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.

No abstract

Objectives To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with rheumatoid arthritis (RA) starting methotrexate (MTX). Methods Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥ 18 years with physician diagnosed RA and symptom duration ≤ two years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at six- and twelve-month follow-up visits. The period prevalence rates of AEs are reported for 0–6 months, 6–12 months, and 0–12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression. Results A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematologic AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological), and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated Glomerular Filtration Rate (eGFR), and alcohol consumption were associated with less reporting of haematologic AEs. Conclusions AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AEs occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.

BackgroundThe University Hospitals of Leicester (UHL) NHS trust is one of the largest NHS hospital trusts in the United Kingdom. It serves a population of approximately one million, of which one-fifth identify as non-Caucasian, predominantly of South Asian origin. Ethnic differences in the characteristics of patients with Systemic Sclerosis (SSc) have been identified, with important clinical consequences, but there is little data on South Asians. The ethnic composition of our trust presents a unique opportunity to investigate this gap in our knowledge and improve disease outcomes in this cohort of patients.ObjectivesThe aim of this study was to investigate differences in the clinical manifestations of SSc patients between Caucasian and South Asians within UHL NHS Trust. We also investigated the screening of complications in these patients with echocardiography and annual pulmonary function tests (PFTs).MethodsSSc patients were identified from the connective tissue disease database of the UHL Rheumatology Department. Demographic data, clinical manifestations, immunology profile, PFTs and echocardiography results were collated from a combination of medical records at UHL including, radiology, pathology and Respiratory Physiology records. Treatment records were drawn from the DAWN database.ResultsA total of 70 SSc patients were identified, of which there were 10 (14%) South Asian, 58 (83%) Caucasian and 2 (3%) Black. We compared the following characteristics of the South Asian to the Caucasian population: Women 90.0 vs. 91.3% (p=0.89). Mean age 53.0 (95% CI 45.6-60.4, SD 12.0) vs. 62.2 (95% CI 58.9-65.6, SD 12.9) years (p<0.05). Mean age at diagnosis 45.2 (95% CI 36.2-54.2, SD 13.7) vs. 52.4 (95% CI 48.1-56.7, SD 16.0) years (p=0.21). Duration of disease 7.3 (95% CI 4.03-10.6, SD 5.1) vs. 8.9 (95% CI 6.5-11.5, SD 9.4) years (p=0.62). Limited disease 75.0 vs. 94.6% (p<0.05). Interstitial lung disease (ILD) 60.0 vs. 29.8% (p=0.64). Pulmonary Artery Hypertension 10.0 vs. 14.0% (p=0.74). Gastrointestinal complications 30.0 vs. 40.0% (p=0.50). Cardiac complications 0.0 vs. 10.3% (p=0.29). Raynaud's phenomenon 50.0 vs. 73.7% (p=0.13). Anti-Scl-70 antibody +ve 22.2 vs. 17.4% (p=0.73). Anti-centromere antibody +ve 50.0 vs. 31.0% (p=0.30). Current DMARD use 70.0 vs. 50.0% (p=0.24). Previous DMARD use 28.6 vs. 13.0% (p=0.29). Previous iloprost infusion 30.0 vs. 24.1% (p=0.70). Echocardiography 90.0 vs. 89.3% (p=0.94). Annual PFT 80.0 vs. 63.6% (p=0.24).ConclusionsA minority (14%) of SSc patients in Leicestershire are South Asian, similar to the ethnic composition of Leicestershire.The mean age of onset is significantly lower in the South Asian group compared to the Caucasian group.The South Asian group had significantly more diffuse SSc disease compared to the Caucasian group.The prevalence of ILD was twice as high in the South Asian group compared to the Caucasian group.The usage of annual PFTs and echocardiography did not differ significantly between the South Asian and Caucasian groups.Disclosure of InterestNone declared

Objectives To understand the relationships between deprivation and obesity with self-reported disability and disease activity in people with RA; and whether BMI mediates the relationship between area-level deprivation and these outcomes. Methods Data came from the Rheumatoid Arthritis Medication Study (RAMS), a one-year multicentre prospective observational cohort of people with RA recruited from rheumatology centres across England commencing methotrexate for the first time. 1529 and 1626 people were included who had a baseline and at least one follow-up measurement at 6 or 12 months of Health Assessment Questionnaire—Disability Index (HAQ-DI) and Disease Activity Score-28 (DAS28), respectively. Linear mixed models estimated the associations of deprivation and obesity with repeated measures HAQ-DI and DAS28. Causal mediation analyses estimated the mediating effect of BMI on the relationship between deprivation and RA outcomes. Results Higher deprivation and obesity were associated with higher disability (adjusted regression coefficients highest vs lowest deprivation fifths 0.32 (95% CI 0.19, 0.45); obesity vs no obesity 0.13 (95% CI 0.06, 0.20)) and higher disease activity (adjusted regression coefficients highest vs lowest deprivation fifths 0.34 (95% CI 0.11, 0.58); obesity vs no obesity 0.17 (95% CI 0.04, 0.31)). BMI mediated part of the association between higher deprivation and self-reported disability (14.24%) and disease activity scores (17.26%). Conclusions People with RA living in deprived areas have a higher burden of disease, which is partly mediated through obesity. Weight-loss strategies in RA could be better targeted towards those living in deprived areas.