An observational cohort study evaluating adalimumab concentrations for predicting non-recapture of biochemical response after dose escalation in patients with Crohn’s disease experiencing secondary loss of response

Abstract Background There is limited evidence to support optimal concentrations for therapeutic drug monitoring in patients with Crohn’s disease (CD) who experience a loss of response (LOR) to tumour necrosis factor antagonists. This study aimed to determine the threshold trough adalimumab concentration beyond which patients with LOR are unable to recapture a response after dose escalation. Methods Enrolled patients had responded to adalimumab therapy after ≥16 weeks and subsequently experienced a secondary LOR, defined as a C-reactive protein (CRP) level ≥5 mg/L and/or a fecal calprotectin (FC) level ≥250 µg/g. Dosing was escalated from biweekly to weekly. Patients were then assessed for 12 weeks to determine their ability to recapture a response, defined as a CRP response (≥50% CRP decrease and/or CRP <5 mg/L) and/or FC response (≥50% FC decrease and/or FC <150 µg/g). The relationship between baseline trough concentration and non-recapture of biochemical response was evaluated using logistic regression. Results Of 97 enrolled patients, 49 (50.5%) did not recapture a response to adalimumab after dose escalation. Baseline trough concentration was not associated with non-recapture of biochemical response (odds ratio, 0.98; 95% CI: 0.91-1.06; P = .626). There was no threshold trough concentration identified that was predictive of non-recapture of biochemical response. No new adalimumab safety signals were identified. Conclusions No association was observed between trough adalimumab concentration and non-recapture of biochemical response after dose escalation for secondary LOR in CD. The threshold concentration above which dose escalation is ineffective remains unclear. ClinicalTrials.gov identifier: NCT02896985.