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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 examine the rates of and risk factors for neutropenia together with the dynamics of neutrophil and other white cell subset counts in a cohort of patients treated with a tumor necrosis factor (TNF) inhibitor for inflammatory arthritis. Methods. We performed a retrospective cohort study examining the association between baseline demographics, clinical features, medications used, and development of neutropenia, and behavior of neutrophil and other white cell subset counts during TNF inhibitor therapy. Results. In 367 patients (298 [81.2%] with rheumatoid arthritis, 38 [10.4%] with ankylosing spondylitis, and 31 [8.4%] with psoriatic arthritis), 69 (18.8%) had at least one episode of neutropenia (<2.0 ؋ 10 9 /liter) during TNF inhibitor therapy, and of these, 6% developed serious infections secondary to neutropenia. There was no significant difference in disease, demographic, or drug variables between patients with and without neutropenia. However, patients with neutropenia had significantly lower baseline neutrophil counts (4.2 ؋ 10 9 /liter; 95% confidence interval [95% CI] 3.8, 4.6 versus 6.2 ؋ 10 9 /liter; 95% CI 6.0, 6.5), and a previous history of neutropenia while receiving disease-modifying antirheumatic drugs increased the risk while receiving TNF inhibitors (hazard ratio 2.97; 95% CI 1.69, 5.25). A significant drop in mean neutrophil count (1.12 ؋ 10 9 /liter; 95% CI 0.92, 1.32) was observed after 2 weeks of TNF inhibitor therapy. Other white cell subsets tended to significantly increase. Conclusion. TNF inhibitor therapy is associated with a significant reduction in peripheral blood neutrophil count, leading to 19% of patients becoming neutropenic. Risk of neutropenia is significantly higher in patients with a low baseline neutrophil count or previous history of neutropenia. We suggest that patients receiving TNF inhibitor therapy would benefit from regular complete blood cell count monitoring.

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