Norfolk Arthritis Register Research Articles

Harnessing genetics in the outpatient clinic using polygenic risk scores to aid diagnosis of patients with early inflammatory arthritis: results from the Norfolk Arthritis Register

Harnessing genetics in the outpatient clinic using polygenic risk scores to aid diagnosis of patients with early inflammatory arthritis: results from the Norfolk Arthritis Register

P059 Informal care for those with multiple longer term conditions - a hidden burden?

Abstract Background/Aims Multiple long-term conditions (MLTC) refers to the co-existence of two or more chronic conditions. Rheumatic diseases (RMDs) are important long-term conditions which are common in individuals with MLTC. The effect of rheumatic disease on disability is well known and often requires support with activities of daily living, i.e. social care. However, while the presence of MLTC is known to be associated with social care need, the role of RMDs in driving social care need is unknown. This lack of data capture of social care resource use undermines healthcare strategy. We carried out two surveys in different parts of the country to ascertain the social care burden amongst those with RMDs. Methods An online cross-sectional survey to identify and characterise formal and informal social care use was sent to two different groups of patients with rheumatic and musculoskeletal disease. The first comprised participants within Norfolk Arthritis Register, who were emailed an invitation to complete the survey between March-July 2023. As part of Assembling the Data Jigsaw programme, the second group comprised patients attending the Salford Royal Hospital Rheumatology Department with text message invitations sent between October 2022-September 2023 via the DrDoctor app. All participants answered identical questions on formal and informal care provision and demographic characteristics. Logistic regression was used to identify factors associated with needing support. Results A total of 184 participants within the NOAR cohort completed the survey, comprising 128 (70%) women with a median age of 64 years. A total of 439 participants completed the survey in the Salford Royal Hospital cohort, comprising 326 (74%) women with a median age of 58 years. Rheumatoid arthritis was reported by 93 (73%) of the NOAR recruits and 136 (31%) of the Salford Royal Hospital cohort, with osteoarthritis the next most common with 37 (20%) and 112 (34%) of each cohort reporting this condition. Using self-reported data, 47% and 64% of the respective cohorts met the criteria for MLTC. For both cohorts, 30% reported needing four hours or fewer assistance per week, and 19% reported requiring >10 hours a week. Although infrequent or occasional help was usually provided informally by spouses, partners, family members or friends, 42 (23%) of the NOAR cohort and 70 (16%) of the Salford Royal Hospital cohort arranged formal care provision themselves without involving the council. Multivariable logistic regression of both cohorts found that those who were younger were more likely to have reported needing assistance with ADLs in the last month. MLTC was also associated with requiring help. Conclusion The majority of individuals engage informal support or arrange care without help from local authorities. These data are important for describing social care resource use and for determining healthcare strategy. Disclosure M. Yates: None. M. Soomro: None. A. Onajole: None. A. MacGregor: None. W. Dixon: None. J. McBeth: None. J.H. Humphreys: None.

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

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. 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. 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. 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.

P042 Using a Genetic PROBability tool (G-PROB) to aid diagnosis of patients with inflammatory arthritis: results from the Norfolk Arthritis Register

Abstract Background/Aims Recent translational advances in genetics report the ability to accurately predict the diagnosis of patients presenting with synovitis, providing potential to accelerate treatment and improve patient outcomes. One tool is G-PROB, which uses genetic information to calculate conditional probabilities, known as G-probabilities ranging from 0 to 100%, for defined diseases. In the original study, G-PROB was configured to discriminate between patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and “other rheumatological diseases” using reported bias-adjusted odds ratios from 250 known single nucleotide polymorphisms and human leukocyte antigen variants of uncorrelated risk variants. The original study tested G-PROB on 243 patients with synovitis. Our aim was to assess whether G-PROB could aid diagnosis using data from the Norfolk Arthritis Register (NOAR), a large observational cohort of patients with early inflammatory arthritis. Methods Genotypes, and clinician diagnosis were obtained from NOAR. The same prevalence settings and risk variants as the original study were used. Six G-probabilities each corresponding to one disease were created for each patient and performance was assessed using linear regression without intercept, negative and positive predictive values (NPV, PPV), and receiver-operator-curve (ROC) analysis. Results From NOAR, 2031 genotyped patients were identified and underwent case note review to determine the clinician diagnosis. Clinician diagnoses included RA (n = 767), PsA (n = 106), SpA (n = 15), SLE (n = 14), gout (n = 5), and “other” (n = 65). For n = 1059, case notes were not available resulting in exclusion. The mean G-probability was 41% for those which corresponded to clinician-defined disease, which was significantly higher compared to 12% for those that did not (95%CI -0.30 to -0.28). As reported in the original study, G-probabilities were concordant with real disease status (β regression coefficient of 1.03 vs 0.99, where 1.00 is ideal). We found 42% of all G-probabilities were &amp;lt;5%, corresponding to a NPV of 99%, where it was possible to deprioritise &amp;gt;1 disease for 100% of patients, &amp;gt;2 diseases for 96% of patients, and &amp;gt;3 diseases for 69% of patients. We found 17.8% of patients had a single G-probability &amp;gt;50% corresponding to a PPV of 41%. This compared to 45% of patients, and PPV of 64% reported in the original study. Accuracy of G-probabilities to discriminate clinician-defined disease was similar in our cohort (AUC of 0.86 95% CI 0.84-0.87) compared to the original study (AUC 0.84 95% CI 0.81-0.86). In 57% of patients in our cohort, the disease with the highest G-probability corresponded to the clinician-defined disease compared to 53% in the original study. Conclusion We were able to replicate several findings of the original study in a large independent cohort including calibration, high NPV, but PPV was lower, suggesting that G-PROB is most valuable as a tool to rule out diagnoses. Disclosure R.M. Hum: None. S.D. Sharma: None. M. Stadler: None. N. Nair: None. S. Viatte: None. C. Yap: None. J.H. Humphreys: None. A. MacGregor: None. M. Yates: None. M. Soomro: None. S.M. Verstappen: None. P. Ho: None. A. Barton: None. J. Bowes: None.

