Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease—Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics

Abstract

CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn’s disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD.

Long‐term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel disease treated with intensified doses: The REMSWITCH‐LT study

“…It is consistent with the available real-world data reporting a rate of treatment discontinuation in less than 8%. 17,28 In addition, the risk of safety is acceptable as we did not observe any severe adverse events or adverse event leading to therapeutic discontinuation. In addition, only 7% and 5.4% of patients experienced mild and transient erythema or pain at injection site, respectively.…”

“…It seems conflicting with a recent review considering that amongst patients requiring dose-intensified SC infliximab, higher doses given fortnightly may achieve greater drug level increments than shortening the interval using standard 120 mg dosing. 28 In a subgroup of 50 patients on prior dose-intensified IV infliximab from uncontrolled real-world data, patients who switched to SC IFX with a shortened dosing interval of 120 mg weekly had similar serum drug levels compared to those switching to 120 mg every 2 weeks at each time point despite comparable objective biomarker of disease activity. 17 Furthermore, 120 mg every 2 weeks dosing was not associated with higher infliximab serum levels than every week injections in a multivariable model of linear regression analysis.…”

Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy

“…Potential great advantages in terms of patient convenience with lower rates of work/school absenteeism, decrease in health care pressure, and reduction in carbon footprint are unquestionable with estimated comparable drug costs (7,8,16). However, limits concerning patient compliance and new pharmacokinetic profile should be carefully evaluated and although have not been highlighted in this work replication is needed for further reassurance on this (17).…”

“…As demonstrated by Schreiber et al (10), drug trough levels do not adequately reflect total drug exposure, with the “area under the curve” (AUC) a more suitable tool to evaluate drug exposure in intravenous and subcutaneous regimens. Consequently, since the best pharmacokinetics predictors for IFX efficacy are still uncertain, a purposeful interpretation of these elevated IFX trough drug levels is required together with the eventual definition of new specific therapeutic concentration targets (17). In the study from Buisson et al (12) not only reduced, but also stable IFX trough levels after the switch were significantly associated with relapses during follow‐up, implying that higher IFX concentrations may be required to achieve the same efficacy.…”

Real-World Study on Vedolizumab Serum Concentration, Efficacy, and Safety after the Transition from Intravenous to Subcutaneous Vedolizumab in Inflammatory Bowel Disease Patients: Single-Center Experience

“…Although studies consistently show elevated trough levels of subcutaneous vedolizumab, the clinical significance of higher trough concentrations is not yet clear. Subcutaneous drugs have lower bioavailability, lower peak concentrations, and differences between peak and trough concentrations are smaller [ 18 ]. Therefore, two formulations cannot be directly compared.…”