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

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.

Acknowledgements

We are grateful to all the rheumatologists and nurses of the Daycare Department for Biologics, and to the laboratory technicians of the Immunological Unit and the Spanish Society of Rheumatology, who assisted with the English-language correction of the manuscript.

No funding was received to perform this research.

Disclosure statement

CP-R has received research grants/honoraria from AbbVie, Lilly, Novartis, Pfizer, Sanofi, Biogen, and UCB. VN-C has received research grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer, and UCB; DP-S has received speaking fees from AbbVie, Pfizer, Takeda, Menarini, and Grifols. IM has received speaking fees from Roche. AB has received grant/research support and fees for consultancies or as a speaker from AbbVie, Amgen, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB, and Roche. No potential conflict of interest was reported by the remaining authors.