PMID- 35991879
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220823
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Effectiveness and Safety of Iguratimod Monotherapy or Combined With Methotrexate 
      in Treating Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.
PG  - 911810
LID - 10.3389/fphar.2022.911810 [doi]
LID - 911810
AB  - Objectives: We aimed to estimate the effectiveness and safety of iguratimod (IGU) 
      monotherapy or in combination with methotrexate (MTX) in treating rheumatoid 
      arthritis (RA) to provide an evidence-primarily-based foundation for clinical 
      application. Methods: We conducted a systematic review of the meta-analysis using 
      eight databases and two clinical trial websites searching for randomized 
      controlled trials (RCTs) from conception to 15 March 2022, based on outcomes of 
      patients with RA treated with IGU. The evidence quality assessment of primary 
      outcomes was evaluated by the GRADE tool, and RevMan 5.3 and StataMP 14.0 were 
      used to perform this research. Results: A total of 4302 patients with RA from 38 
      RCTs was included in this research. Pooled results demonstrated as follows: 1) 
      Compared with methotrexate (MTX) alone, IGU alone was superior in improving ACR20 
      and DAS28-ESR, while having no significant difference in ACR50 and ACR70 [ACR20: 
      (RR 1.15, 95% CI 1.05-1.27, p = 0.004); ACR50: (RR 0.97, 95% CI 0.66-1.44, p = 
      0.88); ACR70: (RR 0.92, 95% CI 0.45-1.90, p = 0.83); DAS28-ESR: mean difference 
      (MD) -0.15, 95% CI -0.27 to -0.03, p = 0.01]. 2) Compared with MTX alone, IGU + 
      MTX was more effective in improving ACR20, ACR50, ACR70, and DAS28-ESR. [ACR20: 
      (RR 1.24, 95% CI 1.14-1.35, p < 0.00001); ACR50: (RR 1.96, 95% CI 1.62-2.39, p 
      <0.00001); ACR70: (RR 1.91, 95% CI 1.41-2.57, p < 0.0001)]; [DAS28-ESR: (MD) 
      -1.43, 95% CI -1.73 to -1.12, p < 0.00001]. 3) Compared with MTX + leflunomide 
      (LEF), ACR20, ACR50, ACR70, and DAS28-ESR of IGU + MTX had no significant 
      difference [ACR20: (RR 1.06, 95% CI 0.94-1.19, p = 0.38); ACR50: (RR 1.10, 95% CI 
      0.66-1.84, p = 0.72); ACR70: (RR 1.20, 95% CI 0.45-3.20, p = 0.71); DAS28-ESR: 
      (MD -0.02, 95% CI -0.13 to -0.10, p = 0.77)]. 4) Compared with MTX + 
      hydroxychloroquine (HCQ), IGU + MTX was superior in improving DAS28-ESR (MD 
      -2.16, 95% CI -2.53 to -1.79, p < 0.00001). 5) Compared with MTX + tripterygium 
      glycosides (TGs), IGU + MTX was more effective in improving DAS28-ESR (MD -0.94, 
      95% CI -2.36 to 0.48, p = 0.19). 6) There were no significant differences in 
      adverse events (AEs) between the groups of IGU vs. MTX (RR 0.96, 95% CI 
      0.71-1.31, p = 0.80), IGU + MTX vs. MTX (RR 1.10, 95% CI 0.90-1.35, p = 0.34), 
      IGU + MTX vs. MTX + HCQ (RR 0.64, 95% CI 0.29-1.42, p = 0.27), and IGU + MTX vs. 
      MTX + TGs (RR 0.75, 95% CI 0.28-2.02, p = 0.57). The incidence of AEs in the IGU 
      + MTX group was lower than the MTX + LEF group (RR 0.83, 95% CI 0.71-0.98, p = 
      0.03). Conclusion: Compared to the MTX alone subgroup, IGU alone offers clear 
      advantages in improving ACR20 and DAS28-ESR, despite the insufficient evidence 
      for DAS28-ESR findings. IGU + MTX shows clear benefits in improving ACR20, ACR50, 
      ACR70, and DAS28-ESR scores compared to standard therapies. When the intervention 
      (IGU alone or IGU + MTX) lasted for 52 weeks, it demonstrated superior efficacy 
      in improving ACR20 of patients without prominent adverse events. Notably, IGU or 
      IGU + MTX has apparent advantages in improving ACR20 of first-visit RA, and IGU + 
      MTX has obvious advantages in improving DAS28-ESR of refractory RA. Furthermore, 
      IGU + MTX does not increase the risk of leukopenia, but it can decrease the risk 
      of liver function tests (LFTs), regardless of the age or the stage of RA. 
      Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, 
      identifier CRD42022295217.
CI  - Copyright (c) 2022 Ouyang, Ma, Zou, Wang, Chen, Yang, Zou, Li and Cao.
FAU - Ouyang, Dan
AU  - Ouyang D
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
AD  - Hunan Provincial Key Laboratory of Diagnostics in Chinese Medicine, Hunan 
      University of Chinese Medicine, Changsha, China.
FAU - Ma, Yuan Zhi
AU  - Ma YZ
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Zou, Jie
AU  - Zou J
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Wang, Yong Long
AU  - Wang YL
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Chen, Zheng
AU  - Chen Z
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
FAU - Yang, Yu Ying
AU  - Yang YY
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
AD  - Hunan Provincial Key Laboratory of Diagnostics in Chinese Medicine, Hunan 
      University of Chinese Medicine, Changsha, China.
FAU - Zou, Bin
AU  - Zou B
AD  - General Surgery Department, University of South China Affiliated Changsha Central 
      Hospital, Changsha, China.
FAU - Li, Xin
AU  - Li X
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
AD  - Hunan Provincial Key Laboratory of Diagnostics in Chinese Medicine, Hunan 
      University of Chinese Medicine, Changsha, China.
FAU - Cao, Jian Zhong
AU  - Cao JZ
AD  - School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 
      China.
AD  - Hunan Provincial Key Laboratory of Diagnostics in Chinese Medicine, Hunan 
      University of Chinese Medicine, Changsha, China.
LA  - eng
PT  - Systematic Review
DEP - 20220805
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9389904
OTO - NOTNLM
OT  - iguratimod
OT  - meta-analysis
OT  - methotrexate
OT  - rheumatoid arthritis
OT  - systematic review
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/23 06:00
MHDA- 2022/08/23 06:01
PMCR- 2022/08/05
CRDT- 2022/08/22 04:18
PHST- 2022/04/03 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/08/22 04:18 [entrez]
PHST- 2022/08/23 06:00 [pubmed]
PHST- 2022/08/23 06:01 [medline]
PHST- 2022/08/05 00:00 [pmc-release]
AID - 911810 [pii]
AID - 10.3389/fphar.2022.911810 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 5;13:911810. doi: 10.3389/fphar.2022.911810. 
      eCollection 2022.