Rheumatoid Arthritis: Hyrich K

Deighton C, Hyrich K. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18784124 No free full text.

This publication has no abstract.

Bowes JD, Potter C, Gibbons LJ, Hyrich K, Plant D, Morgan AW, Wilson AG, Isaacs JD, Worthington J, Barton A, Anonymous00030. · Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK. · Pharmacogenet Genomics. · Pubmed #19262425 No free full text.

Abstract: The introduction of anti-tumour necrosis factor (TNF) agents has greatly improved the treatment of rheumatoid arthritis; however, a significant proportion of patients fail to respond to therapy. We hypothesized that genes within the TNF receptor superfamily member 1B signalling pathway contribute towards the observed variation in patient response. This was tested by genotyping 73 single-nucleotide polymorphisms (SNPs) from six candidate genes (DUSP1, HRB, IKBKAP, MAP3K1, MAP3K14 and TANK) in a large UK cohort of rheumatoid arthritis patients (n=642). Two SNPs [rs96844 (MAP3K1) and rs4792847 (MAP3K14)] showed evidence of association (P<0.05) to treatment response and were subsequently examined in an independent cohort of patients (n=428). Replication of association to either SNP was not achieved, but combined analysis of the complete cohort (n=1070) provided nominal evidence of association to both SNPs. We conclude that analysis of the common variation in the selected candidate genes did not provide strong evidence to implicate their involvement in varying patient response to anti-TNF treatment.

Lunt M, Solomon D, Rothman K, Glynn R, Hyrich K, Symmons DP, Stürmer T, Anonymous00063, Anonymous00064. · arc Epidemiology Unit, University of Manchester, Stopford Building, Oxford Road, Manchester, United Kingdom. · Am J Epidemiol. · Pubmed #19153216 links to  free full text

Abstract: A number of covariate-balancing methods, based on the propensity score, are widely used to estimate treatment effects in observational studies. If the treatment effect varies with the propensity score, however, different methods can give very different answers. The authors illustrate this effect by using data from a United Kingdom-based registry of subjects treated with anti-tumor necrosis factor drugs for rheumatoid arthritis. Estimates of the effect of these drugs on mortality varied from a relative risk of 0.4 (95% confidence interval: 0.16, 0.91) to a relative risk of 1.3 (95% confidence interval: 0.8, 2.25), depending on the balancing method chosen. The authors show that these differences were due to a combination of an interaction between propensity score and treatment effect and to differences in weighting subjects with different propensity scores. Thus, the methods are being used to calculate average treatment effects in populations with very different distributions of effect-modifying variables, resulting in different overall estimates. This phenomenon highlights the importance of careful selection of the covariate-balancing method so that the overall estimate has a meaningful interpretation.

Deighton C, Hyrich K. · Derbyshire Royal Infirmary, Department of Rheumatology, Derby, UK. · Nat Clin Pract Rheumatol. · Pubmed #18665149 No free full text.

This publication has no abstract.

Adib N, Hyrich K, Thornton J, Lunt M, Davidson J, Gardner-Medwin J, Foster H, Baildam E, Wedderburn L, Thomson W. · Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK. · Rheumatology (Oxford). · Pubmed #18417527 links to  free full text

Abstract: OBJECTIVES: To study the association between disease severity at first presentation to paediatric rheumatology (PRh) and length of time since symptom onset in children recruited to the Childhood Arthritis Prospective Study. METHODS: Children <or=16 yrs with inflammatory arthritis persisting >or=2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses. RESULTS: Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation. CONCLUSIONS: Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.

Hyrich K, Symmons D, Watson K, Silman A, Anonymous00004, Anonymous00005. · ARC Unit, University of Manchester, Manchester, UK. · Ann Rheum Dis. · Pubmed #16339291 links to  free full text

Abstract: OBJECTIVE: To describe the occurrence of baseline comorbidity in subjects with active rheumatoid arthritis starting treatment with biological agents. Such data are necessary to interpret the reported occurrence of adverse events following treatment. METHODS: Baseline comorbidity was recorded in a large national cohort of patients with rheumatoid arthritis newly starting biological agents. The distribution of the number and types of comorbidities is presented. RESULTS: In all, 7818 patients treated with biological agents (infliximab 3332, etanercept 3302, adalimumab 1059, anakinra 132) were included in the analysis. Comorbidity was common, with 58% of patients having at least one comorbid condition and 25% having more than one. The most frequent comorbid conditions were hypertension, depression, peptic ulcer disease, and respiratory disease. CONCLUSIONS: In routine use, patients treated with biological agents have high levels of baseline comorbidity, which should influence the interpretation of reported adverse events.