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* = Presenting author

P375 Long-term outcomes after primary infliximab treatment failure in patients with inflammatory bowel disease

S. Buhl*, C. Steenholdt, M. Borghede, M. Rasmussen, J. Brynskov, O. Ø. Thomsen, M.A. Ainsworth

Copenhagen University Hospital, Herlev, Department of Gastroenterology, Herlev, Denmark

Background

Primary anti-tumour necrosis factor (TNF) treatment failure with infliximab (IFX) has been reported in about one-third of patients with inflammatory bowel disease (IBD). There is no consensus on how to handle these patients. This study primarily assessed the prognosis, defined as surgery-free survival, after primary IFX treatment failure. The secondary objective was to investigate first intervention after primary IFX failure, interventions applied within the first year, and resulting disease status.

Methods

Retrospective cohort study of all IBD patients treated with IFX as first-line TNF-inhibitor at a tertiary centre until end of 2014. Primary non-response was defined as no clinical improvement during IFX induction therapy resulting in discontinuation of IFX treatment.

Results

In total, 560 IBD patients received primary anti-TNF therapy with IFX. Amongst these, 81 (15%) had primary IFX treatment failure after a median of 3 IFX infusions, IQR 24. In Crohn’s disease (CD) patients, (n = 33; 41%) with primary IFX failure indications for IFX were luminal (61%) or fistulising disease (39%). In ulcerative colitis (UC) patients (n = 48; 59%) indications for IFX were pancolitis (54%), left-sided colitis (33%), or proctitis (13%). Half of the cohort of primary IFX treatment failures underwent major surgery related to disease flare at a median of 196 days after the first IFX infusion. There was a non-significant trend of shorter time to surgery in patients with UC (median 141 vs 260 days, p = 0.25). The first treatment applied after primary IFX failure was surgery (49%), switching to other TNF-inhibitor (15%), other biologic (2%), or initiation/optimisation of treatment with topical agents (14%), immunosuppressives (12%), or systemic steroids (10%). Risk of surgery immediately after primary IFX failure was significantly higher in patients with UC than CD (OR 3.1 [1.2–7.7], p = 0.02). One year after primary IFX treatment failure, a majority of 51 (63%) patients had undergone major IBD-related surgery (CD n = 19 (58%), UC n = 32 (67%); p = 0.49). Patients without surgery (n = 30; 37%) had been handled by initiation/optimisation of immunosuppressives (57%), topical treatment (40%), a second TNF-inhibitor (27%), other biologic (13%), and/or systemic steroids (23%). Amongst medically treated patients, 16 (53%) still had clinically active disease after 1 year.

Conclusion

IBD patients with primary IFX treatment failure have a poor therapeutic prognosis. After 1 year, two-thirds have undergone major IBD-related surgery, and more than half of medically treated patients still have active disease. Whether introduction of new biologics can improve prognosis for this population remains to be investigated.