Effect of a Practice-wide Anti-TNF Proactive Therapeutic Drug Monitoring Program on Outcomes in Pediatric Patients with Inflammatory Bowel Disease

Abstract

Background Reports on the feasibility and effectiveness of translating proactive, antitumor necrosis factor (TNF) therapeutic drug monitoring (TDM) for inflammatory bowel disease into practice-wide quality improvement (QI) are lacking. We aimed to determine whether a TDM QI program improved outcomes at a large academic pediatric gastroenterology practice. Methods We instituted local anti-TNF TDM practice guidelines to proactively monitor and optimize drug levels (goal >5 μg/mL). We conducted a retrospective single-center cohort analysis of patient outcomes before (pre-TDM) and after (post-TDM) guideline institution and assessed the independent effect by multivariable regression. Primary outcome was sustained clinical remission (SCR22-52), defined as physician global assessment (PGA) of inactive from 22 to 52 weeks and off corticosteroids at 52 weeks. Results We identified 108 pre-TDM and 206 post-TDM patients. The SCR22-52 was achieved in 42% of pre-TDM and 59% of post-TDM patients (risk difference, 17.6%; 95% CI, 5.4–29%; P = 0.004). The post-TDM group had an increased adjusted odds of achieving SCR22-52 (odds ratio, 2.03; 95% CI, 1.27–3.26; P = 0.003). The adjusted risk of developing high titer antidrug antibodies (ADAs) was lower in the post-TDM group (hazard ratio, 0.18; 95% CI, 0.09–0.35; P < 0.001). Although the risk of anti-TNF cessation for any reason was not significantly different, there was a lower adjusted risk of cessation related to any detectable ADA in the post-TDM group (hazard ratio, 0.45; 95% CI, 0.26–0.77; P = 0.003). Conclusions A practice-wide proactive anti-TNF TDM QI program improved key clinical outcomes at our institution, including sustained clinical remission, incidence of high titer ADA, and anti-TNF cessation related to ADA.

Antibodies‐to‐infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn’s disease

“…37 While paediatric IFX monotherapy is not yet supported in the European ECCO-ESPGHAN guideline, 10 proactive therapeutic drug monitoring with initial monotherapy is a common paediatric practice in other parts of the world including North America. 4,28,38 More studies, such as the REMODEL trial (clinicaltrials.org NCT04974099), are needed to determine if dose optimisation from the start of IFX and proactive therapeutic drug monitoring can improve drug durability and endoscopic healing. We recognise that while clinical and biochemical outcomes in our study were assessed, it was not feasible to perform the gold standard endoscopic evaluation to directly assess mucosal healing.…”

“…Although TNF‐alpha antagonists (anti‐TNF) have become one of the most effective medical treatments for inflammatory bowel diseases (IBDs), 1 low drug exposure can lead to anti‐drug antibody formation (immunogenicity) and increase the risk of infusion reactions or loss of response 2 . As standard (label‐guided) dosing with infliximab (IFX) monotherapy is associated with high rates of immunogenicity, 2 clinicians are left to decide between proactive therapeutic drug monitoring with IFX monotherapy, combination therapy (IFX and an immunomodulator), stratification of risk factors for immunogenicity with pharmacogenomics such as human leucocyte antigen (HLA) polymorphisms or a combination of these approaches to optimise efficacy and durability 3‐5 …”

Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

“…The proactive approach demonstrated a clear benefit with regard to corticosteroid-free clinical remission between weeks 8 and 72. A recent retrospective pediatric paper showed the benefit of a proactive anti-TNF TDM approach in improving outcomes related to steroid-free clinical remission ( 28 ).…”

Therapeutic drug monitoring in inflammatory bowel disease: At the right time in the right place

“…Pediatric IBD represents a special group of patients, where the limited therapeutic armamentarium and challenges in balancing drug safety and efficiency created a critical need for drug monitoring[ 21 ]. Pro-active TDM showed to increase corticoid-free clinical remission in children with CD treated with Adalimumab (ADL) compared with reactive monitoring (PAILOT study)[ 22 ] and sustained clinical remission in children with CD, ulcerative colitis or IBD-unclassified treated with either IFX or ADL therapy[ 23 ]. In addition, model outcomes indicated that proactive TDM vs reactive TDM for ADL may provide higher quality-adjusted life-years at lower cost in pediatric CD patients[ 24 ].…”