Arthritis Research UK and Medical Research Council.

ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

ObjectiveTo examine mortality rates in UK patients with early rheumatoid arthritis (RA) from 1990–2011 and compare with population trends.MethodsThe Norfolk Arthritis Register (NOAR) recruited adults with ≥2 swollen joints for ≥4 weeks: cohort 1 (1990–1994), cohort 2 (1995–1999), and cohort 3 (2000–2004). At baseline, serum rheumatoid factor and anti–citrullinated protein antibody were measured and the 2010 American College of Rheumatology/European League Against Rheumatism RA classification criteria were applied. Patients were followed for 7 years, until emigration or death. The UK Office for National Statistics notified the NOAR of the date and cause of deaths, and provided mortality rates for the Norfolk population. All-cause and cardiovascular-specific standardized mortality ratios (SMRs) were calculated. Poisson regression was used to compare mortality rate ratios (MRRs) between cohorts and then, with cubic splines, to model rates by calendar year. Analyses were performed in patients 1) with early inflammatory arthritis, 2) classified as having RA, and 3) autoantibody positive.ResultsA total of 2,517 patients were included, with 1,639 women (65%) and median age 55 years, and 1,419 (56%) fulfilled the 2010 RA criteria. All-cause and cardiovascular-specific SMRs were significantly elevated in the antibody-positive groups. There was no change in mortality rates over time after accounting for changes in the population rates. In RA patients, all-cause MRRs, compared to cohort 1, were 1.13 (95% confidence interval [95% CI] 0.84–1.52) and 1.00 (95% CI 0.70–1.43) in cohorts 2 and 3, respectively.ConclusionMortality rates were increased in patients with RA and SMRs were particularly elevated in those who were autoantibody positive. Compared to the general population, mortality rates have not improved over the past 20 years.

ObjectivesThe development of new classification criteria for rheumatoid arthritis (RA) calls for a re-estimation of RA incidence rates. The objectives of this study were to estimate the age and sex-specific incidence rates (IR) of RA in Norfolk, England using the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism criteria, and to compare those with IRs estimated using the 1987 ACR criteria.SettingThe Norfolk Arthritis Register (NOAR), a large primary care inception cohort of patients with inflammatory oligo- and polyarthritis (IP) aged ≥ 16.MethodsAll patients notified to NOAR from 1990-5 with symptom onset in 1990 were included. The former Norwich Health Authority population was the denominator. Age and sex specific IRs using 1987 and 2010 classification criteria were calculated at baseline visit, annually for the first 3 years and at 5 years.Results260 patients were notified to NOAR with symptom onset in 1990 and without an alternative diagnosis. IRs applying the 2010 criteria at baseline were 54/100 000 for women and 25/100 000 for men. Age and sex-specific IRs using the 2010 classification criteria at baseline were similar to cumulative IRs applying the 1987 criteria up to 5 years. However, some patients only ever satisfied one set of criteria and a proportion of IA patients (20%) did not satisfy either criteria set over 5 years.ConclusionsThe 2010 criteria classify similar numbers of patients as having RA at baseline, as the 1987 criteria would have taken up to 5 years to identify.

