P387 Infliximab therapeutic drug monitoring test validated for measuring CT-P13 and SB2 biosimilars

Abstract

Promonitor®-IFX test is routinely used to monitor IBD patients treated with infliximab (IFX) including biosimilars1,2; and is the only in vitro diagnostics CE-marked kit validated by Janssen.3 It provides support to clinicians in their use of therapeutic drug monitoring (TDM) to understand patients’ drug and anti-drug antibody results relative to published data from clinical trials of Remicade® (Janssen/Merck, RMC)3. Here we validate the suitability and performance of Promonitor-IFX test for quantifying biosimilars CT-P13 (Remsima®/Inflectra®, Celltrion/Hospira) and SB2 (Flixabi®, Biogen) in comparison to RMC. The study sets the minimum basis of how a rigorous study to compare performance of a TDM immunoassay applied to reference and biosimilar biological drugs should be designed. The validation study was in accordance with the requirements established in the Clinical and Laboratory Standards Institute (CLSI) guidelines EP17-A2 (lower limit of quantification, LLOQ) and EP10-A3 (imprecision and bias). CLSI guidelines set a standard for the diagnostic industry accepted by all regulatory agencies. LLOQ was determined with 4 independent human serum matrices per each of 3 low-level IFX concentrations (0.175, 0.200 and 0.225 μg/ml), replicated 3 times per 2 lots of Promonitor-IFX (Progenika, Spain) for each drug CT-P13, SB2 and RMC over 3 days by one operator. Imprecision was evaluated using 3 replicates of 5 human serum matrices representative of clinically relevant IFX concentrations and spanning the measurement range of the test, run on one instrument with one kit lot by one operator over 6 non-consecutive operating days and one run per testing day (acceptance criteria of CV%<20%). LLOQ to quantify CT-P13, SB2 and RMC are identical: 0.27, 0.28, and 0.27 μg/ml, respectively. LLOQ values meet accuracy goal proposed based on total error <25%. The imprecision of Promonitor-IFX calculated by estimating the components of variance due to within-run and between-day factors meet the accuracy goals proposed at all levels of SB2 vs. RMC (CV% 6–13%), and of CT-P13 vs. RMC (CV% 5–7%). The bias study showed that the test can equally measure the active moiety IFX either in RMC or CT-P13 or SB2. The test is able to quantify SB2 in the measurement range of 0.57 to 13.1 μg/ml with a bias estimate of −1.369 to 0.105 μg/ml and an overall imprecision of 7% to 13%, and CT-P13 in the measurement range of 1 to 17 μg/ml with an overall imprecision of 5% to 7%. The measurement range includes the accepted clinical decision points. This study demonstrates that Promonitor-IFX test can equivalently measure either the reference IFX drug or any of the approved biosimilars CT-P13 or SB2 with the same sensitivity, precision and accuracy. 1. Fiorino G. Letter: Immunogenicity of infliximab originator vs. CT-P13 in IBD patients. Aliment Pharmacol Ther, 2017;46:903–5. 2. Fiorino G. Full interchangeability in regards to immunogenicity between the infliximab reference biologic and biosimilars CT-P13 and SB2 in inflammatory bowel disease. Inflamm Bowel Dis, 2017 (in press). 3. Marini JC. Comparisons of serum infliximab and antibodies-to-infliximab tests used in inflammatory bowel disease clinical trials of remicade(r). AAPS J, 2017;19:161–71.