Ward M G, Thwaites P A, Beswick L, Hogg J, Rosella G, Van Langenberg D, Reynolds J, Gibson P R, Sparrow M P
Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.
Department of Gastroenterology, Eastern Health, Melbourne, Vic., Australia.
Aliment Pharmacol Ther. 2017 Apr;45(8):1135-1145. doi: 10.1111/apt.13992. Epub 2017 Feb 27.
Whether therapeutic drug monitoring for adalimumab needs to be performed at trough has not been defined.
To determine intra-patient adalimumab drug-level variation and to identify modulating patient and disease factors.
In this prospective observational study, adult patients with Crohn's disease established on maintenance adalimumab had drug levels measured repeatedly according to pre-defined schedules (visit 1: day 4-6, visit 2: day 7-9, trough: day 13-14) across two consecutive fortnightly cycles. Disease activity was assessed using Harvey-Bradshaw Index, C-reactive protein and faecal calprotectin. For this analysis, trough levels ≥4.9 μg/mL were considered therapeutic.
Nineteen patients underwent 111 evaluations. Mean intra-patient drug levels from paired visits between cycles did not differ (visit1 cycle1: 4.81, cycle2: 5.21 μg/mL, P = 0.24, visit2 cycle1: 4.86, cycle2: 4.82, P = 0.91 and trough cycle1: 3.95, cycle2: 3.95, P = 0.99), irrespective of disease activity. Drug levels were stable over the first 9 days (visit 1-2), but declined to trough by a mean 1.06 and 0.89 μg/mL between visit 1 or 2, respectively (P < 0.001). Models using nontemporal factors (smoking, syringe delivery device) and levels at earlier visits accounted for 66-80% of the variance in trough levels. On receiver-operating curve analysis, thresholds identified in the first 9 days that predicted a therapeutic trough level were similar to the trough threshold itself, with high sensitivity but modest specificity.
While therapeutic drug monitoring should be performed at trough, a drug level ≥4.9 μg/mL obtained during the first 9 days predicts a therapeutic trough drug level with reasonable confidence.
对于阿达木单抗是否需要在谷浓度时进行治疗药物监测尚未明确。
确定患者体内阿达木单抗药物水平的变化，并识别调节患者和疾病的因素。
在这项前瞻性观察研究中，已确定接受阿达木单抗维持治疗的成年克罗恩病患者按照预先定义的时间表（访视1：第4 - 6天，访视2：第7 - 9天，谷浓度：第13 - 14天）在两个连续的两周周期内多次测量药物水平。使用哈维 - 布拉德肖指数、C反应蛋白和粪便钙卫蛋白评估疾病活动度。对于该分析，谷浓度水平≥4.9μg/mL被视为治疗有效。
19名患者接受了111次评估。两个周期之间配对访视的患者体内平均药物水平无差异（访视1周期1：4.81，周期2：5.21μg/mL，P = 0.24；访视2周期1：4.86，周期2：4.82，P = 0.91；谷浓度周期1：3.95，周期2：3.95，P = 0.99），与疾病活动度无关。药物水平在最初9天（访视1 - 2）内稳定，但在访视1或访视2之间分别平均下降1.06和0.89μg/mL至谷浓度（P < 0.001）。使用非时间因素（吸烟、注射器给药装置）和早期访视时的水平建立的模型可解释谷浓度水平66 - 80%的变异。在接受者操作曲线分析中，在最初9天确定的预测治疗性谷浓度水平的阈值与谷浓度阈值本身相似，敏感性高但特异性一般。
虽然治疗药物监测应在谷浓度时进行，但在最初9天内获得的药物水平≥4.9μg/mL可较为可靠地预测治疗性谷浓度药物水平。
