Abstract
BACKGROUND: Therapeutic drug monitoring of adalimumab (ADA) is still controversial. OBJECTIVES: To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn's disease (CD). DESIGN: Retrospective cohort study. METHODS: Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation. RESULTS: In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, p = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, p = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, p = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, p < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all p-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (p = 0.02 and p = 0.001); and week 6 Q4 with BR at week 52 (p = 0.02), treatment persistence (p = 0.03), and lower dose escalation (p = 0.004). ADA trough levels at week 2 did not show similar associations. CONCLUSION: ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results.