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.

中文翻译：

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英夫利昔单抗血清谷浓度的早期监测可预测中轴型脊柱关节炎患者的长期治疗失败

客观的

评估治疗早期阶段的血清英夫利昔单抗谷浓度 (ITL) 是否可预测中轴型脊柱关节炎 (axSpA) 患者的长期临床失败。

方法

在英夫利昔单抗治疗期间监测了 81 名 axSpA 患者的纵向观察性研究。在开始英夫利昔单抗治疗之前和治疗的第 2 周 (W2)、W6 和 W12 测量血清 ITL。在基线、第 24 周和第 52 周以及此后每 6 个月通过强直性脊柱炎疾病活动评分 (ASDAS) 评估疾病活动性，直到治疗中止，无论原因如何。ΔASDAS<1.1 定义了非临床重要的改善。通过逻辑回归模型和 Kaplan Meier 曲线研究了早期阶段血清水平与临床结果（第 52 周的非临床重要改善、药物存活和继发性无效导致的退出）之间的关联。受试者工作特征 (ROC) 曲线用于确定血清 ITL 的最佳截止值。

结果

在 81 名患者中，45 名（56%）在第 52 周时未达到临床改善。与改善的患者相比，这些患者在第 12 周的血清 ITL 较低：ITL [中位数 (IQR)]：分别为 4.1(0.9-8.3) µg/mL 和 7.1 (4.3–11.3) µg/mL；p = 0.007)。第 12 周 ITL<6.7 µg/mL 与以下因素显着相关：i) 第 52 周未实现临床改善（OR：2.3；95%CI：1.3–3.9）；ii) 较短的药物生存期（5.0 年 (95% CI 3.8-6.2) 与 7.0 年（95% CI 4.8-6.9；p = 0.04），以及 iii) 由于继发性无效导致的较高退出率（OR：3.5；95 % CI：1.2–10.2)。

结论

由于继发性无效，第 12 周的低血清 ITL 与 axSpA 患者的长期临床失败有关。