title: Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis.
abstract: OBJECTIVE
  Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA.
  
  
  METHODS
  A total of 268 patients with active RA (disease activity score in 28 joints, DAS28>3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10mg/week plus LEF 20mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed.
  
  
  RESULTS
  The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P=0.013). The proportion of patients with ALT/AST >3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P=0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant (P>0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea.
  
  
  CONCLUSIONS
  Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX+LEF in the treatment of active RA patients.
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors: Nan
authors: N
authors: Xiang
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors: Xiao-Mei
authors: XM
authors: Li
authors: Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Miao-Jia
authors: MJ
authors: Zhang
authors: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Dong-Bao
authors: DB
authors: Zhao
authors: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Ping
authors: P
authors: Zhu
authors: Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
authors: Xiao-Xia
authors: XX
authors: Zuo
authors: Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Min
authors: M
authors: Yang
authors: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors: Yin
authors: Y
authors: Su
authors: Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors: Zhan-Guo
authors: ZG
authors: Li
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
authors: Zhu
authors: Z
authors: Chen
authors: Department of Rheumatology and Immunology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China. Electronic address: lixiangpei55@126.com.
authors: Xiang-Pei
authors: XP
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D008875:Middle Aged; D029596:Paeonia / Q000737:chemistry*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D005960:Glucosides; D007555:Isoxazoles; D000077339:Leflunomide; D008727:Methotrexate
keywords: Hepatic dysfunction; Rheumatoid arthritis; Total glucosides of paeony