Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, 0319, Oslo, Norway.
Department of Gastroenterology, Akershus University Hospital, Sykehusveien 75, 1478, Lørenskog, Norway.
Trials. 2020 Jan 6;21(1):13. doi: 10.1186/s13063-019-3734-4.
Infliximab (INX) and other tumour necrosis factor inhibitors (TNFi) have revolutionised the treatment of several immune mediated inflammatory diseases. Still, many patients do not respond sufficiently to therapy or lose efficacy over time. The large interindividual variation in serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be major reasons for treatment failures. Therapeutic drug monitoring (TDM), an individualised treatment strategy based on systematic assessments of serum drug concentrations, has been proposed as a clinical tool to optimise efficacy of INX treatment. TDM seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy has not yet been demonstrated in randomised clinical trials. The NORwegian DRUg Monitoring study (NOR-DRUM) aims to assess the effectiveness of TDM, both with regard to the achievement of remission in patients starting INX treatment (part A) as well as to maintain disease control in patients on INX treatment (part B).
The NOR-DRUM study is a randomised, open, controlled, parallel-group, comparative, multi-centre, national, superiority, phase IV study with two separate parts, NOR-DRUM A and NOR-DRUM B. Patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn's disease and psoriasis are included. In both study parts participants are randomised 1:1 to either TDM of infliximab (intervention group) or to standard treatment with infliximab without knowledge of drug levels or ADAb status (control group). NOR-DRUM A will include 400 patients starting INX therapy. The primary outcome is remission at 30 weeks. In NOR-DRUM B, 450 patients on maintenance treatment with INX will be included. The primary endpoint is occurrence of disease worsening during the 52-week study period.
As the first trial to assess the effectiveness, safety and cost-effectiveness of TDM in patients receiving TNFi for a range of immune mediated inflammatory diseases, we hope that the NOR-DRUM study will contribute to the advancement of evidence based personalised treatment with biological medicines.
Clinicaltrials.gov, NCT03074656. Registered on 090317.
英夫利昔单抗（INX）和其他肿瘤坏死因子抑制剂（TNFi）彻底改变了几种免疫介导的炎症性疾病的治疗方法。尽管如此，仍有许多患者对治疗反应不足或随着时间的推移疗效丧失。在标准剂量下，血清药物浓度存在较大的个体间差异，以及抗药物抗体的产生，被认为是治疗失败的主要原因。治疗药物监测（TDM）是一种基于对血清药物浓度进行系统评估的个体化治疗策略，被提议作为优化 INX 治疗效果的临床工具。从临床和经济角度来看，TDM 似乎都是合理的，但这种治疗策略的有效性尚未在随机临床试验中得到证实。挪威药物监测研究（NOR-DRUM）旨在评估 TDM 的有效性，既包括 INX 治疗起始患者达到缓解的情况（A 部分），也包括 INX 治疗患者维持疾病控制的情况（B 部分）。
NOR-DRUM 研究是一项随机、开放、对照、平行组、比较、多中心、全国性、优效性、四期研究，分为两个独立部分，即 NOR-DRUM A 和 NOR-DRUM B。纳入类风湿关节炎、银屑病关节炎、强直性脊柱炎、溃疡性结肠炎、克罗恩病和银屑病患者。在两个研究部分中，参与者均按 1:1 随机分配至英夫利昔单抗 TDM（干预组）或英夫利昔单抗标准治疗（对照组），且两组均不了解药物水平或 ADAb 状态。NOR-DRUM A 将纳入 400 例开始 INX 治疗的患者。主要结局为 30 周时的缓解。在 NOR-DRUM B 中，将纳入 450 例接受 INX 维持治疗的患者。主要终点为 52 周研究期间疾病恶化的发生。
作为评估 TDM 在接受 TNFi 治疗的一系列免疫介导的炎症性疾病患者中的有效性、安全性和成本效益的第一项试验，我们希望 NOR-DRUM 研究将有助于推进基于生物药物的个体化治疗的循证证据。
Clinicaltrials.gov，NCT03074656。于 2017 年 3 月 9 日注册。
