Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics

Background The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).Methods This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.Results This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 mu g/mL (2.1, 7.8) vs 5.9 mu g/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.Conclusions This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX. This study compared the pharmacokinetics of infliximab combination therapy with azathioprine vs infliximab with proactive therapeutic drug monitoring as monotherapy among pediatric patients with Crohn's disease within the first 22 weeks. No pharmacokinetic differences were found between monotherapy and combination therapy.