Table 3.
Randomized controlled trials regarding the role of therapeutic drug monitoring in IBD.
| RCT acronym |
IBD type |
Study arms | Primary end point | Major limitations |
|---|---|---|---|---|
| Infliximab | ||||
| N/A97 | CD | Reactive TDM vs. empiric dose optimization | Cost-effectiveness and CDAI response after 12 weeks | - IFX TC to target of 0.5 μg/mL |
| TAXIT9 | CD / UC | Proactive TDM vs. clinically based dose optimization | Clinical and biochemical remission at one year after optimization phase | - All patients were optimized based on IFX TC, prior to randomization that may eliminated the opportunity for proactive TDM to prove its benefit - IFX TC to target 3-7 μg/mL - Only one year follow up |
| TAILORIX98 | CD | Dose optimization based on clinical symptoms and biomarkers and/or proactive TDM vs. dose optimization based on clinical symptoms alone | Sustained CS-free clinical remission from weeks 22 to 54 with no ulcers at week 54 | - IFX TC to target of 3 μg/mL - IFX dose in the ‘TDM’ arms could be escalated based also on symptoms and biomarkers - IFX dose in the ‘control’ group could be escalated based only on clinical symptoms and as a result a high number of dose optimizations were driven by nonspecific symptoms as demonstrated by normal drug and biomarker levels in these patients - IFX concentrations were similar in all 3 groups which likely accounted for the similar efficacy outcomes - Sustained IFX TC of >3μg/mL in <50% in the ‘TDM’ arms |
| PRECISION99 | CD / UC | Proactive TDM based on PK dashboard driven dosing vs. standard dosing | Sustained clinical remission after 1 year |
- IFX TC to target ≥ 3 μg/mL - No dosing adaptations were allowed in the control group - Lack of endoscopic outcomes |
| Adalimumab | ||||
| PAILOT10 | CD* | Proactive vs. reactive TDM | Sustained CS-free clinical remission from weeks 8 to 72 | - ADM TC to target ≥ 5 μg/mL - Lack of endoscopic endpoints - Rather small sample size |
*
Pediatric.
TAXIT: Trough Concentration Adapted Infliximab Treatment; TAILORIX: A Study investigating Tailored Treatment With Infliximab for Active Crohn’s Disease; PRECISION: Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab; PAILOT: Pediatric Crohn’s Disease Adalimumab Level-based Optimization Treatment; RCT: randomized controlled trial; IBD: inflammatory bowel disease; N/A: not applicable; CD: Crohn’s disease; UC: ulcerative colitis; CS: corticosteroids; TDM: therapeutic drug monitoring; TC: trough concentration; PK: pharmacokinetic; CDAI: Crohn’s disease activity index; IFX: infliximab; ADM: adalimumab.