Zeraatkar Dena, Pitre Tyler Stacy, Kirsh Sarah, Jassal Tanvir, Ling Michael, Hussain Muizz, Couban Rachel J, Kawano-Dourado Leticia, Kristianslund Eirik K, Olav Vandvik Per
Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
BMJ Med. 2024 Oct 28;3(1):e000998. doi: 10.1136/bmjmed-2024-000998. eCollection 2024.
To address the efficacy and safety of proactive therapeutic drug monitoring of biologic drugs for patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis.
Systematic review and meta-analysis.
Medline, Embase, Central, and CINAHL, from database inception to 23 May 2024.
Trials including people with inflammatory bowel disease, inflammatory arthritis, and psoriasis were selected. Selected trials also randomly assigned people to either proactive therapeutic drug monitoring of tumour necrosis factor-alpha inhibitors or other biologic drugs in the intervention group, and to either no therapeutic drug monitoring or standard care in the control group. Reviewers worked independently and in duplicate to screen search records and collect data from eligible trials. For each outcome, a frequentist, pairwise, random effects meta-analysis was done and the certainty of evidence was assessed using GRADE (grading of recommendations, assessment, development, and evaluations).
Of 10 eligible trials identified, reporting on 2383 patients, two investigated induction with infliximab (533 patients), four assessed maintenance with infliximab (901 patients), and three assessed maintenance with adalimumab (710 patients). One trial was of maintenance with infliximab, adalimumab, and etanercept (239 patients). For patients who had induction with infliximab, the effects of proactive therapeutic drug monitoring on remission and adverse events were uncertain. Low certainty evidence suggested that proactive therapeutic drug monitoring may have little or no effect on disease activity, physical function, mental health, and quality of life. For patients who had maintenance with infliximab, low certainty evidence suggested that proactive therapeutic drug monitoring may increase the proportion of patients who had sustained disease control or remission (relative risk 1.26 (95% confidence interval (CI) 1.14 to 1.40), absolute risk difference of 146 more per 1000 patients treated for one year (95% CI 78 to 224). Additionally, this treatment and monitoring may reduce disease worsening, and may have little or no effect on disease activity, physical function, mental health, and quality of life. The effects of proactive therapeutic drug monitoring of infliximab on adverse events and formation of anti-drug antibodies were uncertain. For patients who had maintenance with adalimumab, the effects of proactive therapeutic drug monitoring were uncertain.
Proactive therapeutic drug monitoring of infliximab during maintenance may help patients to have sustained disease control or remission. No compelling evidence supported the effectiveness of proactive therapeutic drug monitoring of infliximab during induction or proactive therapeutic drug monitoring of adalimumab during maintenance.
探讨对炎症性肠病、炎症性关节炎和银屑病患者进行生物药物主动治疗药物监测的疗效和安全性。
系统评价和荟萃分析。
Medline、Embase、Central和CINAHL，从数据库建立至2024年5月23日。
选择纳入炎症性肠病、炎症性关节炎和银屑病患者的试验。入选试验还将患者随机分为干预组，接受肿瘤坏死因子-α抑制剂或其他生物药物的主动治疗药物监测，对照组接受无治疗药物监测或标准治疗。评审员独立且重复地筛选检索记录，并从符合条件的试验中收集数据。对于每个结局，进行了频率学派、成对、随机效应荟萃分析，并使用GRADE（推荐分级、评估、制定和评价）评估证据的确定性。
在确定的10项符合条件的试验中，共报告了2383例患者，其中两项研究英夫利昔单抗诱导治疗（533例患者），四项评估英夫利昔单抗维持治疗（901例患者），三项评估阿达木单抗维持治疗（710例患者）。一项试验为英夫利昔单抗、阿达木单抗和依那西普的维持治疗（239例患者）。对于接受英夫利昔单抗诱导治疗的患者，主动治疗药物监测对缓解和不良事件的影响尚不确定。低确定性证据表明，主动治疗药物监测对疾病活动、身体功能、心理健康和生活质量可能几乎没有影响。对于接受英夫利昔单抗维持治疗的患者，低确定性证据表明，主动治疗药物监测可能会增加疾病持续得到控制或缓解的患者比例（相对风险1.26（95%置信区间（CI）1.14至1.40），每1000例接受治疗一年的患者中，绝对风险差异多146例（95%CI 78至224）。此外，这种治疗和监测可能会减少疾病恶化，对疾病活动、身体功能、心理健康和生活质量可能几乎没有影响。英夫利昔单抗主动治疗药物监测对不良事件和抗药物抗体形成的影响尚不确定。对于接受阿达木单抗维持治疗的患者，主动治疗药物监测的效果尚不确定。
英夫利昔单抗维持治疗期间的主动治疗药物监测可能有助于患者持续控制疾病或实现缓解。没有令人信服的证据支持英夫利昔单抗诱导治疗期间主动治疗药物监测的有效性，或阿达木单抗维持治疗期间主动治疗药物监测的有效性。
