Background: Secondary loss of response to infliximab (IFX) or adalimumab (ADA) is common in inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) identifies patients with sub-therapeutic drug levels who are more likely to respond to dose intensification. Delivering dose-intensified therapy is resource-intensive and may benefit from a non-conventional decision making system such as a virtual clinic (VC). We sought to determine whether enrolment in a VC following a “treat-to-target” paradigm was effective in controlling disease activity in this complex cohort of patients.
Methods: Observational study of 37 IBD patients with secondary loss of response referred to our VC between September 2013-October 2016. Dose-intensification involved shortening the interval between ADA and IFX administration to weekly or six-weekly, respectively. Patients were reviewed in our VC every 6 months with scheduled C-reactive protein (CRP), faecal calprotectin (FC), intestinal ultrasound and IFX/ADA TDM using a drug-sensitive ELISA. Response was defined as maintaining improvements in biomarkers and physician global assessment for ≥12 months after initiation of intensified therapy, including those subsequently de-escalated to standard dosing. Patients failing intensified therapy were defined as non-responders. Receiver-operator characteristic analysis was performed to identify a threshold delta increase in drug level associated with response.
Results: 86% had Crohn's disease; 62% were treated with IFX. 22 (59%) responded, 55% of whom received IFX. 11 (30%) responders were de-escalated to standard dosing (median 12 months). 15 (41%) were non-responders (median 9 months). Considering the entire cohort, FC and CRP decreased after 12 months compared to baseline (450 vs. 80μg/g; p=0.019 and 8.5 vs. 3.5mg/L; p=0.004, respectively). Subgroup analyses of biomarker and TDM are shown in Table 1. Increasing IFX drug level >3μg/mL from baseline best predicted response (area under curve 0.86, sensitivity 80, specificity 78%). No threshold was found for ADA.
Conclusions: A novel virtual clinic model to deliver intensified anti-TNF therapy enabled recapture of response in the majority of patients, with almost one-third de-escalated to standard dosing. IFX drug levels increased in responders compared with non-responders and a threshold increase of >3μg/mL from baseline was associated with response. Non-responders treated with ADA showed similar increases in drug level to responders, suggesting that outcome was independent of ADA levels.