OP007 A multi-centre double blind randomised placebo-controlled study of the use of rectal tacrolimus in the treatment of resistant ulcerative proctitis

Abstract

The Trough Concentration Adapted Infliximab Treatment (TAXIT) randomized controlled trial [1] showed that targeting patients' infliximab trough concentrations in a 3-7 g/mL window resulted in a more efficient use of the drug in patients with inflammatory bowel disease (IBD). However, following dose optimization, continued concentration-based dosing was not superior to clinicallybased dosing for achieving a co-primary endpoint of clinical and biological remission after 1 year. Methods: This was a retrospective analysis of the long-term outcome of all 226 patients who completed the TAXIT maintenance phase. Durability of response to infliximab was correlated with serum trough concentrations and important quality of care outcome parameters, including need for IBD-related hospitalization, need for abdominal surgery and steroid use. Results: With a median follow-up of 41 months after the completion of the TAXIT trial, 167/215 (78%) patients were still on continued treatment with infliximab, and 48/215 (22%) patients needed to stop (11 patients were lost to follow-up). Among the 48 patients who discontinued infliximab, 10/27 (37%) randomized previously to the clinically-based dosing arm did so within 1 year, compared to 2/21 (10%) patients randomized to the concentration-based dosing arm (p<0.05). Among the 167 patients who continued infliximab, the dosing scheme was intensified in 56 patients and de-intensified in 27 patients, compared to the end of the TAXIT maintenance phase. Median trough concentrations of infliximab at the end of follow-up were 4.73 g/mL (IQR=3.3-6.42). Five patients developed immunogenicity within 1 year after TAXIT and all had been randomized to the clinically-based dosing arm. In patients continuing on infliximab, the rates of IBD-related hospitalization (16/167 patients or 9.6%), abdominal surgery (4/167 patients or 2.4%) and steroid use (6/167 patients or 3.6%) during the entire follow-up period were very low and significantly better than in patients who had to discontinue infliximab.