Background/Purpose: Infliximab (Ifx) has proven to be efficacious for improving symptoms in patients with axial SpA(axSpA).  Several factors may influence the pharmacokinetic-pharmacodynamic of Ifx and its relation with clinical response such as: disease activity, anti-drug antibodies and the use of concomitant conventional synthetic DMARDs. The prediction of early response through Ifx concentrations could be a feasible tool to optimize the early detection of non-responders to Ifx therapy.

The main objective is to identify if serum Ifx trough levels at early stages of treatment could predict the non-response in patients with axSpA. The secondary objective was to analyze if early drug levels could also predict the development of secondary inefficacy.

Methods: Observational study including 75 patients with axSpA recruited from the axSpA-Paz cohort treated with Ifx and monitored during 52 weeks (W).. Serum Ifx levels and ADA were measured by capture and bridging ELISA respectively at baseline, W2, W6, W12 and W24. Disease activity was assessed at baseline, W24 and W52 by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical response was defined by ΔASDAS≥1.1. The association between serum Ifx trough levels at early stages and clinical response at W52 was evaluated. After that, receiver operating characteristic (ROC) curves for the outcome of clinical response after 52W of treatment were employed to determine the best cut-off values for serum Ifx trough levels. The association between the best cut-off Ifx levels at early stages and clinical outcomes was evaluated by a logistic regression analysis. Ifx survival was evaluated through Kaplan-Meier curves.

Results: Out of the 75 patients studied, 37(49%) were non-responders and 38 (51%) were responders. During the treatment with Ifx, 35(47%) patients discontinued Ifx, most of them due to secondary inefficacy 27/35(77%). Patients with good response after 52W tended to have higher Ifx concentrations compared with non- responder patients at W12: 6.9(4.7-10.7) vs 3.1(0.7-8.5); p=0.006. In addition, patients with concomitant MTX had higher serum Ifx trough levels (median and IQR) than patients without MTX at different time points: at W6: 25.9(16-40) vs 16(11.3-26.6); p=0.008; at W12: 8.6(5.2-12) vs 3.8(1.7-7.7); p=0.005 and at W22: 4.7(2.1-8.3) vs 3.1(0.6-5.1); p=0.007; respectively). ROC curve for serum Ifx concentrations at W12 showed an area under the curve of 0.687 (95% confidence interval (CI): 0.558-0.815), p< 0.01). A cut-off of 6.7 µg/mL showed a sensitivity of 52% and specificity of 71%.Values < 6.7 µg/mL were found to be associated with lower ΔASDAS at W52 (OR: 2.7; 95%CI: 1.0-7.1). The regression analysis showed that Ifx concentrations < 6.7 µg/mL at W12 also predict the dropout due to secondary inefficacy (OR: 3.5; 95%CI: 1.2-10.2).  The mean survival time was significantly shorter in patients with Ifx levels at W12 < 6.7 µg/mL compared with patients with levels above this cut-off: 5.3 years (95% CI: 4.1-6.5) vs 8 years (95% CI: 6.4-9.7);p=0.03.

Conclusion: Serum Ifx trough levels at W12< 6.7 µg/mL are associated with non-clinical response during the first year of Ifx therapy, more risk to develop secondary inefficacy and a shorter drug survival in patients with axSpA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/infliximab-serum-trough-levels-predict-non-clinical-response-in-patients-with-axial-spondyloarthritis/