Rheumatoid Arthritis: Wiles N

Wiles N, Dunn G, Barrett E, Silman A, Symmons D. · ARC Epidemiology Unit, University of Manchester Medical School, Manchester, UK. · J Clin Epidemiol. · Pubmed #11027930 No free full text.

Abstract: 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.

Harrison B, Thomson W, Symmons D, Ollier B, Wiles N, Payton T, Barrett E, Silman A. · University of Manchester, UK. · Arthritis Rheum. · Pubmed #10524690 links to  free full text

Abstract: 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.

Wiles N, Symmons DP, Harrison B, Barrett E, Barrett JH, Scott DG, Silman AJ. · University of Manchester Medical School, UK. · Arthritis Rheum. · Pubmed #10403260 links to  free full text

Abstract: 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.

Wiles N, Barrett J, Barrett E, Silman A, Symmons D. · ARC Epidemiology Research Unit, University of Manchester, UK. · J Rheumatol. · Pubmed #10229399 No free full text.

Abstract: OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.

Thomson W, Harrison B, Ollier B, Wiles N, Payton T, Barrett J, Symmons D, Silman A. · Epidemiology Research Unit, Manchester University Medical School, UK. · Arthritis Rheum. · Pubmed #10211891 links to  free full text

Abstract: 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.