Editorial: proactive anti-TNF drug monitoring in IBD—Ready for prime time?

Theoretically, proactive therapeutic drug monitoring (TDM) aims to prevent loss of response to therapy consequent to immunogenic or pharmacokinetic failure and reduce subsequent disease flares.¹ In doing so, it is hoped that this strategy will improve various disease outcomes, including treatment failure and need for inflammatory bowel disease (IBD)-related hospitalisation and surgery.

A recent meta-analysis including nine randomised controlled trials (RCTs) comparing a proactive strategy to conventional management of IBD patients treated with anti-tumour necrosis factor (TNF) agents reported no benefit of the proactive strategy in terms of clinical remission at 1 year (relative risk [RR]: 0.93; 95% confidence interval [CI]: 0.81–1.13).² Sethi et al have performed³ a systematic review and meta-analysis of studies including both RCT and prospective and retrospective cohort studies comparing proactive versus reactive TDM and proactive TDM versus standard of care (SOC). A broad range of clinical outcomes was assessed. Proactive TDM was associated with various benefits in terms of disease outcomes with significantly lower risk of treatment failure (defined as loss of response or treatment discontinuation) when compared to both SOC (RR: 0.64, 95% CI 0.48-0.85) and to reactive TDM (RR: 0.46, 95% CI 0.21-0.98). Finally, proactive TDM was associated with lower rate of IBD-related hospitalization compared to reactive TDM (RR: 0.33, 95% CI 0.21-0.54) and compared to SOC (RR: 0.64, 95 % CI 0.40-1.00) but was not associated with lower need of surgery (RR: 0.51, 95 % CI 0.25-1.02) compared to SOC. This novel meta-analysis is of paramount interest since it included a variety of studies, and analysed various clinical issues of interest from the point of view of both patients and physicians - such as the need for surgery or for hospitalisation.

Hence, is proactive TDM ready for prime time in clinical practice in IBD patients treated with anti-TNF therapy? Definitely not yet. First, results of the measurement of serum drug concentration should be obtained and adequately modified if needed in real time and not immediately prior to the next drug administration, as usually performed in both RCTs and routine practice. In this way, the point of care (POC) for TDM testing could play a key role in a proactive strategy. In addition, the best threshold values are not yet defined and may differ between POC and ELISA assays.⁴ Second, we need skill upgrades for gastroenterologists taking care of IBD patients to better interpret the results of TDM in their daily practice. Third, the optimal target of serum anti-TNF concentrations using TDM proactive strategy should also be better clarified. Indeed, Brandse et al⁵ have reported that insufficient infliximab drug exposure (below 3 μg/ml) was the most predictive factor for developing anti-drug antibodies (with a four-fold increase risk). Vande Casteele et al recently suggested that the best therapeutic infliximab levels should be higher than 5 μg/ml.⁶

Is there a window of opportunity to substantially improve the efficacy of a proactive TDM strategy using an i-Dose-assisted pharmacokinetic dashboard combined with proactive TDM to better drive dosing and maintain therapeutic drug levels? Results from the randomised, controlled, multicentre, open-label trial OPTIMISE (NCT04835506) are awaited.⁷

AUTHOR CONTRIBUTIONS

Xavier Roblin: Writing – original draft (equal). stephane nancey: Writing – original draft (equal).