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.

Our clinical experience confirms that adalimumab is effective and safe in the treatment of RA. It also shows adalimumab is effective in patients with previous biological failures, particularly patients with secondary failure to infliximab.

Diffuse lung metastases have been reported in non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The purpose of our study was to compare the incidence of diffuse lung metastases in EGFR-mutant NSCLC and EGFR-wild type NSCLC and to assess other imaging features that may be associated with diffuse lung metastases in EGFR-mutant NSCLC. Two radiologists retrospectively reviewed pre-treatment imaging of metastatic NSCLC cases with known EGFR mutation status. We assessed the imaging features of the primary tumor and patterns of metastases. The cohort consisted of 217 patients (117 EGFR-mutant, 100 EGFR wild-type). Diffuse lung metastasis was significantly more common in EGFR-mutant NSCLC compared with wild-type (18% vs. 3%, p < 0.01). Among the EGFR-mutant group, diffuse lung metastases were inversely correlated with the presence of a nodule greater than 6 mm other than the primary lung lesion (OR: 0.13, 95% CI: 0.04–0.41, p < 0.01). EGFR mutations in NSCLC are associated with increased frequency of diffuse lung metastases. The presence of diffuse lung metastases in EGFR-mutant NSCLC is also associated with a decreased presence of other larger discrete lung metastases. EGFR mutations in NSCLC should be suspected in the setting of a dominant primary lung mass associated with diffuse lung metastases.