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.
(RPE) and percentage of 1RM while performing resisted knee extension, and (2) to examine test-retest reliability of RPE in a general population of adults. Methods: Following determination of 1RM, participants performed 1-3 repetitions of knee extension at ten equal increments of the determined 1RM (10%-100% of 1RM) in random order. Participants stated perceived exertion rating for each level of resistance. This protocol was repeated 5-10 days later to determine test-retest reliability. Spearman rho correlations were calculated to assess correlation between 1RM and RPE, as well as test-retest reliability. Sensitivity, specificity, Youden's index, and likelihood ratios were calculated to determine optimal RPE cutoff values for use in dosage of resistive exercise. Results: 14 female and 12 male participants completed the study (mean age 45.3, SD 18.4, range 21.0-81.4). 27% of participants selfreported knee OA, and 19% reported a history of unilateral lower extremity surgery. A good-to-excellent correlation was found between 1RM and RPE (Spearman rho, 0.787, p < .001; see Figure 1 for Bland-Altman plot). In addition to the overall relationship between the two dosage methods, moderate correlations were determined to exist between percentage of 1RM and RPE at each resistance interval (see Table 1). Test-retest reliability was excellent (Spearman rho, 0.830, p < .001, see Figure 2 for Bland-Altman plot). Area under the curve was high at each resistance interval (0.83-0.92), indicating that RPE strongly predicted percentage of 1RM at each interval from 20% through 90% of 1RM. Table 2 represents these data and suggested RPE cutoff values to approximate each percentage of 1RM for use in dosage of strengthening exercises.
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