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P177 Lower vedolizumab trough levels before interval shortening are not predictive of success of the intervention

B. Ungar1,2, K. Malickova3, J. Hanžel4, M. Abu-Arisha5, S. Paul6, C. Rocha7,8, Z. Ben-Shatach1,2, O. Haj-Natour1,2, M. Yavzori1,2, E. Fudim1,2, O. Picard1,2, R. Eliakim1,2, U. Kopylov1,2, M. Lukas3, D. Drobne4,9, Y. Chowers5, X. Roblin6, F. Magro7, S. Ben-Horin1,2

1Sheba Medical Center Tel Hashomer, Gastroenterology Institute, Ramat gan, Israel, 2Tel-Aviv University, Sackler School of Medicine, Tel Aviv, Israel, 3ISCARE I.V.F. a.s ibd, IBD Clinical and Research Centre, Prague, Czech Republic, 4University Medical Centre Ljubljana, Department of Gastroenterology, Ljubljana, Slovenia, 5Rambam Health Care Campus, Bruce and Ruth Rappaport Faculty of Medicine, Haifa, Israel, 6University Hospital of Saint-Etienne, Department of Hepatogastroenterology, Saint-Etienne, France, 7University of Porto, Department of Biomedicine- Unit of Pharmacology and Therapeutics- Faculty of Medicine, Porto, Portugal, 8University of Lisbon, Instituto de Saúde Ambiental- Faculty of Medicine, Lisbon, Portugal, 9University of Ljubljana, Medical Faculty, Ljubljana, Slovenia

Background

Pharmacokinetics of vedolizumab have been associated with therapy outcome, although real-life data has been contradictory. Thus, we set to examine whether vedolizumab levels before therapy intensification may be associated with clinical, inflammatory and endoscopic outcomes further on.

Methods

In this retrospective cohort study, vedolizumab drug levels were determined in vedolizumab-treated patients with insufficient therapy response from six medical centers in Israel and Europe, before they underwent dose-intensification. The success of dose-increase gauged by clinical scores, inflammatory (C-reactive protein values, calprotectin) indices and endoscopic data was assessed vis-à-vis pre-escalation drug levels.

Results

Overall, 161 IBD patients (74, 46% Crohn’s disease) were included, of whom 32 patients underwent intensification at end-of-induction (week 10) and 129 during maintenance period (weeks 14–44, median week 30). In total, 34%, 60% and 30% of the 161 patients reached clinical, inflammatory and endoscopic remission by 6 months after intensification, respectively.

Among 129 patients intensified during maintenance period, pre-intensification trough levels were not lower among those reaching clinical and inflammatory remission after dose-escalation (median vedolizumab levels 34.4 vs. 24.4 μg/ml, 30.7 vs. 30.5 μg/ml, p = 0.09, 0.25 respectively). Patients who reached mucosal healing also had higher, rather than lower, vedolizumab levels before intensification (median vedolizumab levels 31.3 vs. 17 μg/ml, p = 0.04 for patients with and without mucosal healing, respectively).

Similarly, among 32 patients intensified at week 6 by an extra-dose at week 10, those with higher, while not lower, levels before escalation had higher rates of post-escalation clinical remission (median levels 101 vs. 61.5 μg/ml, p = 0.05). A similar trend was observed in terms of mucosal healing (88.5 vs. 43 μg/ml, p = 0.09) and inflammatory remission (median levels 100 vs. 55 μg/ml p = 0.15).

Conclusion

Lower vedolizumab trough levels before interval shortening were not predictive of success of the intervention. These results argue against a pharmacokinetic basis for insufficient response to vedolizumab and question the need for dose-escalation. A higher pre-escalation drug-level was associated with better later outcomes, possibly indicating a lower inflammatory burden, and may serve to predict patients with low likelihood to respond to therapy continuation.