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.

Keywords: Crohn’s disease; IBD; adalimumab; infliximab; ulcerative colitis.

FIGURE 1.

Bar graphs comparing percentage of patients in (A) sustained clinical remission between 22 and 52 weeks (SCR22-52) and (B) sustained clinical and biochemical remission between 22 and 52 weeks (SCBR22-52) between pre-TDM and post-TDM groups.

FIGURE 2.

Kaplan-Meier curve comparing (A) time to high concentration antidrug antibody (ADA) development, (B) time to cessation of initial anti-TNF drug, and (C) time to cessation of initial anti-TNF drug related to any detectable ADA between pre-TDM and post-TDM groups.

FIGURE 3.

Process control chart depicting the monthly percentage of patients in the practice in sustained clinical remission, centerline (mean monthly percentage in sustained clinical remission), and control limits (3x SD). Chart is annotated with timing of interventions related to the TDM QI initiative.