Long-Term Outcome of Patients with Ulcerative Colitis and Primary Non-response to Infliximab.

Abstract

BACKGROUND AND AIMS:

We studied the long-term outcome of patients with ulcerative colitis [UC] and primary non response [PNR] to infliximab and searched for predictors of colectomy in these patients.

METHODS:

This retrospective, multi-centre study included UC patients from three European referral centres, with PNR to infliximab defined as a lack of clinical improvement after the induction therapy, leading to drug discontinuation. Relapse, for patients who continued on biologicals after PNR to infliximab, was defined as drug discontinuation for PNR, loss of response, or serious adverse event. Serum infliximab concentrations at Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA] developed in house.

RESULTS:

The study population consisted of 99 anti-tumour necrosis factor [TNF]-naïve patients with UC and PNR to infliximab. At the end of follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these patients underwent colectomy. Multiple Cox regression analysis identified acute severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p = 0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p = 0.005], baseline albumin < 40g/l [HR: 9.5; 95% CI: 1.3-71.4; p = 0.026], and infliximab concentration at Week 2 < 16.5 μg/ml [HR: 5.6; 95% CI: 1.1-27.8; p = 0.034] as independent predictors of colectomy. Regarding patients who continued on biologicals after PNR to infliximab, there was a marginally higher cumulative probability for relapse in patients switching to another anti-TNF agent compared with those swapping to vedolizumab [p logrank = 0.08].

CONCLUSIONS:

About half of UC patients with PNR to infliximab will undergo colectomy. Patients with severe inflammation and low serum infliximab concetrations during the induction phase are at greatest risk.

• Authors: Konstantinos Papamichael, Oliviane Rivals-Lerebours, Thomas Billiet, Niels Vande Casteele, Ann Gils, Marc Ferrante, Gert Van Assche, Paul J Rutgeerts, Gerassimos J Mantzaris, Laurent Peyrin-Biroulet, Severine Vermeire
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 10 Issue 9 Pg. 1015-23 (Sep 2016) ISSN: 1876-4479 [Electronic] England
• PMID: 27022161 (Publication Type: Journal Article, Multicenter Study, Observational Study)
• Copyright: Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Gastrointestinal Agents
• Infliximab

Topics

• Adult
• Colectomy
• Colitis, Ulcerative (blood, drug therapy, surgery)
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• Gastrointestinal Agents (blood, pharmacokinetics, therapeutic use)
• Humans
• Induction Chemotherapy
• Infliximab (blood, pharmacokinetics, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Proportional Hazards Models
• Recurrence
• Retrospective Studies
• Risk Factors
• Treatment Failure