P483 Infliximab but not adalimumab drug levels predict faecal calprotectin response in Inflammatory Bowel Disease patients on dose-intensified anti-TNF therapy
Noack, S.(1);Little, R.(1);Vaz, K.(1);Ward, M.(1);Sparrow, M.(1);
(1)Alfred Health and Monash University, Department of Gastroenterology, Melbourne, Australia
Background
Secondary loss of response (SLOR) to infliximab (IFX) and adalimumab (ADA) is common and dose intensification is effective in a proportion of patients. Drug level targets associated with response as measured by faecal calprotectin (FCP) after anti-TNF intensification have not been well established.
Methods
Retrospective observational study of consecutive adult patients with Crohn’s disease (CD) or ulcerative colitis (UC) with SLOR commenced on dose-intensified IFX (5mg/kg 6 weekly) or ADA (40mg weekly) between May 2013-August 2020. Patients were managed via a protocolised virtual clinic. Trough anti-TNF drug levels and FCP were measured at baseline, and at 6 and 12 months post dose intensification. FCP response was defined as ≤150μg/g. Inter-group and longitudinal comparisons used Mann-Whitney U and Wilcoxon signed-rank tests, respectively. ROC curves evaluated anti-TNF drug levels predictive of FCP response.
Results
Of 78 patients (56% male, median age 40 years), 60 had CD (58% on IFX) and 18 had UC (100% on IFX). There were no significant differences in patient or disease demographics between FCP responders and non-responders at 6 or 12 months. At 6 months, median IFX level and increment in level from baseline were higher in FCP responders than non-responders in both CD and UC (Table 1). At 6 months, achieving an IFX level ≥5.7μg/mL in CD (AUC 0.82, sensitivity 88%, specificity 65%, p=0.012; Figure 1A) and an IFX level ≥5.2μg/mL in UC (AUC 0.89, sensitivity 100%, specificity 73%, p=0.015; Figure 1B) best predicted FCP response. ADA levels at 6 months and both IFX and ADA levels at 12 months were not predictive of FCP response in any cohort.
| FCP≤150μg/g | FCP>150μg/g | p-value | n | |
|---|---|---|---|---|
| CD IFX levels 6months | 7.7 | 4.5 | 0.011 | 25 |
| CD Δ in IFX levels 0-6months | 5.5 | 3.3 | 0.038 | 23 |
| UC IFX levels 6months | 11 | 2.7 | 0.013 | 16 |
| UC Δ in IFX levels 0-6months | 8.7 | 1.5 | 0.028 | 15 |
| CD ADA levels 6months | 10 | 10 | 0.999 | 15 |
| CD Δ in ADA levels 0-6months | 5.9 | 6.6 | 0.535 | 14 |
| CD IFX levels 12months | 8.4 | 6.2 | 0.114 | 17 |
| CD Δ in IFX levels 0-12months | 5.7 | 4.4 | 0.536 | 16 |
| UC IFX levels 12months | 9.4 | 13 | 0.117 | 10 |
| UC Δ in IFX levels 0-12months | 6.6 | 11 | 0.067 | 10 |
| CD ADA levels 12months | 11 | 12 | 0.814 | 14 |
| CD Δ in ADA levels 0-12months | 7.6 | 7.9 | 0.937 | 13 |
Table 1. Median infliximab (IFX) and adalimumab (ADA) levels (μg/mL) and increment according to faecal calprotectin (FCP) response in Crohn’s disease (CD) and ulcerative colitis (UC).
Figure 1: ROC curves of infliximab (IFX) levels and faecal calprotectin (FCP) response in CD (A) and UC (B) patients at 6 months.
Conclusion
After dose-intensified IFX, CD and UC patients achieving FCP response had greater absolute and increment in drug levels than those with elevated FCP. IFX levels ≥5.7μg/mL and ≥5.2μg/mL at 6 months are predictive of FCP response in CD and UC, respectively. ADA levels were not predictive of FCP response.