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). 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]). 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. 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.

HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory polyarthritis independent of CRP and anti-CCP status

BackgroundHaplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA) are associated with radiological outcome, anti-TNF response and all cause-mortality in RA. RA is associated with cardiovascular (CV) morbidity and mortality, but the increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim of this study was to investigate whether amino acids at positions 11, 71 and 74 of HLA-DRB1 are associated with cardiovascular (CV) mortality in inflammatory polyarthritis (IP).MethodsThe Norfolk Arthritis Register (NOAR) is an incidence register of IP: recruitment 1990–2007, final follow-up 2011. Two thousand five hundred fourteen patients had available genetic and mortality data. Amino acids at positions 11, 71 and 74 of HLA-DRB1 were determined. Univariate Cox proportional hazard models were applied to assess the association of genetic markers and both all-cause mortality and cardiovascular mortality.ResultsAmong 2514 participants, 643 (25.6%) died during the study, and 343 (53.3%) of these deaths were attributed to CV causes. One thousand six hundred fifty (65.6%) participants were female, 709 (32.3%) were anti-CCP-positive and the median age of participants was 54.HLA-DRB1 haplotypes associated with susceptibility to rheumatoid arthritis (RA) consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p=0.023). Mediation analysis revealed associations were independent of anti-CCP status.ConclusionsHLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors. Associations were independent of anti-CCP status, which suggests in the future, genetic factors will add to the prediction of risk of cardiovascular mortality beyond serological markers.

OA28 Exploring the potential of polygenic risk scores for predicting coronary artery disease in patients with rheumatoid arthritis

Abstract Background/Aims Patients with rheumatoid arthritis (RA) have a higher prevalence of coronary artery disease (CAD) than the general population which contributes to early mortality. Current screening tools for CAD, which are developed in the general population, are less effective for estimating CAD risk in patients with RA. This reduced performance is mainly due to the differing contribution from traditional risk factors and the contribution from disease-specific factors. Our understanding of the genetic basis of CAD has improved over recent years and shows promise for improving risk prediction in the form of polygenic risk scores (PRS). We hypothesise that PRS can help us improve CAD risk prediction in patients with RA by providing more accurate models of risk. Methods Patients were recruited from the Norfolk Arthritis Register (NOAR), a detailed community-based longitudinal observational study focused on the cause and outcome of inflammatory polyarthritis, between 1990 and 2017. Analysis was restricted to patients who satisfied the 2010 ACR criteria cumulatively over five years and had detailed clinical history at baseline and follow-up. We developed a prediction model based on traditional risk factors and explored the inclusion of a PRS (49K SNPs) in a subset of patients with available genetic data. Cox proportional hazards models were used to derive risk equations for evaluation of 10-year risk of CAD. We applied multiple imputations with chained equations using the Random Forest algorithm to replace missing values. Measures of calibration and discrimination were determined in the validation cohort of 423 individuals. Results A total of 2123 patients were included in the analysis with 136 incident cases of self-reported CAD. The model using only traditional risk factors achieved an AUC of 0.72 (95% CI 0.71, 0.73), with a calibration slope of 1.03, and explained approximately 50% (95% CI 47, 52%) of the variance of the outcome. We found that being male reduces the risk by a factor of 0.82 (95% CI 0.68, 1.00). The hazard ratio for age was found to be 1.00 (95% CI 0.99, 1.01) indicating risk remains the same across all age groups. Inclusion of a CAD PRS increased the performance with an AUC of 0.76 (95% CI 0.75, 0.77), explained variance of 53% (95% CI 49, 56%) but with a slightly worse calibration slope of 0.91. Conclusion An integrated risk score, that combines traditional risk factors with a PRS, improves CAD prediction in patients with RA. Further research is required to better understand the role of heritable components contributing to CAD risk in RA patients. By refining the underlying PRS, we hope to further improve CAD risk prediction in RA patients, through this integrated approach. Disclosure M. Soomro: None. M. Stadler: None. S. Viatte: None. A. MacGregor: None. S. Verstappen: None. A. Barton: None. J. Bowes: None.

