Early monitoring of infliximab serum trough levels predicts long-term therapy failure in patients with axial spondyloarthritis

A Martínez-Feito,V Navarro-Compán,B Hernández-Breijo,E Olariaga-Mérida,D Peiteado,A Villalba,L Nuño,I Monjo,C Diego,D Pascual-Salcedo,P Nozal,A Balsa,C Plasencia-Rodríguez

doi:10.1080/03009742.2021.1914430

Abstract

Objective To evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA). Methods Longitudinal observational study involving 81 patients with axSpA monitored during infliximab therapy. Serum ITL were measured before starting infliximab treatment and at weeks 2 (W2), W6 and W12 of treatment. Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline, W24 and W52, and every 6 months thereafter until treatment discontinuation, regardless of the reason. Non-clinically important improvement was defined by ΔASDAS<1.1. The association between serum levels during the early stages and clinical outcomes (non-clinically important improvement at W52, drug survival and drop-out due to secondary inefficacy) was investigated through logistic regression models and Kaplan Meier curves. Receiver operating characteristic (ROC) curves were employed to determine the best cut-off for serum ITL. Results Out of the 81 patients, 45 (56%) did not achieve clinical improvement at W52. These patients had lower serum ITL at W12 compared to those who improved: ITL [median (IQR)]: 4.1(0.9-8.3) µg/mL vs 7.1 (4.3–11.3) µg/mL, respectively;p = 0.007). ITL<6.7 µg/mL at W12 was significantly associated with: i) not achieving clinical improvement at W52 (OR: 2.3; 95%CI: 1.3–3.9); ii) shorter drug survival (5.0 years (95% CI 3.8–6.2) vs 7.0 years (95% CI 4.8–6.9; p = 0.04), and iii) higher drop-out rates due to secondary inefficacy (OR: 3.5; 95% CI: 1.2–10.2). Conclusion Low serum ITL at W12 were associated with long-term clinical failure in patients with axSpA, due to secondary inefficacy.

Highlights

In axial spondyloarthritis, tumor necrosis inhibitors (TNFi) have been shown to be effective for improving signs and symptoms in cases of persistently high disease activity [1]
In this study we have shown an association between serum infliximab trough levels (ITL) during early stages of the treatment and long-term clinical failure to Ifx, based on non- clinically important improvement at week 52, drug survival and drop-out due to secondary inefficacy in patients with axial spondyloarthritis (axSpA)
We defined an ITL cut-off at W12 as predictive of long-term clinical failure in patients with axSpA treated with Ifx

Summary

Introduction

In axial spondyloarthritis (axSpA), tumor necrosis inhibitors (TNFi) have been shown to be effective for improving signs and symptoms in cases of persistently high disease activity [1]. TNFi are recommended as the first biological therapy for patients with axSpA In such cases, infliximab (Ifx), a chimeric TNFi, is widely used in clinical practice. Data from clinical registries have shown that after 2 years of treatment up to 30–45% of patients experience therapy interruption, clinical inefficacy being the main reason for discontinuation [2, 3]. Out of these patients, 19–23% experience lack of efficacy from the very beginning of treatment, while the rest initially respond to infliximab but somehow lose this response over time. The aim of our study is to evaluate whether serum infliximab trough levels (ITL) during the early stages of treatment are predictive of long-term clinical failure in patients with axial spondyloarthritis (axSpA)

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