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Absence of relationship between CDAI or CRP and infliximab exposure calls for objective Crohn's disease activity measures for the evaluation of treatment effects at treatment failure

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BACKGROUND: Circulating infliximab (IFX) concentrations correlate with clinical outcomes, forming the basis of the IFX concentration monitoring in patients with Crohn's disease. This study aims to investigate and refine the exposure-response relationship by linking the disease activity markers 'Crohn's disease activity index' (CDAI) and C-reactive protein (CRP) to IFX exposure. In addition, we aim to explore the correlations between different disease markers and exposure metrics.

METHODS: Data from 47 Crohn's disease patients of a randomized controlled trial were analyzed post hoc. All patients had secondary treatment failure at inclusion and had received intensified IFX of 5 mg/kg every 4 weeks for up to 20 weeks. Graphical analyses were performed to explore exposure-response relationships. Metrics of exposure included area under the concentration-time curve (AUC) and trough concentrations (Cmin). Disease activity was measured by CDAI and CRP values, their change from baseline/last visit and response/remission outcomes at week 12.

RESULTS: Although trends towards lower Cmin and lower AUC in non-responders were observed, neither CDAI nor CRP showed consistent trends of lower disease activity with higher infliximab exposure across the 30 evaluated relationships. As can be expected, Cmin and AUC were strongly correlated to each other. Contrarily, the disease activity markers were only weakly correlated to each other.

CONCLUSIONS: No significant relationship between disease activity, as evaluated by CDAI or CRP, and IFX exposure was identified. AUC did not add benefit compared to Cmin. These findings support the continued use of Cmin and call for stringent objective disease activity (bio-) markers (e.g., endoscopy) to form the basis of personalised IFX therapy for Crohn's disease patients with IFX treatment failure.

Original languageEnglish
JournalTherapeutic Drug Monitoring
Volume41(2)
Pages (from-to)235–242
Number of pages7
ISSN0163-4356
DOIs
Publication statusPublished - Apr 2019

ID: 56439605