Additive effect of leflunomide and glucocorticoids compared with glucocorticoids monotherapy in preventing relapse of IgG4-related disease: A randomized clinical trial

被引:25
作者
Wang, Yiwen [1 ]
Zhao, Zheng [1 ]
Gao, Dai [1 ]
Wang, Hui [1 ]
Liao, Simin [1 ]
Dong, Chongya [2 ]
Luo, Gui [1 ]
Ji, Xiaojian [1 ]
Li, Yan [1 ]
Wang, Xiuru [1 ]
Zhao, Yurong [1 ]
Li, Kunpeng [1 ]
Zhang, Jie [1 ]
Jin, Jingyu [1 ]
Zhang, Yamei [1 ]
Zhu, Jian [1 ]
Zhang, Jianglin [1 ]
Huang, Feng [1 ,3 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Rheumatol, 28 Fuxing Rd, Beijing 100853, Peoples R China
[2] Peking Univ First Hosp, Dept Biostat, 8 Xishiku St, Beijing 100034, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, State Key Lab Kidney Dis, 28 Fuxing Rd, Beijing 100853, Peoples R China
关键词
IgG4-related disease; Immunosuppressive agents; Leflunomide; Glucocorticoids; Randomized controlled trial; AUTOIMMUNE PANCREATITIS; TAKAYASU ARTERITIS; MAINTENANCE; AZATHIOPRINE; THERAPY; METHOTREXATE; COMBINATION; REMISSION; STATEMENT; ARTHRITIS;
D O I
10.1016/j.semarthrit.2020.01.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). Methods: A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5-0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. Results: Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13-0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01-3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of <= 5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). Conclusion: LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs mono therapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD. (C) 2020 Published by Elsevier Inc.
引用
收藏
页码:1513 / 1520
页数:8
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