Abstract Background Intravenously applied infliximab (IFX) is commonly used for Inflammatory Bowel Disease (IBD) treatment. Recently, subcutaneous (SC) flat-dose IFX biosimilar was introduced offering potential advantages over intravenous (IV) weight-based dosing. Prospective pharmacokinetic-data and clinical outcomes in IBD practice are scarce, since drug approval was primarily based on a rheumatoid-arthritis study-population concomitantly using methotrexate. The main objective of this prospective study was to compare IFX exposure and clinical outcomes when switching IV to SC IFX therapy in IBD remission patients, also addressing the effect of concomitant immunomodulators. Methods In this single-centre, prospective study, 38 adult IBD patients in clinical remission on a 6-8 weekly IFX IV-dosing interval were switched to biweekly dosed SC IFX and followed for 24 weeks. The primary endpoint was the comparison between Area Under the Concentration-time curves (AUCs) at steady state before and after switching. AUCs were calculated using MwPharm ++ (version 2.4.0; Hanzel 2021).1 Secondary endpoints included trough levels, generation of anti-drug antibodies (ADAbs), time burden for application, and quality of life (IBDQ-NL). Additionally, twelve-month trough levels were compared across IFX monotherapy, combination, and thiopurine-discontinuation groups. Results A total of 35 patients were evaluated, of whom 20 received IFX monotherapy and 15 received IFX combination therapy. The cohort comprised 11 patients with ulcerative colitis and 24 with Crohn’s disease. Mean AUCs6-8 weeks were comparable between IV and SC administration 27,662 ± 7,116 mg·h/L vs 29,320 ± 10,505 mg·h/L (p = 0.278), independent of immunomodulator use (table 1). IFX trough levels increased on SC IFX (median [IQR 4.6 3.0-6.1 mg/L vs 16.1 11.6–20.6 mg/L, p 0.001), independent from immunomodulator use p = 0.347. These results were consistent at month 12, regardless of continued monotherapy, combo, or withdrawal of thiopurines at month 6. Time burden decreased substantially (median reduction 9,3 hours/6 months, p 0.001) and IBDQ-NL score increased (189 to 197, p = 0.01). ADAbs were detected in 9% without clinical impact. During the follow-up period, no patient had an exacerbation or required escalation of treatment. The percentage still being treated with IFX SC after 6 months was 97%. Conclusion Switching from IV to SC IFX in quiescent IBD patients maintained equivalent drug exposure with higher trough levels, without a higher risk of ADAb formation, reduced considerably time of application and improved quality of life, regardless of immunomodulator co-use. Reference: 1 Hanzel J, Bukkems LH, Gecse KB, D’Haens GR, Mathôt RAA. Population pharmacokinetics of subcutaneous infliximab CT-P13 in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2021 Nov;54(10):1309-1319. Doi: 10.1111/apt.16609. Conflict of interest: Ms. Van Dinter-Van De Ven, Lieke: No conflict of interest Romberg - Camps, Marielle J.L.: No conflict of interest Wong, Dennis: No conflict of interest Van Bodegraven, Adriaan Anthonie: No conflict of interest Boone, Niels: No conflict of interest
Ven et al. (Thu,) studied this question.