To identify a therapeutic target interval for certolizumab pegol drug levels and examine the influence of anti-drug antibodies in patients with inflammatory joint diseases. Certolizumab pegol and anti-drug antibody levels were measured in serum samples collected after 3 months of certolizumab pegol treatment in 268 patients with inflammatory joint diseases (116 axial spondyloarthritis, 91 rheumatoid arthritis and 61 psoriatic arthritis) in the NOR-DMARD study. Treatment response was defined by Ankylosing Spondylitis Disease Activity Score Clinically important improvement in axial spondyloarthritis, European League Against Rheumatism good/moderate response in rheumatoid arthritis, and improvement in 28-joint Disease Activity Score of ≥ 0.6 in PsA. Serum drug levels and anti-drug antibodies were analysed using automated in-house assays. Certolizumab pegol serum levels varied considerably between individuals (median (IQR) 32.9 (17.3–43.9) mg/L). Certolizumab pegol level ≥ 20 mg/L was associated with treatment response for the total inflammatory joint disease population, with odds ratio (OR) 2.3 (95% CI 1.2–4.5, P = 0.01) and OR 1.9 (95% CI 1.0–3.5, P = 0.05) after 3 and 6 months of treatment, respectively. For individual diagnoses, this association was most consistent for axial spondyloarthritis, with OR 3.4 (95% CI 1.0–11.1, P < 0.05) and OR 3.3 (95% CI 1.0–10.8, P < 0.05), respectively. Certolizumab pegol level > 40 mg/L was not associated with any additional benefit for any of the diagnoses. Anti-drug antibodies were detected in 6.1% (19/310) of samples and were associated with low certolizumab pegol levels (P < 0.01). Serum certolizumab pegol levels 20–40 mg/L were associated with treatment response in inflammatory joint diseases. Our study is the first to show this association in axial spondyloarthritis and psoriatic arthritis patients. The results suggest a possible benefit of therapeutic drug monitoring in patients with inflammatory joint disease on certolizumab pegol treatment. NCT01581294, April 2012.

中文翻译：

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炎性关节疾病患者西妥珠单抗聚乙二醇乙二醇酯血清水平，抗药物抗体与治疗反应之间的关联：NOR-DMARD研究的数据。

为了确定certolizumab聚乙二醇药物水平的治疗目标间隔，并检查抗药物抗体对炎性关节疾病患者的影响。在NOR-DMARD研究中，对268例炎性关节疾病（116例轴向脊柱关节炎，91例类风湿关节炎和61例银屑病关节炎）患者接受certolizumab pegol治疗3个月后收集的血清样品中，测定了Certolizumab pegol和抗药物抗体的水平。强直性脊柱炎疾病活动度评分定义了治疗反应。临床上重要的改善是轴向性脊椎关节炎，欧洲风湿病联盟对类风湿关节炎的良好/中度反应以及PsA中28关节疾病活动度评分≥0.6的改善。使用自动内部分析法分析血清药物水平和抗药物抗体。个体之间的Certolizumab pegol血清水平差异很大（中位数（IQR）32.9（17.3–43.9）mg / L）。Certolizumab聚乙二醇水平≥20 mg / L与总炎症性关节疾病人群的治疗反应相关，优势比（OR）为2.3（95％CI 1.2-4.5，P = 0.01）和OR 1.9（95％CI 1.0-3.5） ，分别为3个月和6个月。对于个体诊断，这种关联在轴性脊椎关节炎中最为一致，分别为OR 3.4（95％CI 1.0-11.1，P <0.05）和OR 3.3（95％CI 1.0-10.8，P <0.05）。Certolizumab聚乙二醇水平> 40 mg / L与任何诊断的额外益处均无关联。在6.1％（19/310）的样品中检测到抗药物抗体，并与西妥珠单抗聚乙二醇化水平低相关（P <0.01）。血清西妥珠单抗聚乙二醇水平20–40 mg / L与炎症性关节疾病的治疗反应相关。我们的研究是第一个显示这种关联的轴向脊椎关节炎和银屑病关节炎患者。这些结果表明，对治疗性炎性关节疾病的患者进行西妥珠单抗聚乙二醇化治疗可能具有监测治疗药物的益处。NCT01581294，2012年4月。