P0936 Switch from intravenous to subcutaneous infliximab: first subcutaneous dose and cumulative area under curve
Authors: Padulles-Zamora N , Cleries Rovira P , Alonso Moreno M , Rodriguez Moranta F , Ruiz Cerulla A , Rodriguez Alonso L , Muñoz Bolaño M , Guardiola Capon J 
Published: January 2025

Background

The drug development assessment report of subcutaneous infliximab (SC-IFX) indicates that dosing is aimed to establish a similar area under curve (AUC) value to that of label dosing. In addition, a SC-IFX concentration (Cp) cut-off associated with deep remission of 20 mg/L has been proposed (1). A percentage of the patients receive escalated IV dosing and there are no clear recommendations for an optimal time to switch from IV-IFX to SC-IFX, nor regimens that result in a similar cumulative AUC for different body weights to avoid underexposure.

Aims

- Determine when Cp are 20 mg/L in different IV-IFX scenarios to guide switch to SC-IFX

- Evaluate Cmin at week 54 (Cmin,54w) after the switch to SC-IFX

- Compare AUC before and after the switch to SC-IFX in patients receiving 8 weekly IV-IFX

Methods

Virtual patients (30-110 kg) received IV-IFX (5-10 mg/kg/4-8 weeks (Q4-8W) and switched to SC-IFX 120 and 240 mg/two weeks (Q2W). 1000 Monte Carlo simulations were carried out for each scenario from a previously published population pharmacokinetic model (2) using the nonlinear mixed effects modelling approach implemented in NONMEM v.7.4®. The results were analysed with R v.4.2.0.

Results

When switching from IV-IFX Q8W to SC-IFX at the end of the interval, Cp were &lt;12 mg/L in all scenarios. None of the scenarios achieved Cp&gt;20 mg/L at week 6. At week 4, nearly all patients receiving 7-10 mg/kg reached Cp&gt;20 mg/L. For regimens Q4W the Cp&gt;20 mg/L objective was attained for ≥8mg/kg. For ≥9mg/kg Q6W and weights over 50 Kg, Cp&gt;20 mg/L was also obtained. At week 3 after the last infusion, all scenarios accomplished a Cp&gt;20mg/L (Table 1).

The Cmin,54w were &gt;12 mg/L in all scenarios except for 120 mg Q2W and body weight ≥90 kg. The Cmin,54w were &gt;20 mg/L in patients receiving 120 mg Q2W and weighting 30 kg and on a 240 mg Q2W in patients weighting 50-90 kg. For weights over 110 kg, Cmin,54w&gt;20 mg/L was not attained. The AUCss8w for SC-IFX 240 mg Q2W was superior to IV-IFX in all scenarios on patients weighting 30-50 kg, in patients on 5-7 mg/kg Q8W and 70 kg and in patients on 5-6 mg/kg Q8W and 90 kg. Tthe AUCss8w for SC-IFX 120 mg Q2W was only superior to IV-IFX 5-8 mg/kg Q8W in patients weighting 30 kg and 5 mg/kg Q8W in patients weighting 50 kg (Table 2).

Conclusion

Switching IV to SC when IFX concentrations are 20 mg/L, and not below, may decrease the risk of temporary underexposure, thus achieving steady state much faster. This usually falls halfway between two infusions. A Cmin,54w &gt;20 mg/Lwas attained only in patients weighting &lt;110 kg and receiving 240 mg Q2W. Switching to SC-IFX 240 mg Q2W resulted in a higher AUCss8w than IV-IFX Q8W in all scenarios in patients weighting ≤50 kg and in patients receiving 5-6 mg/kg and body weight 70-90 kg.

References

1.Roblin X et al., Higher serum infliximab concentrations following subcutaneous dosing are associated with deep remission in patients with inflammatory bowel disease. J Crohns Colitis. 2023 Nov 2:jjad188.

2.Schreiber S et al., Randomized controlled trial: subcutaneous vs intravenous infliximab CT-P13 maintenance in inflammatory bowel disease. Gastroenterology. 2021;160(7):2340-2353