set for work participation. Five subgroups of stakeholders took part in two rounds of discussions and completed two Delphi voting rounds on 26 outcomes. A consensus of ≥80% determined core outcomes and 50%-80% consensus was required for candidate outcomes. RESULTS: Fifty-eight stakeholders took part in the Delphi rounds. Core outcomes were: 'any type of employment including self-employment', 'proportion of workers that return to work after being absent because of illness' and 'time to return to work'. Ten candidate outcomes were proposed, among others: 'sustainable employment', 'work productivity' and 'workers' perception of return to work'. CONCLUSION: As a minimum, all studies evaluating the impact of interventions on work participation should include one employment outcome and two return to work outcomes if workers are on sick leave prior to the intervention.

COVID-19-related anxiety trajectories in children, young people and adults with rheumatic diseases.

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.

Non-pharmacological interventions to promote work participation in people with rheumatic and musculoskeletal diseases: a systematic review and meta-analysis from the EULAR taskforce on healthy and sustainable work participation.

OBJECTIVE: To summarise the evidence on effectiveness of non-pharmacological (ie, non-drug, non-surgical) interventions on work participation (sick leave, work status and presenteeism) in people with rheumatic and musculoskeletal diseases (RMDs). METHODS: A systematic review of randomised controlled trials (RCTs) and longitudinal observational studies (LOS) was performed. Qualitative (RCTs/LOS) and quantitative (RCTs) evidence syntheses were conducted. Mixed-effects restricted maximum likelihood models were used to combine effect estimates, using standardised mean differences (SMDs) as the summary measure for each outcome domain separately, with a negative SMD favouring the intervention over comparator. Subgroup analyses were performed for type of RMD, risk status at baseline regarding adverse work outcomes and intervention characteristics. RESULTS: Of 10 153 records, 64 studies (37 RCTs and 27 LOS; corresponding to k=71 treatment comparisons) were included. Interventions were mostly conducted in clinical settings (44 of 71, 62%). Qualitative synthesis suggested clear beneficial effects of 7 of 64 (11%) interventions for sick leave, 1 of 18 (6%) for work status and 1 of 17 (6%) for presenteeism. Quantitative synthesis (37 RCTs; k=43 treatment comparisons) suggested statistically significant but only small clinical effects on each outcome (SMDsick leave (95% CI)=-0.23 (-0.33 to -0.13; k=42); SMDwork status=-0.38 (-0.63 to -0.12; k=9); SMDpresenteeism=-0.25 (-0.39 to -0.12; k=13)). CONCLUSION: In people with RMDs, empirical evidence shows that non-pharmacological interventions have small effects on work participation. Effectiveness depends on contextual factors such as disease, population risk status, intervention characteristics and outcome of interest, highlighting the importance of tailoring interventions.

Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.

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.

Genome-wide Association Study of Methotrexate-Induced Liver Injury in Rheumatoid Arthritis Patients.

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.

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

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.

Cognitive impairment in the immune-mediated inflammatory diseases compared with age-matched controls: Systematic review and meta-regression.

OBJECTIVES: To compare the magnitude of cognitive impairment against age-expected levels across the immune mediated inflammatory diseases (IMIDs: systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], psoriasis [PsO]). METHODS: A pre-defined search strategy was implemented in Medline, Embase and Psychinfo on 29/05/2021. Inclusion criteria were: (i) observational studies of an IMID, (ii) healthy control comparison, (iii) measuring cognitive ability (overall, memory, complex attention/executive function, language/verbal fluency), and (iv) sufficient data for meta-analysis. Standardised mean differences (SMD) in cognitive assessments between IMIDs and controls were pooled using random-effects meta-analysis. IMIDs were compared using meta-regression. RESULTS: In total, 65 IMID groups were included (SLE: 39, RA: 19, axSpA: 1, PsA: 2 PsO: 4), comprising 3141 people with IMIDs and 9333 controls. People with IMIDs had impairments in overall cognition (SMD: -0.57 [95% CI -0.70, -0.43]), complex attention/executive function (SMD -0.57 [95% CI -0.69, -0.44]), memory (SMD -0.55 [95% CI -0.68, -0.43]) and language/verbal fluency (SMD -0.51 [95% CI -0.68, -0.34]). People with RA and people with SLE had similar magnitudes of cognitive impairment in relation to age-expected levels. People with neuropsychiatric SLE had larger impairment in overall cognition compared with RA. CONCLUSIONS: People with IMIDs have moderate impairments across a range of cognitive domains. People with RA and SLE have similar magnitudes of impairment against their respective age-expected levels, calling for greater recognition of cognitive impairment in both conditions. To further understand cognition in the IMIDs, more large-scale, longitudinal studies are needed.

Association of vocational interventions and work-related factors with disease and work outcomes in people with RMDs: A systematic review.

OBJECTIVE: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours amongst people with rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on work-related factors and disease-specific outcomes for people with osteoarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis (SSc) and gout. METHODS: Two separate systematic literature reviews (SLRs) were conducted. The first identified SLRs, published between 01/2013 and 09/2018. The second identified original observational and intervention studies published before 05/2019. Manuscripts were included if they assessed the effects of vocational interventions on disease-specific outcomes (i.e. clinical outcomes, patient-reported outcomes, and work outcomes) or if they assessed the association between work-related factors and these outcomes. Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases were searched. RESULTS: Two SLRs were identified including individuals with SSc and inflammatory arthritis. Subsequently, 23 original manuscripts were identified, with most of them (43.5%) including people with RA and no manuscripts on gout. Most observational studies evaluated the association between work-related factors and work outcomes while limited information was available on the impact of work on clinical outcomes. A few studies suggested that physically demanding jobs have a small detrimental effect on radiographic progression in axSpA and PsA. Intervention studies showed beneficial effects of vocational interventions for disease-specific outcomes, but with small effect sizes. CONCLUSION: Many studies indicated that work participation is not likely to be detrimental and, in some cases, may be beneficial for RMD-specific outcomes and should therefore receive attention within healthcare consultations.

2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases.

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.