BACKGROUND: Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response. OBJECTIVE: The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. PATIENTS AND METHODS: This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n=536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. RESULTS: During VDZ induction, at week 6, inflammatory bowel disease patients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P=0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval=0.567-0.878, P=0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P=0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P=0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. CONCLUSION: We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction.
BACKGROUND:Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response. OBJECTIVE: The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. PATIENTS AND METHODS: This study focused on a single cohort of 103 inflammatory bowel diseasepatients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n=536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. RESULTS: During VDZ induction, at week 6, inflammatory bowel diseasepatients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P=0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval=0.567-0.878, P=0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P=0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P=0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. CONCLUSION: We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction.
Authors: Luisa Guidi; Daniela Pugliese; Tommaso Panici Tonucci; Lorenzo Bertani; Francesco Costa; Giuseppe Privitera; Barbara Tolusso; Clara Di Mario; Eleonora Albano; Gherardo Tapete; Elisa Gremese; Alfredo Papa; Antonio Gasbarrini; Gian Ludovico Rapaccini; Alessandro Armuzzi Journal: United European Gastroenterol J Date: 2019-09-03 Impact factor: 4.623
Authors: Patrizio Scarozza; Irene Marafini; Federica Laudisi; Edoardo Troncone; Heike Schmitt; Marco Vincenzo Lenti; Stefania Costa; Irene Rocchetti; Elena De Cristofaro; Silvia Salvatori; Ludovica Frezzati; Antonio Di Sabatino; Raja Atreya; Markus F Neurath; Emma Calabrese; Giovanni Monteleone Journal: J Clin Med Date: 2020-02-01 Impact factor: 4.241
Authors: Lorenzo Bertani; Gian Paolo Caviglia; Luca Antonioli; Rinaldo Pellicano; Sharmila Fagoonee; Marco Astegiano; Giorgio Maria Saracco; Elisabetta Bugianesi; Corrado Blandizzi; Francesco Costa; Davide Giuseppe Ribaldone Journal: J Clin Med Date: 2020-05-02 Impact factor: 4.241