抗英夫利昔单抗抗体浓度可指导临床缓解后复发的克罗恩病患者进行治疗强化。
Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response.
机构信息
Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Translational Research in GastroIntestinal Disorders (TARGID), Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
出版信息
Aliment Pharmacol Ther. 2018 Feb;47(3):346-355. doi: 10.1111/apt.14452. Epub 2017 Dec 11.
BACKGROUND
The presence of antibodies towards infliximab (ATI) is associated with lower infliximab (IFX) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease (CD).
AIM
To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX.
METHODS
A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification.
RESULTS
Clinical response (physicians' global assessment) and biological response and remission (CRP) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 μg/mL [0.3-3.6] at T0 to 3.6 μg/mL [0.5-10.2] at T+1 (P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r -0.57, P < .0001) and the probability of clinical response (P = 0.034) at T+1. When ATI were quantifiable but <282 ng/mL eq. at T0, combined interval shortening and dose doubling was more effective for restoring therapeutic IFX trough concentrations (≥3 μg/mL at T+1) than dose doubling alone, which in turn was more effective than interval shortening alone (P < .001).
CONCLUSION
Antibodies towards infliximab can guide clinical decision-making on treatment intensification.
背景
针对英夫利昔单抗（ATI）的抗体的存在与较低的英夫利昔单抗（IFX）谷浓度和应答丧失有关。在大多数但不是所有克罗恩病（CD）患者中，IFX 治疗强化对于恢复应答是有效的。
目的
比较 CD 患者在 IFX 维持治疗中失去临床应答后，强化治疗策略的结果、药代动力学和免疫原性。
方法
进行了一项回顾性队列研究，纳入了 103 例在 IFX 维持治疗中失去临床应答的 CD 患者，这些患者接受了双倍剂量 IFX（10mg/kg）和/或缩短间隔后的下一次输注。在治疗强化前后（T0 和 T+1），连续的谷样品中测量 IFX 和 ATI 浓度。
结果
63%、42%和 24%的患者（在 T+1 评估时）恢复了临床应答（医生总体评估）和生物学应答和缓解（CRP）。治疗强化将 IFX 谷浓度从 T0 时的 1.2μg/mL[0.3-3.6]提高到 T+1 时的 3.6μg/mL[0.5-10.2]（P<0.0001）。使用药物耐受测定法，在 47%的患者的 T0 样本中检测到了 ATI。ATI 对达到的 IFX 谷浓度（Spearman r=-0.57，P<0.0001）和 T+1 时临床应答的概率（P=0.034）有负面影响。当 T0 时 ATI 可定量但<282ng/mL eq.时，与单独剂量加倍相比，联合缩短间隔和剂量加倍更有效地恢复治疗性 IFX 谷浓度（T+1 时≥3μg/mL），而单独缩短间隔更有效（P<0.001）。
结论
针对英夫利昔单抗的抗体可以指导强化治疗的临床决策。
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