PMID- 33909898
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20231107
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 60
IP  - 9
DP  - 2021 Sep 1
TI  - Prevalence and predictors of adverse events with methotrexate mono- and 
      combination-therapy for rheumatoid arthritis: a systematic review.
PG  - 4001-4017
LID - 10.1093/rheumatology/keab304 [doi]
AB  - OBJECTIVES: This systematic review aims to summarize rates of adverse events 
      (AEs) in patients with RA or inflammatory arthritis starting MTX as monotherapy 
      or in combination with other csDMARDs, and to identify reported predictors of 
      AEs. METHODS: Three databases were searched for studies reporting AEs in 
      MTX-naive patients with RA. Randomized controlled trials (RCTs) and observational 
      cohort studies were included. Prevalence rates of AEs were pooled using random 
      effects meta-analysis, stratified by study design. RESULTS: Forty-six articles 
      (34 RCTs and 12 observational studies) were identified. The pooled prevalence of 
      total AEs was 80.1% in RCTs (95% CI: 73.5, 85.9), compared with 23.1% in 
      observational studies (95% CI: 12.3, 36.0). The pooled prevalence of serious AEs 
      was 9.5% in RCTs (95% CI: 7.4, 11.7), and 2.1% in observational studies (95% CI: 
      1.0, 3.4). MTX discontinuation due to AEs was higher in observational studies 
      (15.5%, 95% CI: 9.6, 22.3) compared with RCTs (6.7%, 95% CI: 4.7, 8.9). 
      Gastrointestinal events were the most commonly reported AEs (pooled prevalence: 
      32.7%, 95% CI: 18.5, 48.7). Five studies examined predictors of AEs. RF status, 
      BMI and HAQ score were associated with MTX discontinuation due to AEs; ACPA 
      negativity, smoking and elevated creatinine were associated with increased risk 
      of elevated liver enzymes. CONCLUSION: The review provides an up-to-date overview 
      of the prevalence of AEs associated with MTX in patients with RA. The findings 
      should be communicated to patients to help them make informed choices prior to 
      commencing MTX.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      British Society for Rheumatology. All rights reserved. For permissions, please 
      email: journals.permissions@oup.com.
FAU - Sherbini, Ahmad A
AU  - Sherbini AA
AUID- ORCID: 0000-0002-7554-0752
AD  - Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, 
      Division of Musculoskeletal and Dermatological Sciences, The University of 
      Manchester.
FAU - Sharma, Seema D
AU  - Sharma SD
AD  - Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, 
      Division of Musculoskeletal and Dermatological Sciences, The University of 
      Manchester.
FAU - Gwinnutt, James M
AU  - Gwinnutt JM
AUID- ORCID: 0000-0002-1435-8797
AD  - Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, 
      Division of Musculoskeletal and Dermatological Sciences, The University of 
      Manchester.
FAU - Hyrich, Kimme L
AU  - Hyrich KL
AUID- ORCID: 0000-0001-8242-9262
AD  - Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, 
      Division of Musculoskeletal and Dermatological Sciences, The University of 
      Manchester.
AD  - NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation 
      Trust, Manchester Academic Health Science Centre, Manchester, UK.
FAU - Verstappen, Suzanne M M
AU  - Verstappen SMM
AD  - Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, 
      Division of Musculoskeletal and Dermatological Sciences, The University of 
      Manchester.
AD  - NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation 
      Trust, Manchester Academic Health Science Centre, Manchester, UK.
LA  - eng
GR  - 20385/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Antirheumatic Agents)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Antirheumatic Agents/*adverse effects
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Methotrexate/*adverse effects
MH  - Prevalence
MH  - Risk Factors
PMC - PMC8410011
OTO - NOTNLM
OT  - adverse event
OT  - methotrexate
OT  - pooled proportions
OT  - predictor
OT  - rheumatoid arthritis
EDAT- 2021/04/29 06:00
MHDA- 2021/10/05 06:00
PMCR- 2022/04/28
CRDT- 2021/04/28 17:39
PHST- 2020/10/31 00:00 [received]
PHST- 2021/03/21 00:00 [revised]
PHST- 2021/04/29 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/04/28 17:39 [entrez]
PHST- 2022/04/28 00:00 [pmc-release]
AID - 6257447 [pii]
AID - keab304 [pii]
AID - 10.1093/rheumatology/keab304 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2021 Sep 1;60(9):4001-4017. doi: 
      10.1093/rheumatology/keab304.