P213 HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory arthritis

Abstract Background/Aims Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA), are associated with radiological outcome, anti-TNF response and all cause-mortality. RA is associated with cardiovascular (CV) morbidity and mortality, but increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim was to investigate whether haplotypes associated with RA disease susceptibility and disease severity are associated with CV mortality. Methods The Norfolk Arthritis register (NOAR) is a primary care-based inception cohort of patients with inflammatory polyarthritis (IP). NOAR patients with at least 2 years of follow-up and available mortality and genetic data were included. Mortality data was provided by the Office for National Statistics. Univariate Cox proportional hazard models were applied using STATA/IC 14.0. Models for CV mortality were adjusted for CV risk factors selected using stepwise regression: namely obesity, gender and hypertension. Hazard models were applied to the entire cohort of patients with inflammatory polyarthritis (IP). When calculating differences between highest and lowest risk genetic factors, bivariate analysis was used. Results HLA-DRB1 amino acids, haplotypes or haplotype groups associated with RA susceptibility are also associated with CV mortality as shown in the table. HLA-DRB1 polymorphisms encoding amino-acid haplotypes associated with an increased or decreased susceptibility to RA consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p = 0.023). The relative difference in CV mortality between carriers of the high susceptibility VKA haplotype and carriers of the SEA haplotype was significant (HR 1.67, 95% CI 1.13, 2.48, p = 0.01). Associations were independent of anti-CCP status. Conclusion HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors and anti-CCP status, which suggests that, in the future, genetic factors will add to prediction of risk of cardiovascular mortality beyond serological markers. Disclosure S.D. Sharma: None. D. Plant: None. J. Bowes: Grants/research support; British Heart Foundation. A. Macgregor: None. A. Barton: Grants/research support; BMS. Other; Speaker Fees from Roche Chugai. S. Viatte: None.

Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.

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

Reduced cognitive ability in people with rheumatoid arthritis compared with age-matched healthy controls.

ObjectiveThe aim was to compare the cognitive ability of people with RA with healthy controls (HCs).MethodsPeople with RA were recruited from the Norfolk Arthritis Register (NOAR), a population-based cohort study of people with inflammatory arthritis. Data on aged-matched HCs (people with no cognitive impairment) came from the comparison arm of The Dementia Research and Care Clinic Study (TRACC). People with RA and HCs performed a range of cognitive ability tasks to assess attention, memory, verbal fluency, language, visuospatial skills, emotional recognition, executive function and theory of mind. A score of <88 on the Addenbrooke’s Cognitive Examination III was considered cognitive impairment. Scores were compared using linear regression adjusting for age, sex, smoking status, education, BMI, anxiety and depression.ResultsThirty-eight people with RA [mean (S.D.) age: 69.1 (8.0) years; 25 (65.8%) women] were matched with 28 HCs [mean (S.D.) age: 68.2 (6.4) years; 15 (53.6%) women]. Twenty-three (60.5%) people with RA were considered to have mild cognitive impairment [mean (S.D.) Addenbrooke’s Cognitive Examination III: RA = 85.2 (7.4), HC = 96.0 (2.5)]. People with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with HCs, after adjustment for confounders.ConclusionPeople with RA had cognitive impairments in a range of domains. People with RA might benefit from cognitive impairment screening to allow for early administration of appropriate interventions.

THU0130 PATTERNS OF COGNITIVE DECLINE IN RHEUMATOID ARTHRITIS: RESULTS OF CASE CONTROL STUDY NESTED IN A POPULATION-BASED COHORT

