Population pharmacokinetics of subcutaneous infliximab CT-P13 in Crohn's disease and ulcerative colitis

Background Infliximab is a chimeric monoclonal antibody against tumour necrosis factor-alpha for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of CT-P13, an infliximab biosimilar, was approved for clinical use. Aims To characterise CT-P13 pharmacokinetics (PK) and its clinically relevant determinants after subcutaneous administration through population PK modelling. Methods Data from a two-part Phase I study with intravenous (5 mg/kg) and variable maintenance subcutaneous dosing of CT-P13 with frequent PK sampling in patients with CD or UC were used. Population PK analysis was conducted by non-linear mixed effects modelling. Covariates affecting PK parameters were chosen based on their clinical relevance (effect size of >= 20%) using a full fixed-effect modelling approach. Results CT-P13 PK was described by a two-compartment model with linear elimination. The half-life in a typical 70 kg patient with serum albumin of 44 g/L was 10.8 days. The typical value for clearance was 0.355 L/d, absorption constant 0.273/d, bioavailability 79.1%, central volume of distribution 3.10 L and peripheral volume of distribution 1.93 L. Clinically relevant covariates affecting clearance were body weight (+43.2% from 70 to 120 kg), the presence of anti-drug antibodies (+39%) and serum albumin concentration (+30.1% from 44 to 32 g/L). Simulated drug exposure was comparable between routes of administration for patients weighing 50 or 70 kg, but lower with subcutaneous dosing in patients weighing 120 kg. Conclusions This first population PK model for subcutaneous CT-P13 supports fixed subcutaneous maintenance dosing, although heavy patients had lower cumulative drug exposure.