Background: Virtual biologics clinics (VBC) are used in Leeds to review annually all patients receiving biological therapy and those who have lost response or had treatment complications. Decisions on continuing, switching or stopping therapy are documented based review of clinical symptoms, disease history and laboratory investigations Therapeutic drug monitoring (TDM) of infliximab trough levels (ITL) and anti-drug antibodies (ADA) can aid decision making but has previously not been universally available in the UK. The aim of this study was to assess whether access to therapeutic drug and antibody levels influences decision making within the VBC.
Methods: All IBD patients receiving Infliximab maintenance therapy were reviewed and two treatment decisions were recorded. The first decision was based on assessment of all clinical details but clinicians remained blinded to ITL and ADA data (Biohit assay). After documenting the first decision an administrator then revealed the ITL and ADA data and clinicians formed a second decision incorporating TDM data. Decisions were standardised to the following format: A – continue without change B – shorten infusion interval/increase infliximab (IFX) dose C – lengthen infusion interval D – stop IFX E – other.
Results: Of 201 patients reviewed TDM data were available for 191 (mean 40y old, 57% male). Diagnoses were Crohn's disease in 160, ulcerative colitis in 18 and IBD-U in 13 cases. Mean duration of IFX treatment was 4 years (minimum 6 months), 57% received combination therapy with an immunomodulator and 38% were on shortened infusion intervals. Disease activity was remission in 70%, mild in 19%, moderate in 10% and severe in 1%.
ITL were sub-therapeutic in 25% (<1.8 mg/l), therapeutic in 61% and supra-therapeutic in 14% (>7 mg/l); mean ITL was 3.85 mg/l. ADA were detected in 30% and were >50 AU/ml in 14%. Blinded treatment decisions were changed on unblinded review of ITL and ADA in 56 cases (29%, see table 1, chi-square test: p<0.0001). https://planner.smart-abstract.com/ecco2017/submission/en/abstract/3000/content# Knowledge of ITL & ADA led to 7 patients receiving higher dose IFX or more frequent infusions whereas 33 patients where able to dose de-escalate or stop IFX therapy.
Conclusions: TDM has a significant impact on decision making in VBC. Basing decisions on TDM rather than clinical acumen alone led to change in 29% of cases. Notably, an additional 23 patients (11% of the IFX-treated cohort) discontinued therapy due to undetectable ITL and high ADA. This represents a considerable cost saving and reduces the exposure of patients to potentially toxic therapies with no ongoing therapeutic benefit. Routine TDM should be considered as an integral part of the annual biologics assessment