PROACTIVE THERAPEUTIC DRUG MONITORING MAY REDUCE THE NEED FOR COMBINATION THERAPY IN INFLAMMATORY BOWEL DISEASE PATIENTS TREATED WITH INFLIXIMAB

Abstract Background Combination therapy with an immunomodulator [IM] is recommended by ECCO guidelines for patients with moderate-to-severe inflammatory bowel disease (IBD) treated with infliximab [IFX]. Combination therapy reduce anti-drug antibody (ATI) formation. Maintenance of adequate trough IFX levels is also known to reduce ATI formation. Methods We hypothesised that the use of proactive TDM in patients receiving IFX monotherapy would result in equivalent therapy outcomes compared with patients receiving IFX in combination with an immunomodulator. A pilot study using proactive TDM was undertaken at our unit with IFX and ATI levels, assessed at trough, in all IBD patients receiving IFX. We retrospectively evaluated the outcome of proactive IFX TDM on IFX therapy outcome. Baseline demographics, IFX dosing schedules and use of concomitant immunomodulators were documented. The study primary endpoint was time to infliximab discontinuation in IFX monotherapy and combination therapy groups. Results 109 IBD patients receiving IFX with proactive TDM assessment were included. Median age, 36 years, 46% were female and, 36% UC., 37% and, 67% of patients were receiving IFX combination and monotherapy respectively. There was no significant difference in mean time to drug discontinuation between IFX combination and monotherapy groups, 2.33 [95% CI, 2.2–2.5] versus, 2.32 [95% CI, 2.0 –, 2.6] years respectively, p = 0.63. ATI concentrations [median] did not differ significantly between IFX combination and monotherapy groups, 2.9 AU/mL versus, 11.6 AU/mL, p = 0.54. In a multivariate analysis disease activity [p=0.005], low IFX levels [p=0.01] and elevated ATIs [p=0.001] were all independently associated with IFX discontinuation. There was no association between the use of IFX combination therapy and rates of IFX discontinuation, p=0.42. Conclusion Infliximab persistence, which is a proxy for successful therapy outcome, was similar in IFX monotherapy and combination therapy groups when proactive TDM was utilised. In the absence of concomitant immunomodulatory therapy, proactive TDM may improve IFX monotherapy outcomes, by maintaining higher IFX concentrations.