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.
Objective To develop a one week widening access summer school for 16 year old pupils from non-traditional backgrounds who are considering applying to medical school, and to identify its short term impact and key success factors. Design Action research with partnership schools in deprived inner city areas in five overlapping phases: schools liaison, recruitment of pupils and assessment of needs, programme design, programme delivery, and evaluation. The design phase incorporated findings from one to one interviews with every pupil, and workshops and focus groups for pupils, parents, teachers, medical student assistants, NHS staff, and other stakeholders. An in-depth process evaluation of the summer school was undertaken from the perspective of multiple stakeholders using questionnaires, interviews, focus groups, and observation. Participants 40 pupils aged 16 years from socioeconomically deprived and under-represented ethnic minority groups. Results The summer school was popular with pupils, parents, teachers, and staff. It substantially raised pupils' confidence and motivation to apply to medical school. Critical success factors were identified as an atmosphere of "respect"; a focus on hands-on work in small groups; the input of medical students as role models; and vision and leadership from senior staff. A particularly popular and effective aspect of the course was a grand round held on the last day, in which pupils gave group presentations of real cases. Conclusion An action research format allowed us to draw the different stakeholders into a collaborative endeavour characterised by enthusiasm, interpersonal support, and mutual respect. The input from pupils to the programme design ensured high engagement and low dropout rates. Hands-on activities in small groups and social drama of preparing and giving a grand round presentation were particularly important.
Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis.
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