ObjectivesTo investigate the association of lifestyle factors with risk of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).MethodsThe European Prospective Investigation of Cancer, Norfolk, UK (EPIC-Norfolk) gathered lifestyle data from participants aged 40–79 years from 1993 to 1997. Individuals who subsequently developed IP were identified by linkage with the Norfolk Arthritis Register. A Cox proportional hazard model was developed, and a score assigned to each risk factor to calculate the odds of developing IP.Results25 455 EPIC participants were followed for a median (IQR) of 14.2 (12.9, 15.3) years; 184 developed incident IP (138 cumulatively fulfilled criteria for RA; 107 were seropositive). Pack-years of smoking were associated with increased risk of IP and RA in men (HR 1.21 (95% CI 1.08 to 1.37) per 10-pack-years) and seropositive IP (HR 1.24 (95% CI 1.10 to 1.41)) for all. Diabetes mellitus was associated with increased risk of IP (HR 2.54 (95% CI 1.26 to 5.09)), while alcohol (HR 0.86 (95% CI 0.74 to 0.99) per unit/day) and higher social class (HR 0.36 (95% CI 0.15 to 0.89) for professionals vs manual workers) were associated with reduced risk. Body mass index was associated with seronegative IP (HR 2.75 (95% CI 1.39 to 5.46) for obese vs normal-weight participants). In women, parity (HR 2.81 (95% CI 1.37 to 5.76) for ≥2 vs no children) was associated with increased risk, and breast feeding (HR 0.66 (95% CI 0.46 to 0.94) for every 52 weeks of breast feeding) was inversely associated with risk. Risk factors from the model were used to generate a ‘risk score’. A total of 1159 (8.4%) women had scores reflecting a >3-fold increased risk of IP over those with a score of 0.ConclusionsSeveral easily ascertained clinical and lifestyle factors can be used to stratify populations for risk of IP.

Objectives-To determine the frequency of overuse injury in indoor climbers, the common sites of such injury, and the factors that influence the probability that a climber will have sustained an overuse injury while climbing indoors. Method-A semisupervised questionnaire was used to survey overuse injury in 295 spectators and competitors at the EntrePrises World Climbing Championships held in Birmingham 3-5 December 1999. Statistical analysis included simple cross tabulations, calculation of odds ratios, and multiple logistic regression to explore the eVect of several factors simultaneously. Results-Some 44% of respondents had sustained an overuse injury, 19% at more than one site. The most common site of injury was the fingers. Univariate analysis showed that the probability of having sustained a climbing injury is higher in men (p = 0.009), those who have climbed for more than 10 years (p = 0.006), those who climb harder routes (p<0.0005), and those who boulder or lead more than they top rope (p<0.0005). The relation between lead grade and climbing injury is linear. Multivariate analysis removed the eVect of sex as an independent predictor. Conclusions-Many climbers sustain overuse injury. The most at risk are those with the most ability and dedication to climbing. Climbers should be aware of the risk factors that influence injury and be able to spot the signs and symptoms of injury once they occur. (Br J Sports Med 2001;35:181-185)

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The Screening for Osteoporosis in Older Women for the Prevention of Fracture (SCOOP) study was a community-based screening intervention in women aged 70 to 85 years in the United Kingdom. In the screening arm, licensed osteoporosis treatments were recommended in women identified to be at high risk of hip fracture using the FRAX risk assessment tool (including bone mineral density measurement). In the control arm, standard care was provided. Screening led to a 28% reduction in hip fractures over 5 years. In this planned post hoc analysis, we wished to examine for interactions between screening effectiveness on fracture outcome (any, osteoporotic, and hip fractures) on the one hand and baseline FRAX 10-year probability of hip fracture on the other. All analyses were conducted on an intention-to-treat basis, based on the group to which women were randomized, irrespective of whether screening was completed. Of 12,483 eligible participants, 6233 women were randomized to screening, with treatment recommended in 898 (14.4%). No evidence of an effect or interaction was observed for the outcomes of any fracture or osteoporotic fracture. In the screening arm, 54 fewer hip fractures were observed than in the control arm (164 versus 218, 2.6% versus 3.5%), and commensurate with treatment being targeted to those at highest hip fracture risk, the effect on hip fracture increased with baseline FRAX hip fracture probability (p = 0.021 for interaction); for example, at the 10th percentile of baseline FRAX hip probability (2.6%), there was no evidence that hip fractures were reduced (hazard ratio [HR] = 0.93; 95% confidence interval [CI] 0.71 to 1.23), but at the 90th percentile (16.6%), there was a 33% reduction (HR = 0.67; 95% CI 0.53 to 0.84). Prior fracture and parental history of hip fracture positively influenced screening effectiveness on hip fracture risk. We conclude that women at high risk of hip fracture based on FRAX probability are responsive to appropriate osteoporosis management. © 2018 American Society for Bone and Mineral Research.