Recent-onset Inflammatory Polyarthritis Research Articles

Association Between Socioeconomic Status (SES), Learned Helplessness (LH), and Prognosis in Patients with Inflammatory Polyarthritis

Objectives. To investigate the relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent .Methods. SES was measured using the Index of Multiple Deprivation 2007 for 553 patients. These patients were also measured by the Rheumatology Attitudes Index for their LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. Results. Compared to patients of the highest SES, those of the lowest SES had a worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a better outcome and patients with high LH had a worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a likelihood that LH mediated the association between SES and disease outcome (P 0.04)?. Conclusion. LH is associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications.

Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

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

O09. Factors Associated with Persistent, Intermittent or Never Achieving Remission in Patients with Recent-Onset Inflammatory Polyarthritis: Results he Norfolk Arthritis Register

O09. Factors Associated with Persistent, Intermittent or Never Achieving Remission in Patients with Recent-Onset Inflammatory Polyarthritis: Results he Norfolk Arthritis Register

OP0088 Changes in Baseline Severity of Inflammatory Polyarthritis Over Time

BackgroundPrevious research has suggested that the severity of rheumatoid arthritis (RA) has decreased over time.ObjectivesTo examine the pattern of disease severity in patients with inflammatory polyarthritis (IP) at time of...

OP0089 Disease Severity in Patients with Inflammatory Arthritis who Persistently, Intermittently, or Never Achieve Remission

BackgroundThe prognosis for patients with inflammatory polyarthritis (IP) varies and it is difficult to identify at onset which patients will ever achieve remission.ObjectivesTo examine the disease characteristics at i) baseline...

Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis

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

Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis.

ObjectiveIndependent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent.MethodsSES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated.ResultsCompared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04).ConclusionLH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications.

Influence of Inflammatory Polyarthritis on Quantitative Heel Ultrasound Measurements

BackgroundThere are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements.MethodsMen and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors.Results139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = −10.0; 95% confidence interval (CI) –17.4, -2.6) though BUA was similar (difference = −1.2; 95% CI −4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS.ConclusionsIn this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.

Influence of age and sex on functional outcome over time in a cohort of patients with recent‐onset inflammatory polyarthritis: Results from the Norfolk arthritis register

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). 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). 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. 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.

Multiple adverse pregnancy outcomes before symptom onset are associated with a worse disease outcome in women with recent-onset inflammatory polyarthritis

ObjectivePrevious evidence suggests that women with a history of adverse pregnancy outcomes (APOs) may be at greater risk of developing rheumatoid arthritis. Additionally, one study reported that female patients with...

The relationship between oral contraceptive use and functional outcome in women with recent‐onset inflammatory polyarthritis: Results from the Norfolk Arthritis Register

Use of oral contraceptives (OCs) may prevent the development of rheumatoid arthritis, but the influence of OC use on disease outcome is unresolved. The purpose of this study was to examine functional outcome and OC use in women with inflammatory polyarthritis (IP). The Norfolk Arthritis Register (NOAR) is an inception cohort of patients with recent-onset IP. We studied patient-reported history of OC use in 663 women who were born after 1945 and who had not used OCs during followup. OC use during followup was additionally investigated in 265 women who were <50 years old and had not undergone menopause or hysterectomy during followup. All patients were recruited to the NOAR between 1990 and 2004. Functional ability was assessed using the Health Assessment Questionnaire (HAQ), with adjustment for age at symptom onset. The median followup was 4.9 years. In the investigation analyzing OC use before symptom onset, patients who had used OCs before symptom onset had lower HAQ scores throughout followup than patients who had not taken OCs before symptom onset (difference in score at 5-year followup -0.35; 95% confidence interval [95% CI] -0.51, -0.19). Patients who were taking OCs at baseline had lower HAQ scores over time than women who were not taking OCs at baseline but had previously done so (mean difference -0.21; 95% CI -0.40, -0.02). In the investigation analyzing OC use during followup, OC use during followup was associated with lower HAQ scores over time than no OC use during followup (mean difference -0.06; 95% CI -0.16, 0.03); however, this was only significant for women with moderate or severe functional disability at the previous assessment (mean difference -0.23; 95% CI -0.40, -0.07). Further adjustment for potential confounders and exclusion of hormone replacement therapy users had little impact. OC use is generally associated with a beneficial functional outcome in IP, and use before and at symptom onset appeared to have the most consistent benefit.