Background:The risk of cognitive decline and dementia is of particular interest for patients exposed to prolonged inflammation. In rheumatoid arthritis (RA), the inflammatory mechanisms that are central to the disease’s pathology share many features with those seen in Alzheimer’s disease (AD). However, published reports on the strength and direction of the putative associations with cognitive decline and dementia in RA are conflicting and the potential impact of immunomodulation has not been fully established. This study reports on a case control analysis comparing the results of a cognitive test conducted in RA cases from a longitudinal population register with healthy controls. The relationship between test outcomes, disease characteristics, and treatment is examined.Objectives:To characterise differences in cognitive function as assessed by a validated test battery between a group of patients with RA and a matched sample of healthy controls.To investigate disease and treatment related factors that might have an impact on the cognitive function of patients with RA.Methods:A total of 38 people with RA were selected at random from subjects who had enrolled on the Norfolk Arthritis Register as part of the ICORA (Investigation of Cognition in RA) Study. The register is a large longitudinal inception cohort of patients recruited from both primary and secondary care. The study subjects were over 55 years old with a diagnosis of RA defined by the ACR criteria. Cognitive function was assessed using the Addenbrooke’s Cognitive Examination III (ACE-III) battery. The ACE-III is a validated screening test for dementia that evaluates five cognitive domains (attention, memory, verbal fluency, language and visuospatial skills). A cut off value of 82 is indicative of cognitive impairment. The ACE-III scores in the cases were compared with scores from 29 healthy population-based controls matched for age and sex.Results:The mean age of the patient and control groups was 69 years. The RA patients had a mean disease duration of 9.8 years and had been taking DMARDs for 7.1 years. Among the patient group with RA, 14 (37%) scored below 82 compared with none in the group of healthy controls. The mean ACE-III scores of both groups are shown in the table below:Controls N=29RA N=38ACE-III Total95.2 (3.7)85.2 (7.4)•Attention17.7 (0.5)16.5 (1.9)•Memory24.6 (1.9)19.8 (4.0)•Fluency12 (1.4)9.9 (2.6)•Language25.5 (0.8)24.6 (1.7)•Visuospatial15.8 (0.5)14.4 (1.5)After adjusting for age, sex, BMI and smoking status, significant differences were seen in the ACE-III total (adjusted mean difference(SE)=8.67(1.77); p&lt;0.001), memory (adjusted mean difference(SE)=4.16(1.03); p&lt;0.001), fluency (adjusted mean difference(SE)=2.29(0.67); p=0.001) and visuospatial (adjusted mean difference(SE)=1.36(0.38); p&lt;0.001). There was no difference in attention (p=0.19) or language (p=0.10).Among the patients with RA there was no clear association between disease duration and ACE-III Total scores; however, there was a trend for increasing cognitive scores in those who had been taking DMARDs for longer (&lt;5 years: mean ACE-III Total=84.1; 5-10 years: 85.0: 11-14 years: 85.4; &gt;14 years: 89.6).Conclusion:This study provides evidence to suggest that patients with established RA are at increased risk of cognitive decline when compared with healthy controls. The pattern of cognitive deficit, predominantly involving visuospatial and memory function, is consistent with an Alzheimer’s disease profile. Our data suggest a potential role for DMARDs in reducing the rate of cognitive decline in patients with RA.Disclosure of Interests:Tasuku Toyoda: None declared, Jacqueline Chipping: None declared, Jack Dainty: None declared, Stephen Jeffs: None declared, Michael Hornberger: None declared, Eneida Mioshi: None declared, Suzanne Verstappen Grant/research support from: BMS, Consultant of: Celltrion, Speakers bureau: Pfizer, Max Yates: None declared, Alex MacGregor: None declared

215 Predictors of resilience in severe rheumatoid arthritis: an analysis of data from the Norfolk Arthritis Register

215 Predictors of resilience in severe rheumatoid arthritis: an analysis of data from the Norfolk Arthritis Register

O14 Pro-inflammatory diets are associated with increased C-reactive protein and subsequent rheumatoid arthritis in the European Investigation of Cancer: Norfolk Arthritis Register cohort

O14 Pro-inflammatory diets are associated with increased C-reactive protein and subsequent rheumatoid arthritis in the European Investigation of Cancer: Norfolk Arthritis Register cohort

160 Vascular calcification on hand and feet radiographs as a potential cardiovascular risk stratification tool: results from the Norfolk Arthritis Register

160 Vascular calcification on hand and feet radiographs as a potential cardiovascular risk stratification tool: results from the Norfolk Arthritis Register

O10 The association of high sensitivity troponin levels with subsequent cardiovascular mortality in an inflammatory arthritis cohort: results from the Norfolk arthritis register

O10 The association of high sensitivity troponin levels with subsequent cardiovascular mortality in an inflammatory arthritis cohort: results from the Norfolk arthritis register

Risk factors for oral methotrexate failure in patients with inflammatory polyarthritis: results from a UK prospective cohort study

BackgroundOral 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.MethodsSubjects 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.ResultsA 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.ConclusionsRF-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.

Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register

ObjectiveTo compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart.MethodsPatients with IP were recruited to the Norfolk Arthritis...

Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme

ObjectivePatients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study...

Twenty-Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results From the Norfolk Arthritis Register.

ObjectiveTo 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.MethodsPatients 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.ResultsThis 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]).ConclusionThe results of this study indicate the importance of early treatment with regard to the long‐term outcomes in patients with RA.

Predictors of and outcomes following orthopaedic joint surgery in patients with early rheumatoid arthritis followed for 20 years.

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