N J Wiles

Estimating the incidence of rheumatoid arthritis: Trying to hit a moving target

OBJECTIVE To examine the effect of delay between symptom onset and notification to an arthritis register and the effect of application of the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria in a cumulative manner on estimates of the incidence of rheumatoid arthritis (RA). METHODS General practitioners and/or hospital consultants in the Norwich Health Authority, Norfolk, UK, notified the Norfolk Arthritis Register (NOAR) of all patients who had onset of inflammatory polyarthritis (swelling of > or =2 joints) during 1990. The patients were assessed within 2 weeks of notification and annually thereafter. The ACR 1987 criteria for RA were applied at each assessment. Age- and sex-specific incidence rates were calculated. RESULTS If up to 12 months elapsed from symptom onset to notification to NOAR and the ACR criteria were applied at the baseline assessment, RA incidence estimates, age-adjusted to the population of England and Wales, were 30.8/100,000 for women and 12.7/100,000 for men. If up to 5 years elapsed from symptom onset to notification, these estimates rose by 45% for women and 36% for men. If up to 5 years elapsed between symptom onset and notification and the criteria were applied cumulatively, the estimates rose by 75% and 93% for women and men, respectively, compared with the 1-year data, reaching 54.0/100,000 for women and 24.5 per 100,000 for men. CONCLUSION Accurate estimation of the incidence of RA requires long-term followup of patients who present with undifferentiated inflammatory polyarthritis. The highest age-adjusted estimates from this study are probably the best that are available.

Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis: results from a large, population-based study.

OBJECTIVE To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.

The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis.

OBJECTIVE Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA). In this study, we examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP). METHODS We studied 486 patients with IP who were referred to the Norfolk Arthritis Register, of whom 323 (67%) satisfied the American College of Rheumatology 1987 criteria for RA. Smoking status was assessed at baseline. Disease outcome was assessed at 3 years, using measures of joint inflammation, functional disability, and radiologic damage. The influence of smoking on disease outcome was explored using logistic regression techniques, with patients who had never smoked as the referent group. Results are expressed as odds ratios (ORs), with their 95% confidence intervals (95% CIs). RESULTS Current smokers were significantly more likely to be RF positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%). After 3 years, rheumatoid nodules were significantly more common in smokers (13%) compared with ex-smokers/never smokers (4%), a relationship which persisted after adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting for age and sex, current smokers had significantly fewer swollen joints (OR 0.61, 95% CI 0.37-0.98). However, smoking status had no influence on the development of erosions or functional disability. CONCLUSION Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage.

The influence of HLA–DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis

OBJECTIVE There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis. The exact role of these alleles in short-term outcome is determined in this large, prospective, population-based study. METHODS We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods. Disease outcome was assessed at 2 years in terms of persistent joint inflammation, functional disability, and radiologic erosions. Results are expressed as risk ratios (RR) with 95% confidence intervals (95% CI). RESULTS There was no influence of HLA-DRB1 alleles, in any combination, on the likelihood of disease persistence, and only a modest effect on functional disability (Health Assessment Questionnaire score > or = 1). The most obvious effect was on the development of erosions (RR 1.9, 95% CI 1.4-2.6 for those who carried at least 1 DRB1 shared epitope [SE] allele), with slightly greater effects for those who were homozygous for SE-bearing alleles (RR 2.5, 95% CI 1.8-3.6). This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor. Among patients with erosions, HLA-DRB1 had no influence on the severity of radiologic damage (defined as the number of eroded joints, or total Larsen score). CONCLUSION These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease.

Benchmarking: the five year outcome of rheumatoid arthritis assessed using a pain score, the Health Assessment Questionnaire, and the Short Form-36 (SF-36) in a community and a clinic based sample

BACKGROUND Treatment, and therefore outcome, of rheumatoid arthritis (RA) will improve in the next few years. However, improvement in outcome can only be judged against the probability of certain outcomes with current conventional treatment. AIM To document the five year outcome of RA in the late 1990s. SETTING Norfolk Arthritis Register (NOAR). DESIGN Longitudinal observational cohort study. METHODS 318 patients with recent onset inflammatory polyarthritis recruited by NOAR in 1990–91 completed five years of follow up. Four groups were assessed: the whole cohort, all those referred to hospital, those who satisfied criteria for RA at baseline, and those referred to hospital who satisfied criteria for RA at baseline. Outcome was assessed with a visual analogue scale for pain, the Health Assessment Questionnaire (HAQ), and the Short Form-36 (SF-36). RESULTS Of the RA hospital attenders, 50% had a visual analogue scale pain score of 5 cm or less and an HAQ score of 1.125 or less. SF-36 scores were reduced in all domains. Results are presented as cumulative percentages. CONCLUSIONS These results can be used for comparison and to set targets for improvement.

Associations between demographic and disease-related variables and disability over the first five years of inflammatory polyarthritis: A longitudinal analysis using generalized estimating equations

OBJECTIVES To investigate whether the relationship between demographic and disease-related variables and disability is constant during the first five years of inflammatory polyarthritis (IP) and to identify the contribution from involvement of specific joint areas to overall disability. METHODS 684 patients referred to the Norfolk Arthritis Register were followed for five years using the Health Assessment Questionnaire (HAQ). The relationship between disability and demographic and clinical variables was analyzed using a multi-level modelling approach. RESULTS Female gender, older age at symptom onset (> or = 64 years), joint involvement at six specific sites, joint tenderness and the number of deformed joints were all independently associated with disability (HAQ > or = 1.00). Similar results were obtained using a more stringent cut-off (HAQ > or = 1.50) or when analysis was restricted to the 325 patients who satisfied the 1987 ARA list criteria for rheumatoid arthritis. CONCLUSION Disability, as measured by the HAQ, was associated with a large number of independent factors over the first five years of disease.