Du Fang, Dai Qing, Teng Jialin, Lu Liangjing, Ye Shuang, Ye Ping, Lin Zhiqian, Ding Hong, Dai Min, Bao Chunde
Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200001, China.
Department of Radiology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200001, China.
Chin Med J (Engl). 2024 Jul 26. doi: 10.1097/CM9.0000000000003200.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX.
This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52.
The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 (P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant.
IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA.
https://classic.clinicaltrials.gov/, NCT01548001.
类风湿关节炎（RA）是一种以慢性炎症和关节破坏为特征的全身性自身免疫性疾病。艾拉莫德（IGU）是一种新型的传统合成改善病情抗风湿药（csDMARD），在中国和日本治疗活动性RA具有良好的疗效和安全性。然而，IGU对活动性RA患者骨破坏进展或影像学进展的长期影响尚不清楚。我们旨在研究艾拉莫德（IGU）、甲氨蝶呤（MTX）与IGU联合用药以及IGU在初治MTX的活动性类风湿关节炎（RA）患者中的疗效和安全性。
这项多中心、双盲、随机、非劣效性临床试验在中国28个中心进行，为期52周以上。总共911例患者被随机分为三组（1:1:1），分别接受MTX单药治疗（每周10 - 15mg，n = 293）、IGU单药治疗（每日2次，每次25mg，n = 297）或IGU + MTX（MTX每周10 - 15mg，IGU每日2次，每次25mg，n = 305），疗程为52周。在基线时评估患者的临床特征、简化疾病活动指数（SDAI）、临床疾病活动指数（CDAI）、28个关节疾病活动评分 - C反应蛋白（DAS28 - CRP）水平和红细胞沉降率（DAS28 - ESR）。主要终点是根据美国风湿病学会（ACR20）反应改善≥20%的患者比例以及第52周时范德海伊德改良总夏普评分（vdH - mTSS）的变化。
在第52周时，IGU单药治疗、IGU + MTX和MTX单药治疗达到ACR20反应的患者比例分别为77.44%、77.05%和65.87%。IGU单药治疗相对于MTX单药治疗的非劣效性在ACR20（11.57%；95%置信区间[CI]，4.35 - 18.79%；P <0.001）和vdH - mTSS（ - 0.37；95% CI， - 1.22 - 0.47；P = 0.022）方面得到确立。IGU单药治疗在ACR20方面也优于MTX单药治疗（P = 0.002），但在vdH - mTSS方面并非如此。IGU + MTX相对于MTX单药治疗在ACR20方面的优越性得到证实（11.18%；95% CI，3.99 - 18.37%；P = 0.003），但在vdH - mTSS方面未得到证实（ - 0.68；95% CI， - 1.46 - 0.11；P = 0.091）。然而，不良事件发生率的差异无统计学意义。
IGU单药治疗/IGU + MTX比MTX单药治疗显示出更有利的临床反应。在影像学进展方面，IGU可能比MTX具有一些临床益处，这意味着IGU可被视为活动性RA患者的初始治疗选择。
