Clinical Pharmacology Unit, Zealand University Hospital, Roskilde, Denmark.
Department of Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
JAMA Netw Open. 2023 Oct 2;6(10):e2335950. doi: 10.1001/jamanetworkopen.2023.35950.
This is the first network meta-analysis to assess outcomes associated with multiple conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid.
To analyze clinical outcomes after treatment with conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid among patients with rheumatoid arthritis.
With no time restraint, English language articles were searched in MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, and reference lists of relevant meta-analyses until September 15, 2022.
Four reviewers in pairs of 2 independently included controlled studies randomizing patients with rheumatoid arthritis to mono-conventional synthetic disease-modifying antirheumatic drugs, glucocorticoid, placebo, or nonactive treatment that recorded at least 1 outcome of tender joint count, swollen joint count, erythrocyte sedimentation rate, and C-reactive protein level. Of 1098 assessed articles, 130 articles (132 interventions) were included.
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, and data quality was assessed by the Cochrane risk of bias tool RoB 2. Data were extracted by a single author and checked independently by 2 authors. Data were analyzed using a random effect model, and data analysis was conducted from June 2021 to February 2023.
A protocol with hypothesis and study plan was registered before data recording. The most complete of recorded outcomes (tender joint count) was used as primary outcome, with imputations based on other outcomes to obtain a full analysis of all studies. Absolute change adjusted for baseline disease activity was assessed.
A total of 29 interventions in 275 treatment groups among 132 randomized clinical trials (mean [range], 71.0% [27.0% to 100%] females in studies; mean [range] of ages in studies, 53 [36 to 70] years) were identified, which included 13 260 patients with rheumatoid arthritis. The mean (range) duration of RA was 79 (2 to 243) months, and the mean (range) disease activity score was 6.3 (4.0 to 8.8). Compared with placebo, oral methotrexate was associated with a reduced tender joint count by 5.18 joints (95% credible interval [CrI], 4.07 to 6.28 joints). Compared with methotrexate, glucocorticoid (-2.54 joints; 95% CrI, -5.16 to 0.08 joints) and remaining drugs except cyclophosphamide (6.08 joints; 95% CrI, 0.44 to 11.66 joints) were associated with similar or lower tender joint counts.
This study's results support the present role of methotrexate as the primary reference conventional synthetic disease-modifying antirheumatic drug.
这是第一项评估多种常规合成疾病修饰抗风湿药物和糖皮质激素相关结局的网络荟萃分析。
分析类风湿关节炎患者使用常规合成疾病修饰抗风湿药物和糖皮质激素后的临床结局。
无时间限制,在 MEDLINE、Embase、Cochrane 中心、ClinicalTrials.gov 和相关荟萃分析的参考文献列表中搜索英文文献,直到 2022 年 9 月 15 日。
4 位审稿人两两一组独立纳入将类风湿关节炎患者随机分配至单种常规合成疾病修饰抗风湿药物、糖皮质激素、安慰剂或非活性治疗的对照研究,这些研究记录了至少 1 项结局,包括压痛关节计数、肿胀关节计数、红细胞沉降率和 C 反应蛋白水平。在评估的 1098 篇文章中,有 130 篇文章(132 项干预措施)入选。
该综述遵循系统评价和荟萃分析的 Preferred Reporting Items 报告指南,并使用 Cochrane 偏倚风险工具 RoB 2 评估数据质量。由一位作者独立提取数据,并由两位作者独立检查。使用随机效应模型进行数据分析,数据分析时间为 2021 年 6 月至 2023 年 2 月。
在记录数据之前,制定了假设和研究计划的方案。使用记录的最完整结局(压痛关节计数)作为主要结局,并基于其他结局进行推断,以对所有研究进行全面分析。评估了调整基线疾病活动度后的绝对变化。
共确定了 275 个治疗组中的 29 项干预措施(研究中女性比例[范围]为 71.0%[27.0%至 100%];研究中平均[范围]年龄为 53[36 至 70]岁),共纳入 1320 例类风湿关节炎患者。类风湿关节炎的平均(范围)病程为 79(2 至 243)个月,平均(范围)疾病活动评分(DAS)为 6.3(4.0 至 8.8)。与安慰剂相比,口服甲氨蝶呤可使压痛关节计数减少 5.18 个关节(95%可信区间[CrI],4.07 至 6.28 个关节)。与甲氨蝶呤相比,糖皮质激素(-2.54 个关节;95% CrI,-5.16 至 0.08 个关节)和除环磷酰胺以外的其他药物(6.08 个关节;95% CrI,0.44 至 11.66 个关节)与相似或更低的压痛关节计数相关。
本研究结果支持甲氨蝶呤作为主要参考常规合成疾病修饰抗风湿药物的现有作用。