BACKGROUND: The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response. METHODS: Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study. Response was defined as cessation or significant improvement of fistula drainage. Patients with unavailable IFX level or ATI measurements and/or missing clinical follow-up at Week 14 were excluded. RESULTS: A total of 36 patients with perianal fistulae were included; 25/36 [69.4%] responded to treatment by Week 14. The median induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were higher compared with those of the non-responders group [20/5.6 µg/mL, P = 0.0001; 13.3/2.55 µg/mL P = 0.0001; 4.1/0.14 µg/mL, P = 0.01]. On multivariate analysis, IFX leve at Weeks 2 and 6 were significantly associated with fistula response at Weeks 14 and 30. IFX drug levels of 9.25 µg/mL at Week 2 and 7.25 µg/mL at Week 6 were the best predictors of fistula response. CONCLUSION: High IFX trough levels during induction are associated with favorable fistula response to anti-TNF treatment. If validated in a larger prospective study, our findings may help guide anti-TNF treatment in patients with perianal CD, and suggest serum level-guided treatment escalation in non-responders or prompt changing of biologic treatment in non-responders.
BACKGROUND: The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response. METHODS: Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study. Response was defined as cessation or significant improvement of fistula drainage. Patients with unavailable IFX level or ATI measurements and/or missing clinical follow-up at Week 14 were excluded. RESULTS: A total of 36 patients with perianal fistulae were included; 25/36 [69.4%] responded to treatment by Week 14. The median induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were higher compared with those of the non-responders group [20/5.6 µg/mL, P = 0.0001; 13.3/2.55 µg/mL P = 0.0001; 4.1/0.14 µg/mL, P = 0.01]. On multivariate analysis, IFX leve at Weeks 2 and 6 were significantly associated with fistula response at Weeks 14 and 30. IFX drug levels of 9.25 µg/mL at Week 2 and 7.25 µg/mL at Week 6 were the best predictors of fistula response. CONCLUSION: High IFX trough levels during induction are associated with favorable fistula response to anti-TNF treatment. If validated in a larger prospective study, our findings may help guide anti-TNF treatment in patients with perianal CD, and suggest serum level-guided treatment escalation in non-responders or prompt changing of biologic treatment in non-responders.
Authors: Konstantinos Papamichael; Adam S Cheifetz; Gil Y Melmed; Peter M Irving; Niels Vande Casteele; Patricia L Kozuch; Laura E Raffals; Leonard Baidoo; Brian Bressler; Shane M Devlin; Jennifer Jones; Gilaad G Kaplan; Miles P Sparrow; Fernando S Velayos; Thomas Ullman; Corey A Siegel Journal: Clin Gastroenterol Hepatol Date: 2019-03-27 Impact factor: 11.382