P609 A treat-to-target approach via a virtual clinic amongst inflammatory bowel disease patients with secondary loss of response to anti-TNF therapy improves clinical outcomes

Abstract

Introduction: Secondary loss of response to infliximab (IFX) or adalimumab (ADA) occurs in 30-40% of patients with inflammatory bowel disease (IBD).1 Drug monitoring identifies patients with sub-therapeutic drug levels that are more likely to respond to dose intensification (shortening interval or increasing dose). Delivering compassionate dose-intensified therapy is challenging and resource-intensive and may benefit from a nonconventional decision-making system such as a virtual clinic (VC). We sought to determine whether enrolment in a VC following "treat-to-target" goals (clinical response and biomarker normalisation) was effective in controlling disease activity in this complex subgroup of patients. Methods: We performed a retrospective observational study of IBD patients with secondary loss of response referred to the VC between September 2013 and May 2015. Dose-intensified patients were reviewed in the VC every 6 months with the results of biomarkers (C-reactive protein (CRP), faecal calprotectin, (FC)) and IFX/ADA drug levels to determine response to therapy and aid ongoing management decisions. Response was defined as achieving and maintaining improvements in biomarker and physician global assessment for >12 months following initiation of intensified therapy (including those subsequently de-escalated to standard dosing). Patients failing intensified therapy were defined as non-responders. Longitudinal data were analysed using Wilcoxon matched-pairs and inter- group comparisons with Mann-Whitney or chi-squared testing. Values are presented as median unless otherwise stated. Results: Forty-six of 52 (89%) patients referred were approved for intensified therapy. Forty (87%) had Crohn's disease, and 29 (63%) were treated with IFX. Two patients were excluded from further analysis due to noncompliance and 16 for completing <6 months of follow-up. Of the 28 patients with 12 months follow up, 18 (64%) were responders, of whom 9 successfully de-escalated to standard dosing after a median of 11 months. Ten (36%) were non-responders, 6 of whom switched to vedolizumab, 3 to clinical trial and 1 to the alternative anti-TNF agent after a median of 9.5 months. Considering the cohort as a whole, there were significant reductions in FC and CRP after 12 months (600 vs. 90 mug/g; p = 0.016 and 8 vs. 3 mg/L; p = 0.022) compared with baseline. FC and CRP were significantly higher in non-responders compared with responders and drug levels increased significantly in responders but not in non-responders (Table 1). Responders were significantly more likely to normalise CRP, FC and achieve therapeutic drug levels compared with non-responders (OR = 7.5; p = 0.019, OR = 60; p =<0.001, OR = 7; p = 0.046, respectively). Conclusion: Employing a novel virtual clinic service model to deliver compassionate intensified anti-TNF therapy was associated with recapture of clinical response in over 60% of patients enrolled for >12 months, with 30% successfully de-escalated back to standard dosing. Drug monitoring of IFX demonstrated a change in levels amongst responders compared with non-responders. Responders were more likely to normalise biomarkers and achieve therapeutic drug levels compared with non-responders, suggesting that a treat-to-target strategy is associated with improvements in measures of disease activity