Almoallim Hani M, Omair Mohammed A, Ahmed Sameh A, Vidyasagar Kota, Sawaf Bisher, Yassin Mohamed A
Department of Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah 24382, Saudi Arabia.
Rheumatology Unit, Department of Medicine, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Jan 28;18(2):178. doi: 10.3390/ph18020178.
BACKGROUND/OBJECTIVE: Janus Kinase inhibitors (JAKinibs) are effective and well-tolerated targeted therapies for rheumatoid arthritis (RA). The comparative efficacy and safety of different JAKinibs remains unclear. This network meta-analysis (NMA) aimed to assess the relative efficacy and safety of different available JAKinibs.
Searches were conducted on PubMed, CENTRAL, and ClinicalTrials.gov for randomized, double-blind, placebo-controlled trials comparing JAKinibs in RA patients. A frequentist NMA using the Netmeta package in R (R.4.3.0) was performed to evaluate both efficacy and safety outcomes. Continuous outcomes were presented as mean differences (MDs) and binary outcomes as relative risks (RR) with 95% confidence intervals (CI). The Cochrane risk of bias tool was used to assess the risk of bias in the included trials.
The analysis encompassed 39 trials with a total of 16,894 participants. Six JAKinibs (tofacitinib, baricitinib, upadacitinib, decernotinib, peficitinib, and filgotinib) were compared. Decernotinib at a dose of 300 mg showed a higher ACR50 response than other JAKinibs (RR = 7.55, 95% CI: 3.48 to 16.39, < 0.01, surface under the cumulative ranking curve (SUCRA): 0.92). Tofacitinib at a dose of 1 mg twice daily had a significantly lower incidence of adverse drug reactions (ADRs) compared to other JAKinibs (RR = 0.80, 95% CI: 0.65 to 0.99, = 0.04, SUCRA: 0.89), filgotinib 100 mg had a significantly lower infection risk (RR = 0.40, 95% CI: 0.21 to 0.79, < 0.01, SUCRA: 0.90), whereas baricitinib 4 mg had the significantly highest herpes zoster risk (RR = 4.79, 95% CI: 1.03 to 22.21, = 0.05, SUCRA: 0.11) compared to other JAKinibs.
This NMA's results indicate that commercially available JAKinibs show superior ACR responses and have comparable tolerability to placebo.
背景/目的：Janus激酶抑制剂（JAK抑制剂）是治疗类风湿性关节炎（RA）的有效且耐受性良好的靶向疗法。不同JAK抑制剂的相对疗效和安全性尚不清楚。本网络荟萃分析（NMA）旨在评估不同可用JAK抑制剂的相对疗效和安全性。
在PubMed、CENTRAL和ClinicalTrials.gov上进行检索，以查找比较JAK抑制剂治疗RA患者的随机、双盲、安慰剂对照试验。使用R（R.4.3.0）中的Netmeta软件包进行频率学派NMA，以评估疗效和安全性结果。连续结果以平均差（MDs）表示，二元结果以相对风险（RR）和95%置信区间（CI）表示。采用Cochrane偏倚风险工具评估纳入试验的偏倚风险。
该分析纳入了39项试验，共16,894名参与者。比较了六种JAK抑制剂（托法替布、巴瑞替尼、乌帕替尼、迪塞替尼、培非替尼和非戈替尼）。300 mg剂量的迪塞替尼显示出比其他JAK抑制剂更高的美国风湿病学会50%改善标准（ACR50）反应（RR = 7.55，95% CI：3.48至16.39，P < 0.01，累积排名曲线下面积（SUCRA）：0.92）。与其他JAK抑制剂相比，每日两次服用1 mg剂量的托法替布药物不良反应（ADR）发生率显著更低（RR = 0.80，95% CI：0.65至0.99，P = 0.04，SUCRA：0.89），100 mg剂量的非戈替尼感染风险显著更低（RR = 0.40，95% CI：0.21至0.79，P < 0.01，SUCRA：0.90），而与其他JAK抑制剂相比，4 mg剂量的巴瑞替尼带状疱疹风险显著最高（RR = 4.79，95% CI：1.03至22.21，P = 0.05，SUCRA：0.11）。
本NMA的结果表明，市售JAK抑制剂显示出优于安慰剂的ACR反应，且耐受性与安慰剂相当。
