Association of morbid obesity with disability in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: Obesity has been associated with disease outcomes in inflammatory arthritis. This study aimed to investigate cross-sectionally the relationship between body mass index (BMI) and functional disability in a large inception cohort of patients with early inflammatory polyarthritis (IP). METHODS: Patients age ≥16 years with ≥2 swollen joints for ≥4 weeks were recruited into the Norfolk Arthritis Register. At the initial assessment, clinical and demographic data were obtained, joints were examined, and height and weight were measured. Blood samples were taken to measure inflammatory markers and autoantibodies, and patients completed the Health Assessment Questionnaire (HAQ) to assess functional disability. Univariate and multivariate ordinal regression were used to examine the cross-sectional association between BMI and the HAQ. Multiple imputation using chained equations allowed inclusion of patients with missing variables. RESULTS: A total of 1,246 patients were studied (median age 57 years). Of those patients, 782 patients (63%) were female and 303 (25%) were obese (BMI ≥30 kg/m(2) ). Morbid obesity (BMI ≥35 kg/m(2) ) was significantly associated with worse functional disability in the univariate and multivariate analysis with missing data imputed, adjusting for age, sex, symptom duration, smoking status, disease activity, autoantibodies, comorbidities, and treatment (multivariate odds ratio 1.87, 95% confidence interval 1.14-3.07). CONCLUSION: Morbid obesity in patients with early IP is associated with worse HAQ scores. This should be taken into account in patient management and when interpreting the HAQ in clinical practice.

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.

Parity, time since last live birth and long-term functional outcome: a study of women participating in the Norfolk Arthritis Register.

OBJECTIVE: To investigate the relationship between pre-symptom onset live births and functional outcome in women with inflammatory polyarthritis (IP). METHODS: 1872 women with no subsequent pregnancies were registered with the Norfolk Arthritis Register between 1990 and 2004 and followed-up for a median of 5 years. Functional disability over time was assessed by Health Assessment Questionnaire (HAQ). The number and calendar year of past live births were recorded. Differences in HAQ score over time by parity and time since last live birth (latency), adjusted for age and symptom duration, were examined using linear random effects models. The results were then adjusted for a number of potential confounders. RESULTS: 1553 women (83%) had ≥1 live births before symptom onset. The median latency was 26 years (IQR 16-35). Parous women had significantly lower HAQ scores over time than nulliparous women (-0.19, 95% CI -0.32 to -0.06). Increasing latency was associated with increasing HAQ score; the mean HAQ score of women with a latency of approximately 32 years was the same as for nulliparous women. This was independent of autoantibody status, socioeconomic status, smoking history and comorbidity. CONCLUSION: Parous women who develop IP have better functional outcome over time than nulliparous women who develop IP. The beneficial effect of parity diminishes with time.

Incidence of lymphoma in a large primary care derived cohort of cases of inflammatory polyarthritis.

OBJECTIVE: To determine the risk of lymphoma in a primary care derived cohort of new onset cases of inflammatory polyarthritis and assess the contribution of disease severity and standard immunosuppressive treatment. DESIGN: Prospective cohort study. METHODS: 2105 subjects with new onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) and followed annually for (median) 8.4 years. Occurrence of lymphoma was determined by annual morbidity review and linkage to the central hospital database serving the NOAR area. Cases of lymphoma were verified by record review. Standardised incidence ratios (SIRs) for lymphoma were calculated compared with the local, age, sex, and calendar year expected rates. Stratified analyses were undertaken for various markers of disease severity and treatment history. RESULTS: There were 11 cases of lymphoma during 15,548 person years of follow up, the majority of which were of large B cell type. Compared with the local population the SIR was 2.4 (95% confidence interval, 1.2 to 4.2). The risks in cases classified as rheumatoid arthritis, ever rheumatoid factor positive, or ever treated with DMARDs were all higher, the highest risk group being those treated with methotrexate: SIR = 4.9 (1.8 to 10.6). CONCLUSIONS: There was a doubling in risk of lymphoma in new onset cases of inflammatory polyarthritis. Patients with the most severe disease were twice as likely as other patients to develop lymphoma. These results need to be taken into account when considering reported increased risks of lymphoma compared to background population risk in users of new biological agents.

Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study.

OBJECTIVE: To investigate whether, there is an association between consumption of fruit and vegetables and dietary antioxidants and the risk of developing inflammatory polyarthritis (IP). METHODS: In a prospective, population based, nested case-control study of residents of Norfolk, UK, men and women aged 45-74 years were recruited, between 1993 and 1997 through general practice age-sex registers to the Norfolk arm of the European Prospective Investigation of Cancer (EPIC-Norfolk). Dietary intake was assessed at baseline using 7 day diet diaries. Seventy three participants who went on to develop IP between 1993 and 2001 and were registered by the Norfolk Arthritis Register (NOAR) were identified. Incident cases of IP, assessed by general practitioners, fulfilled the criteria of two or more swollen joints, persisting for a minimum of 4 weeks. Each case of IP was matched for age and sex with two controls free of IP. RESULTS: Lower intakes of fruit and vegetables, and vitamin C were associated with an increased risk of developing IP. Those in the lowest category of vitamin C intake, compared with the highest, increased their risk of developing IP more than threefold, adjusted odds ratio (OR) with 95% confidence intervals (CI) 3.3 (95% CI 1.4 to 7.9). Weak inverse associations between vitamin E and beta-carotene intake and IP risk were found. CONCLUSION: Patients with IP (cases) consumed less fruit and vitamin C than matched controls, which appeared to increase their risk of developing IP. The mechanism for this effect is uncertain. Thus similar studies are necessary to confirm these results.

Traditional cardiovascular risk factors measured prior to the onset of inflammatory polyarthritis.

BACKGROUND: Cardiovascular mortality is increased in patients with seropositive inflammatory polyarthritis (IP). We tested the hypothesis that the increased risk of cardiovascular disease (CVD) can be explained by elevated traditional CVD risk factor levels in persons prior to development of IP. METHODS: In a population-based, prospective nested case-control study, 25 600 people aged 45-75 yr participated in a health survey, including standard CVD risk factor assessment, between the years 1993 and 1997. There were 91 incident IP cases (one-third were seropositive at presentation) identified during follow-up to the end of July 2001. Baseline CVD risk factors in the IP cases were compared with those in two age/gender-matched controls. RESULTS: Current smokers had an odds ratio of 2.0 (95% CI 1.0-4.0) for IP. Other risk factors, including total and LDL cholesterol, systolic and diastolic blood pressure and obesity, did not differ significantly between cases and controls. Importantly, in combination, using a standard coronary disease risk score, these factors only had a modest association with future IP, and no association when analysis was restricted to the smaller number of cases who were seropositive. CONCLUSION: Of the traditional cardiovascular risk factors, only smoking increases CVD risk prior to the onset of IP. Therefore the increased CVD observed in these patients is likely to be a consequence of factors operating after the onset of the arthritis.