Impacto de la monitorización proactiva de Infliximab y el empleo de su biosimilar CPT-13 en la enfermedad inflamatoria intestinal104

Abstract

Introduction Infliximab (IFX) is a monoclonal anti-TNFα antibody that has demonstrated its effectiveness in inflammatory bowel disease (IBD). However, between 10-40% of patients experience primary loss of response, and 20-40% experience secondary loss of response. There is increasing evidence of the utility of proactive therapeutic drug monitoring (TDM) to improve IBD control, although controversies remain. The objective of this study was to evaluate the effectiveness of proactive TDM during induction and maintenance, based on the Bayesian approach, compared to standard management in IBD patients. Furthermore, the transition from reference IFX to the biosimilar CT-P13 is becoming more common in clinical practice, supported by multiple studies confirming its efficacy and safety. However, there are few cohort studies comparing the effectiveness, pharmacokinetic profiles, immunogenicity, and safety of reference IFX and CT-P13 in real-world clinical situations, which makes this study important. Objective The primary objective of the study was to evaluate clinical response during induction and maintenance, comparing differences based on the type of TDM (proactive or reactive) and the type of drug used (reference IFX or CT-P13). The secondary objective was to determine the number of patients achieving an optimal drug level (ITL) during induction and maintenance. Lastly, the drug survival (time from initiation to withdrawal) based on the type of TDM (proactive or reactive) and the type of drug (reference IFX or CT-P13) was evaluated. Patients and Methods Retrospective observational cohort of IBD patients aged >18 years, totaling 153 patients. They were initially classified into two groups based on the strategy used to optimize IFX dosage: a standard therapy group (ST group) with dose adjustment based on clinical factors and a therapeutic drug monitoring group (TDM group) with pharmacokinetic parameter estimation using Bayesian estimation. Additionally, this retrospective cohort was later classified into two groups based on the drug used (reference IFX or CT-P13). Results A total of 153 patients were included. The proportion of patients achieving primary response during induction was 51.8%, with a higher proportion in the TDM group (74.3% vs. 44.2%, p = 0.002). Regarding the variable "poor clinical outcomes" during induction, the proportion was lower in the TDM group (3.3% TDM vs. 21.1% ST, p = 0.024). The proportion of patients achieving secondary response was higher in the TDM group than in the ST group (80.7% vs. 61.4%, respectively, p = 0.023). The composite variable during maintenance was lower in the TDM group compared to the ST group (12.3% vs. 36.8%, respectively, p = 0.002). Comparing the type of drug used (reference IFX vs. CT-P13), the proportion of patients achieving clinical remission during induction and maintenance was 66.7% and 64%, respectively. No significant differences were observed between CT-P13 and reference IFX (74.4% vs. 62.3%, respectively, p = 0.178). In the TDM group, 40% of patients achieved an optimal ITL during induction, and 80% during maintenance. Differences in elimination half-life were found between patients with severe and mild-moderate disease during induction (6.1 days [IQR: 1.7] vs. 7.7 days [IQR: 3.0], p = 0.003), and between Crohn's disease and ulcerative colitis (7.8 days [IQR: 2.9] vs. 6.2 days [IQR: 1.7], p = 0.009). A correlation was also found between IFX elimination half-life and albumin concentration (Spearman's Rho = 0.344, p = 0.032). The median follow-up time was 39 weeks, and no differences were found between the TDM and ST groups (40.6 weeks vs. 38.7 weeks, p = 0.589). Treatment withdrawal occurred in 39 (25.5%) patients, with no differences between the two groups (24.0% vs. 26.9%, respectively, p = 0.678). No significant differences were observed between CT-P13 and reference IFX, and the only variable associated with better clinical control was dose adjustment through TDM. Conclusions Proactive TDM using the Bayesian approach is associated with higher response rates and fewer complications during both induction and maintenance phases. The efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity of CT-P13 in a real-world clinical setting are comparable to those of reference IFX.