Reduction of long‐term disability in inflammatory polyarthritis by early and persistent suppression of joint inflammation: Results from the Norfolk Arthritis Register

ObjectiveTo test the predictive ability of remission in terms of long-term disability in patients with recent-onset inflammatory polyarthritis (IP).MethodsConsecutive 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.ResultsA 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.ConclusionPatients 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.

A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register

Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.

The relationship between post-onset pregnancy and functional outcome in women with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register

ObjectiveTo examine the influence of post-symptom-onset pregnancy on disease outcome in women with inflammatory polyarthritis (IP).MethodsA total of 631 women, aged <48 years at symptom onset, were registered with the...

Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis: a primary care based inception cohort

BackgroundThe aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMDa) in a primary care based cohort of women with inflammatory polyarthritis.MethodsWomen aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10th anniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMDa (Hologic, QDR 4000). Linear regression was used to examine the association between BMDa with both (i) arthritis-related factors assessed at baseline and the 10th anniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age.Results108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMDa at both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10th anniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMDa at the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMDa at either site.ConclusionCumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.

Excess risk of hospital admission for cardiovascular disease within the first 7 years from onset of inflammatory polyarthritis

ObjectivesSubjects with rheumatoid factor positive inflammatory polyarthritis (IP) are known to have increased mortality from cardiovascular disease (CVD). A study was undertaken to examine the risk and baseline predictors of...

Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients

ObjectiveTo investigate whether recently identified rheumatoid arthritis (RA) susceptibility loci are also associated with disease severity, specifically all-cause and cardiovascular disease (CVD) mortality, in patients with inflammatory polyarthritis (IP).MethodsSubjects with recent-onset IP were recruited from the Norfolk Arthritis Register. Seventeen RA susceptibility single-nucleotide polymorphisms (SNPs) were tested using Sequenom MassArray iPLEX chemistry. Vital status was ascertained from central records. The association of SNP allele carriage with mortality risk was assessed using Cox proportional hazards models after adjusting by sex. The mortality risks of those SNP alleles found to be associated were then stratified by baseline anti–citrullinated peptide (anti-CCP) antibody and shared epitope (SE) status.ResultsAll SNPs were successfully genotyped in 2,324 IP subjects. The presence of 2 copies of the risk allele rs2812378 mapping to the CCL21 gene predicted all-cause mortality (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.04–1.87), whereas risk allele carriage also predicted increased CVD mortality (HR 1.33, 95% CI 1.01–1.75). The highest mortality risks were seen in anti-CCP antibody–positive subjects with 2 copies of the CCL21 risk alleles and 2 copies of the SE (all-cause HR 3.20, 95% CI 1.52–6.72; CVD HR 3.73, 95% CI 1.30–10.72).ConclusionIn this large study, we found that carriage of CCL21 risk alleles was associated with premature mortality in IP independently of anti-CCP antibody and SE status. Interestingly, CCL21 expression has been reported in atherosclerotic plaques supporting the thesis that the increased CVD mortality in IP patients may be mediated by shared inflammatory mechanisms.

The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register

Objectives. Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP).Methods. DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated.Results. Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score.Conclusion. Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets.

Early treatment with, and time receiving, first disease-modifying antirheumatic drug predicts long-term function in patients with inflammatory polyarthritis

ObjectivesTo investigate the influence of early disease-modifying antirheumatic drug (DMARD) treatment on long-term functional outcome in patients with recent-onset inflammatory polyarthritis (IP), and the impact of the duration of first...

The influence of age at symptom onset and length of followup on mortality in patients with recent‐onset inflammatory polyarthritis

ObjectiveTo investigate the influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration.MethodsFrom 1990 to 1994, patients with recent-onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all-cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality.ResultsOf 1,098 patients, 224 (20%) had died by the end of 2004. All-cause and CVD mortality were increased in rheumatoid factor (RF)–positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5-year followup 1.93 [95% confidence interval 1.08–3.19]; SMR 10-year followup 2.00 [95% confidence interval 1.37–2.80]). CVD mortality was highest in seropositive patients <55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24–11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score ≥1.5, and nodules were predictors of early and later mortality.ConclusionPatients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.