TY - JOUR
T1 - Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics
AU - Colman, Ruben J.
AU - Vuijk, Stephanie A.
AU - Mathot, Ron A. A.
AU - Van Limbergen, Johan
AU - Jongsma, Maria M. E.
AU - Schreurs, Marco W. J.
AU - Minar, Phillip
AU - de Ridder, Lissy
AU - D'Haens, Geert R. A. M.
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Oxford University Press on behalf of Crohn's & Colitis Foundation. All rights reserved.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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 μg/mL (2.1, 7.8) vs 5.9 μg/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.
AB - 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 μg/mL (2.1, 7.8) vs 5.9 μg/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.
UR - http://www.scopus.com/inward/record.url?scp=85195462362&partnerID=8YFLogxK
U2 - 10.1093/ibd/izad307
DO - 10.1093/ibd/izad307
M3 - Article
C2 - 38167922
SN - 1078-0998
VL - 30
SP - 1678
EP - 1685
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 10
ER -