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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. [ABSTRACT FROM AUTHOR]

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

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

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

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. [ABSTRACT FROM AUTHOR]

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

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]

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. [ABSTRACT FROM AUTHOR]

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

Objective: Approximately 30–40% of rheumatoid arthritis (RA) patients who are initially started on low‐dose methotrexate (MTX) will not benefit from the treatment. To date, no reliable biomarkers of MTX inefficacy in RA have been identified. The aim of this study was to analyze whole blood samples from RA patients at 2 time points (pretreatment and 4 weeks following initiation of MTX), to identify gene expression biomarkers of the MTX response. Methods: RA patients who were about to commence treatment with MTX were selected from the Rheumatoid Arthritis Medication Study. Using European League Against Rheumatism (EULAR) response criteria, 42 patients were categorized as good responders and 43 as nonresponders at 6 months following the initation of MTX treatment. Data on whole blood transcript expression were generated, and supervised machine learning methods were used to predict a EULAR nonresponse. Models in which transcript levels were included were compared to models in which clinical covariates alone (e.g., baseline disease activity, sex) were included. Gene network and ontology analysis was also performed. Results: Based on the ratio of transcript values (i.e., the difference in log2‐transformed expression values between 4 weeks of treatment and pretreatment), a highly predictive classifier of MTX nonresponse was developed using L2‐regularized logistic regression (mean ± SEM area under the receiver operating characteristic [ROC] curve [AUC] 0.78 ± 0.11). This classifier was superior to models that included clinical covariates (ROC AUC 0.63 ± 0.06). Pathway analysis of gene networks revealed significant overrepresentation of type I interferon signaling pathway genes in nonresponders at pretreatment (P = 2.8 × 10−25) and at 4 weeks after treatment initiation (P = 4.9 × 10−28). Conclusion: Testing for changes in gene expression between pretreatment and 4 weeks post–treatment initiation may provide an early classifier of the MTX treatment response in RA patients who are unlikely to benefit from MTX over 6 months. Such patients should, therefore, have their treatment escalated more rapidly, which would thus potentially impact treatment pathways. These findings emphasize the importance of a role for early treatment biomarker monitoring in RA patients started on MTX. [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]

Objective: Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries.Methods: Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages >18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received ≥1 synthetic disease-modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch.Results: Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts.Conclusion: Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well-defined cohort definitions. [ABSTRACT FROM AUTHOR]

Purpose Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries. Methods We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data. Results Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data. Conclusions Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements. [ABSTRACT FROM AUTHOR]

Objective It has been found that women with rheumatoid arthritis (RA) have a poorer prognosis than men. However, the impact of age at symptom onset is unclear. We investigated the relationship between these factors and functional disability in patients with recent-onset inflammatory polyarthritis (IP). Methods A total of 3,666 patients (66% women) were registered with the Norfolk Arthritis Register between 1990 and 2008. Functional disability was assessed using the Health Assessment Questionnaire (HAQ), adjusted for age at HAQ completion. Linear random-effects models were used to examine HAQ score over time, by sex and age at symptom onset (early = age <55 years, late = age 55-74 years, very late = age ≥75 years). Results Women had higher HAQ scores over time than men (mean difference 0.29; 95% confidence interval [95% CI] 0.25, 0.34). Men with late-onset IP had lower baseline HAQ scores than men with early onset (mean difference −0.14; 95% CI −0.29, −0.001). Women had comparable baseline HAQ scores at all ages of onset. Both sexes showed the greatest rate of disability progression in patients with very late onset. Those with early onset had a steady level of disability over time. Adjustment for treatment received, comorbidities, and RA subgroup analysis produced results that were largely similar to the initial analysis. Conclusion Female patients have higher HAQ scores than male patients; patients with early symptom onset show the smallest sex difference. Older age at symptom onset is associated with an increasingly steep trajectory of disability progression. The impact of sex on outcome is evident at baseline, whereas the impact of age at symptom onset becomes apparent during long-term followup. [ABSTRACT FROM AUTHOR]

Objective To test the predictive ability of remission in terms of long-term disability in patients with recent-onset inflammatory polyarthritis (IP). Methods Consecutive patients with early IP, recruited between 1990 and 1994 (first cohort) and 2000 and 2004 (second cohort), were included in this study. Remission was defined as the absence of clinically detectable joint inflammation on a 51-joint count. In additional analyses, less stringent definitions of remission were used based on the 40- and 28-joint counts. Remission was assessed at 1, 2, and 3 years after inclusion. A 5-year Health Assessment Questionnaire score ≥1 (moderate disability) was chosen as the primary outcome measure. Results A total of 841 and 498 patients from the first and second cohorts, respectively, completed 5 years of followup. In the first cohort, patients with at least 1 episode of remission had lower odds of 5-year disability (odds ratio [OR] 0.26, 95% confidence interval [95% CI] 0.17-0.41). The number of times in remission correlated with the odds of disability, with a mean decrease in the probability of disability of ∼64% for each additional time point in remission (OR 0.38, 95% CI 0.28-0.52). The time until first remission was not associated with functional disability. Remission according to less stringent criteria showed a weaker protection against future disability. Similar results were found in the second cohort. Conclusion Patients with IP achieving a state of sustained remission early are less likely to show long-term deterioration of function compared with patients who do not achieve remission. The most persistent remission under the most stringent definition of remission has the lowest probability of long-term disability. [ABSTRACT FROM AUTHOR]