PMID- 36248913
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230330
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Comparative efficacy and safety of JAK inhibitors as monotherapy and in 
      combination with methotrexate in patients with active rheumatoid arthritis: A 
      systematic review and meta-analysis.
PG  - 977265
LID - 10.3389/fimmu.2022.977265 [doi]
LID - 977265
AB  - BACKGROUND: We aim to evaluate the efficacy and tolerability of Janus kinase 
      inhibitors (JAKi) as monotherapy and in combination with methotrexate (MTX) in 
      active rheumatoid arthritis (RA). METHODS: Medline, EMBASE, and Cochrane Library 
      were systematically searched to identify relevant randomized controlled trials 
      (RCTs). Pooled analysis was conducted using random-effects model, along with the 
      risk difference (RD) and 95% confidence intervals (CIs). RESULTS: Three RCTs, 
      including 2,290 patients, were included. JAKi (tofacitinib, baricitinib, and 
      filgotinib) plus MTX displayed a higher proportion of patients meeting the 
      American College of Rheumatology (ACR) criteria than JAKi alone at week 52 (ACR20 
      RD 0.032; 95% CI -0.027 to 0.091; ACR50 RD 0.050; 95% CI 0.003 to 0.097; ACR70 RD 
      0.056; 95% CI 0.012 to 0.100). Similar results were observed for ACR20/50/70 at 
      week 24. No significant difference was found between two regimens for the 
      proportion of patients achieving Health Assessment Questionnaire disability index 
      (HAQ-DI) improvement >/= 0.22 at weeks 24 and 52. Regarding low disease activity 
      and remission achievement, JAKi in combination with MTX, contributed higher 
      response rates than JAKi alone at weeks 24 and 52. Compared with JAKi 
      monotherapy, combination therapy had a higher risks of treatment-emergent adverse 
      events (TEAEs) and adverse events (AEs) leading to study discontinuation. 
      CONCLUSION: JAKi combined with MTX demonstrated superiority to JAKi monotherapy 
      in terms of ACR responses, low disease activity and remission achievement. The 
      two regimens presented comparable physical functioning measured by HAQ-DI 
      improvement and similar tolerability, except for high risks of TEAEs and AEs 
      leading to study discontinuation in combination therapy. SYSTEMATIC REVIEW 
      REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288907.
CI  - Copyright (c) 2022 Liu, Yan, Shi, Lin, Gu and Li.
FAU - Liu, Li
AU  - Liu L
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Yan, Yi-Dan
AU  - Yan YD
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Shi, Fang-Hong
AU  - Shi FH
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Lin, Hou-Wen
AU  - Lin HW
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
AD  - School of Medicine, Tongji University, Shanghai, China.
FAU - Gu, Zhi-Chun
AU  - Gu ZC
AD  - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Li, Jia
AU  - Li J
AD  - Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, China.
LA  - eng
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20220929
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Janus Kinase Inhibitors)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Humans
MH  - *Antirheumatic Agents/adverse effects
MH  - *Arthritis, Rheumatoid/chemically induced/drug therapy
MH  - *Janus Kinase Inhibitors/adverse effects
MH  - Methotrexate/adverse effects
PMC - PMC9556706
OTO - NOTNLM
OT  - combination therapy
OT  - janus kinase inhibitors
OT  - methotrexate
OT  - monotherapy
OT  - rheumatoid arthritis
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- 2022/10/18 06:00
MHDA- 2022/10/19 06:00
PMCR- 2022/01/01
CRDT- 2022/10/17 05:14
PHST- 2022/06/24 00:00 [received]
PHST- 2022/09/15 00:00 [accepted]
PHST- 2022/10/17 05:14 [entrez]
PHST- 2022/10/18 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.977265 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 29;13:977265. doi: 10.3389/fimmu.2022.977265. eCollection 
      2022.