P767 Pharmacokinetics of subcutaneous infliximab induction and maintenance in patients with moderate-to-severely active Crohn’s disease

Abstract

Abstract Background Since 2021, subcutaneous (SC) infliximab (IFX) has been available for maintenance treatment of Crohn’s disease (CD) after an induction phase of 2 intravenous administrations of 5 mg/kg. The DIRECT-CD study is an ongoing randomised multicentre trial in which CD patients receive SC IFX also during induction. The applied SC IFX doses in the DIRECT-CD are based on population pharmacokinetics derived during maintenance treatment with SC IFX. We aimed to validate our induction regimen and correlate serum concentrations with clinical efficacy. Methods Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) >220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at week 0 and 2, followed by maintenance treatment (120 mg every other week). IFX serum concentrations and CDAI were evaluated at week 2, 4, 8, 14 and 26. Clinical remission was defined as a CDAI ≤150. For this analysis, body weight is defined as low if <80 kg and high if ≥80 kg. Results In total, 48 samples of 12 Crohn’s disease patients were analysed (Table 1). During the induction phase (week 2 and 4), observed IFX serum concentrations were lower than expected by the population pharmacokinetic model for all patients (median 15.0 µg/mL [IQR 9.4-20.0]). Moreover, concentrations were significantly lower in patients with a low versus high body weight (median 20.0 µg/mL [IQR 15.0-21.0] vs median 10.2 µg/mL [IQR 4.4-15.8], resp., P=0.004). During the maintenance phase (week 8, 14 and 26), median IFX serum concentrations were also higher in patients with a low body weight compared to patients with a high body weight (17.5 µg/mL [IQR 14.8-19.5] vs 8.9 µg/mL [IQR 5.8-13.8], P<0.001). No patients in the first quartile of IFX serum concentrations (≤7.0 µg/mL) at week 2 reached clinical remission at Week 8, whereas all patients who had an IFX serum concentration at week 2 of ≥15.0 µg/mL reached clinical remission at week 8. At the end of the study (week 26), clinical remission was reached in 67% of patients with a low body weight whereas only 33% of patients with a high body weight reached clinical remission. Conclusion These data implicate the importance of body weight in SC IFX dosing strategies. Based on these findings, SC IFX induction and maintenance treatment is changed to a weight-based dosing scheme in the ongoing DIRECT-CD trial.