Meziridis Giannis, Sidiropoulou Penelope, Pourzitaki Chrysa, Haidich Anna-Bettina, Tsaousi Georgia
Department of Trauma and Orthopaedics, General Hospital Wolfhagen, Wolfhagen, DEU.
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, GRC.
Cureus. 2024 Dec 27;16(12):e76466. doi: 10.7759/cureus.76466. eCollection 2024 Dec.
This study aims to assess the efficacy and safety of newly approved Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors in patients with moderately-to-severely active rheumatoid arthritis (RA) with inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs. We conducted a systematic review and meta-analysis of all placebo-controlled randomized trials assessing baricitinib, sarilumab, and upadacitinib treatment in RA, published in PubMed and CENTRAL (Cochrane Central Register of Controlled Trials) databases up to October 2023. The study outcomes involved the American College of Rheumatology (ACR) 20%, 50%, and 70% responses, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints (DAS28), serious adverse events, and adverse events leading to drug discontinuation. Twelve randomized controlled trials enrolling 5875 patients were selected for final analysis. Pooled analysis revealed that the implementation of baricitinib (RR = 1.77; 95% CI = 1.58-1.97; I = 21%), sarilumab (RR = 1.60; 95% CI = 1.33-1.93; I= 0%), and upadacitinib (RR = 1.99; 95% CI = 1.81-2.20; I = 15%) was associated with notable therapeutic improvement in RA patients as determined by the ACR20. Considering other efficacy outcomes (ACR50, ACR70, DAS28, HAQ-D), all tested interventions demonstrated a superiority to placebo. None of the tested treatment modalities incurred a higher risk of serious adverse events compared to placebo, yet drug discontinuation was more commonly encountered in baricitinib-treated patients. The newly approved JAK and IL-6 inhibitors, namely, baricitinib, upadacitinib, and sarilumab, seem to be effective in alleviating RA-induced clinical implications and thus improving quality of life. Nonetheless, safety issues could be a matter of concern in baricitinib use, while upadacitinib and sarilumab present an acceptable safety profile.
本研究旨在评估新批准的Janus激酶（JAK）抑制剂和白细胞介素-6（IL-6）抑制剂对传统抗风湿药物反应不足或不耐受的中度至重度活动性类风湿关节炎（RA）患者的疗效和安全性。我们对截至2023年10月发表在PubMed和CENTRAL（Cochrane对照试验中央注册库）数据库中评估巴瑞替尼、托珠单抗和乌帕替尼治疗RA的所有安慰剂对照随机试验进行了系统评价和荟萃分析。研究结局包括美国风湿病学会（ACR）20%、50%和70%反应率、健康评估问卷残疾指数（HAQ-DI）、28个关节疾病活动评分（DAS28）、严重不良事件以及导致停药的不良事件。最终分析选取了12项纳入5875例患者的随机对照试验。汇总分析显示，根据ACR20标准，使用巴瑞替尼（RR = 1.77；95%CI = 1.58 - 1.97；I² = 21%）、托珠单抗（RR = 1.60；95%CI = 1.33 - 1.93；I² = 0%）和乌帕替尼（RR = 1.99；95%CI = 1.81 - 2.20；I² = 15%）与RA患者显著的治疗改善相关。考虑其他疗效结局（ACR50、ACR70、DAS28、HAQ-D），所有受试干预措施均显示优于安慰剂。与安慰剂相比，受试治疗方式均未带来更高的严重不良事件风险，但巴瑞替尼治疗的患者更常出现停药情况。新批准的JAK和IL-6抑制剂，即巴瑞替尼、乌帕替尼和托珠单抗，似乎可有效缓解RA所致的临床症状，从而改善生活质量。尽管如此，巴瑞替尼的使用可能存在安全问题，而乌帕替尼和托珠单抗的安全性尚可接受。
