Department of Dermatology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Epidemiology and Data Science, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
J Eur Acad Dermatol Venereol. 2023 Sep;37(9):1815-1824. doi: 10.1111/jdv.19089. Epub 2023 Apr 17.
Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied.
To investigate the three-year follow-up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis.
We conducted a multicentre RCT in the Netherlands and Belgium. Randomization was performed by a centralized online randomization service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomized to. Patients becoming non-adherent to the biologic were excluded from analyses.
Sixty-one patients were included and 37 patients (ADL group n = 17, ADL + MTX group n = 20) continued in the follow-up study after 1 year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL + MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p = 0.326, week 145: 51.6% vs. 41.4%; p = 0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL + MTX group.
In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.
阿达木单抗（ADL）治疗的患者会产生抗药物抗体（ADA）。这可能会增加 ADL 的清除率，从而导致（继发性）无应答。ADL 与甲氨蝶呤（MTX）联合治疗可降低 ADA 水平，并在风湿性疾病中具有临床获益。然而，在银屑病中，尚未研究其长期有效性和安全性。
调查 ADL 联合 MTX 治疗初治中重度斑块型银屑病患者的三年随访数据，与 ADL 单药治疗相比。
我们在荷兰和比利时进行了一项多中心 RCT。通过中央在线随机服务进行随机分组。患者在第 145 周前每 12 周接受一次检查。评估人员设盲。我们收集了开始 ADL 联合 MTX 治疗与 ADL 单药治疗的患者的药物存活率、疗效、安全性、药代动力学和免疫原性数据。我们提供描述性分析，根据最初随机分组的组对患者进行分析。对不依从生物制剂的患者进行排除分析。
共纳入 61 例患者，其中 37 例（ADL 组 n=17，ADL+MTX 组 n=20）在 1 年后继续进行随访研究。在第 109 周和第 145 周时，ADL+MTX 组的药物存活率较 ADL 组有延长趋势（第 109 周：54.8%比 41.4%；p=0.326，第 145 周：51.6%比 41.4%；p=0.464）。在第 145 周，有 7/13 例患者接受 MTX 治疗。ADL 组中有 4/12 例完成研究的患者产生 ADA，而 ADL+MTX 组中有 3/13 例。
在这项小型研究中，与 ADL 单药治疗相比，ADL 联合 MTX 治疗的总体药物存活率没有显著差异。联合治疗组因不良事件停药的情况较为常见。为了确保可获得的医疗保健，可考虑在个别患者中联合使用 ADL 和 MTX 治疗。
