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.
In the present study a group of four indigenous and less popular rice genotypes (Meghi, Panibhasha, Jabra and Sholey) reported by growers as submergence tolerant lines from flood prone areas of south Bengal were explored through study of nodal anatomy, physio-biochemical screening under submergence and genotyping with submergence tolerance linked rice microsatellite loci (RM loci). To identify the different allelic forms of different Sub1 compnents (Sub1A, Sub1B and Sub1C) among the studied lines, the genomic DNA of individual genotypes was amplified with three ethylene response factor like genes from Sub1 loci, located on rice chromosome 9. From the different physio-biochemical experiments performed in this investigation, it has been shown that Meghi and Jabra are the two probable potent genotypes which share common properties of both submergence tolerant and deep water nature whereas rest two genotypes (Sholey and Panibhasha) behave like typical deep water rice. The submergence tolerance property of Meghi was also confirmed from submergence tolerance linked SSR based genotyping by sharing with FR13A for some common alleles as reflected in fingerprint derived dendrogram. The rest of the genotypes shared a number of alleles and were included in a separate cluster. The common behaviour of Meghi and FR13A under submergence was also confirmed from genetic study of Sub1 loci through sharing of some common alleles for three Sub1 components (Sub1A, Sub1B and Sub1C loci). One SSR loci (RM 285) was identified as a potent molecular marker for submergence tolerance breeding programme involving these two selected rice lines (Meghi and Jabra) as donor plant through marker assisted
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