Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To 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.  Methods: A 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.  Results: Among 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.  Conclusion: Pharmacologic 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

Late Cretaceous (Maastrichtian) shallow water hydrocarbon seeps from Snow Hill and Seymour Islands, James Ross Basin, Antarctica

Fossil hydrocarbon seeps are present in latest Cretaceous (Maastrichtian) volcaniclastic shallow shelf sediments exposed on Snow Hill and Seymour Islands, James Ross Basin, Antarctica. The seeps occur in the Snow Hill Island Formation on Snow Hill Island and are manifest as large-sized, cement-rich carbonate bodies, containing abundant thyasirid bivalves and rarer ammonites and solemyid bivalves. These bodies have typical seep cement phases, with δ13C values between 20.4 and 10.7‰ and contain molecular fossils indicative of terrigenous organic material and the micro-organisms involved in the anaerobic oxidation of methane, including methanotrophic archaea and sulphate-reducing bacteria. On Seymour Island the seeps occur as micrite-cemented burrow systems in the López de Bertodano Formation and are associated with thyasirid, solemyid and lucinid bivalves, and background molluscan taxa. The cemented burrows also have typical seep cement phases, with δ13C values between 58.0 and 24.6‰. There is evidence from other data that hydrocarbon seepage was a common feature in the James Ross Basin throughout the Maastrichtian and into the Eocene. The Snow Hill and Seymour Island examples comprise the third known area of Maastrichtian hydrocarbon seepage. But compared to most other ancient and modern seep communities, the James Ross Basin seep fauna is of very low diversity, being dominated by infaunal bivalves, all of which probably had thiotrophic chemosymbionts, but which were unlikely to have been seep obligates. Absent from the James Ross Basin seep fauna are ‘typical’ obligate seep taxa from the Cretaceous and the Cenozoic. Reasons for this may have been temporal, palaeolatitudinal, palaeobathymetric, or palaeoecological