Forecasted infliximab concentrations during induction predict time to remission and sustained disease control of inflammatory bowel disease - 17/05/24
, Marla C. Dubinsky b, Shervin Rabizadeh c, John C Panetta d, Elisabeth A. Spencer b, Erwin Dreesen a, Geert D'Haens e, Thierry Dervieux f, David Laharie g, ⁎ Highlights |
• | There is a need to improve the outcome of patients with inflammatory bowel disease treated with anti-TNF. |
• | A Bayesian pharmacokinetic tool disease was developed to forecast infliximab concentrations during induction of remission. |
• | Higher forecasted infliximab during induction associated with better disease control during maintenance. |
• | Dosing optimization using Bayesian pharmacokinetic tool can help improve outcome of inflammatory bowel disease. |
Abstract |
Background |
Infliximab (IFX) exposure is established as a predictive factor of pharmacokinetic (PK) origin in inflammatory bowel disease (IBD), and expert consensus is to achieve adequate exposure during induction to achieve and sustain remission.
Methods |
We retrospectively evaluated the performance of a Bayesian PK tool in IBD patients starting IFX. Trough IFX serum levels collected immediately before the third (at week 6) and fourth (at week 14) infusions were evaluated from 307 IBD patients (median age=17 years, 50 % females, 83 % with Crohn's disease). Forecasted IFX concentration at the fourth infusion were estimated using serum IFX, antibodies to IFX, albumin and weight determined immediately before the third infusion using population PK calculator with Bayesian prior. The outcome variable was a clinical & biochemical remission status achieved (CRP levels below 3 mg/L in presence of clinical remission). Statistics consisted of Kaplan Meier analysis with calculation of Hazard ratio (HR), and logistic regression.
Results |
IFX concentration above 15 µg/mL immediately before the third infusion associated with shorter time to clinical & biochemical remission than concentration below 15 µg/mL without reaching significance (163±14 days vs 200±16 days, respectively; p=0.052). However, using PK parameters at the third infusion, forecasted IFX concentrations above 10 µg/mL immediately before the fourth infusion were significantly associated with a higher rate (HR=1.6 95 %CI: 1.1 to 2.1 p<0.01) and shorter time to remission (148±18 days vs 200±13 days p<0.01). In the presence of IFX concentration above 15 µg/mL at the third infusion, there was a significant 2.5-fold higher likelihood of sustained clinical & biochemical remission status during maintenance as compared to IFX concentrations below 15 µg/mL (p<0.01). Forecasted IFX level above 10 µg/mL at fourth infusion associated with significantly 3.9-fold higher likelihood of clinical & biochemical remission as compared to forecasted IFX concentrations below 10 µg/mL (p<0.01).
Conclusions |
These data further support that optimized IFX concentrations during induction are associated with enhanced disease control in IBD.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Infliximab, Therapeutic drug monitoring, Inflammatory bowel disease
Abbreviations : TDM, IBD, CD, UC, PK, IFX, ATI, TNF-α, CRP, V1, V2, Q, HR, Cl, HMSA, CDAI, LR, OR, PPV, NPV
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Vol 48 - N° 6
Articolo 102374- Giugno 2024 Ritorno al numero
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