PMID- 35921745
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220922
IS  - 1532-866X (Electronic)
IS  - 0049-0172 (Linking)
VI  - 56
DP  - 2022 Oct
TI  - Clinical prediction models for methotrexate treatment outcomes in patients with 
      rheumatoid arthritis: A systematic review and meta-analysis.
PG  - 152076
LID - S0049-0172(22)00127-5 [pii]
LID - 10.1016/j.semarthrit.2022.152076 [doi]
AB  - BACKGROUND: In the management of rheumatoid arthritis (RA), there is a clinical 
      need to identify which patients are at high-risk of not responding to 
      methotrexate (MTX), or experiencing adverse events (AEs), to enable earlier 
      alternative treatments. Many clinical prediction models (CPMs) have previously 
      been developed, but a summary of such models and their methodological quality is 
      lacking. This systematic review aimed to (i) identify and summarize previously 
      published CPMs of MTX outcomes in biologic-naive RA patients, and (ii) critically 
      appraise their methodological properties. METHODS: Medline and Embase were 
      searched to identify studies developing or validating CPMs of MTX outcomes in RA 
      patients. The risk of bias (ROB) was assessed using PROBAST (prediction model 
      risk of bias assessment tool). A fixed effects meta-analysis summarised 
      discrimination for models with multiple external validations. RESULTS: The 
      systematic review identified 20 CPMs across 13 studies, and 4 validation studies. 
      Three outcome types were used: a state of disease activity (n = 14, 70%); EULAR 
      response criteria (n = 4, 20%); or discontinuation due to AEs (n = 2, 10%). Only 
      one model accounted for potential competing risks, and nine (45%) were internally 
      validated. Eight (40%) models used multiple imputation for missing data, others 
      were often limited to complete case analysis. There was overall high ROB. The 
      meta-analysis summarised c-statistics for two models with multiple external 
      validations was 0.77 (95% CI: 0.69, 0.84) and 0.68 (0.64, 0.71). CONCLUSION: This 
      review highlights several methodological shortcomings that should be addressed in 
      future model development to increase potential for implementation into practice.
CI  - Copyright (c) 2022. Published by Elsevier Inc.
FAU - Gehringer, Celina K
AU  - Gehringer CK
AD  - Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and 
      Dermatological Sciences, Manchester Academic Health Science Centre, University of 
      Manchester, Stopford Building, Oxford Road, Manchester M13 9PG, UK. Electronic 
      address: celina.gehringer@postgrad.manchester.ac.uk.
FAU - Martin, Glen P
AU  - Martin GP
AD  - Centre for Health Informatics, Division of Informatics, Imaging and Data 
      Sciences, University of Manchester, Manchester, UK.
FAU - Hyrich, Kimme L
AU  - Hyrich KL
AD  - Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and 
      Dermatological Sciences, Manchester Academic Health Science Centre, University of 
      Manchester, Stopford Building, Oxford Road, Manchester M13 9PG, UK; NIHR 
      Manchester Biomedical Research Centre, Manchester NHS Foundation Trust, 
      Manchester Academic Health Science Centre, Manchester, UK.
FAU - Verstappen, Suzanne M M
AU  - Verstappen SMM
AD  - Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and 
      Dermatological Sciences, Manchester Academic Health Science Centre, University of 
      Manchester, Stopford Building, Oxford Road, Manchester M13 9PG, UK; NIHR 
      Manchester Biomedical Research Centre, Manchester NHS Foundation Trust, 
      Manchester Academic Health Science Centre, Manchester, UK.
FAU - Sergeant, Jamie C
AU  - Sergeant JC
AD  - Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and 
      Dermatological Sciences, Manchester Academic Health Science Centre, University of 
      Manchester, Stopford Building, Oxford Road, Manchester M13 9PG, UK; Centre for 
      Biostatistics, Manchester Academic Health Science Centre, University of 
      Manchester, Manchester, UK.
LA  - eng
GR  - 21,755/VAC_/Versus Arthritis/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20220727
PL  - United States
TA  - Semin Arthritis Rheum
JT  - Seminars in arthritis and rheumatism
JID - 1306053
RN  - 0 (Antirheumatic Agents)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - *Antirheumatic Agents/therapeutic use
MH  - *Arthritis, Rheumatoid/chemically induced/drug therapy
MH  - Humans
MH  - Methotrexate/therapeutic use
MH  - Models, Statistical
MH  - Prognosis
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Clinical prediction model
OT  - Meta-analysis
OT  - Methotrexate
OT  - Rheumatoid arthritis
OT  - Systematic review
OT  - Treatment outcome
COIS- Declaration of Competing Interest KLH has received speaker honoraria from Abbvie 
      and grant income from BMS and Pfizer. The remaining authors have no conflicts of 
      interest to declare.
EDAT- 2022/08/04 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/08/03 18:18
PHST- 2022/06/20 00:00 [received]
PHST- 2022/07/22 00:00 [revised]
PHST- 2022/07/26 00:00 [accepted]
PHST- 2022/08/04 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/08/03 18:18 [entrez]
AID - S0049-0172(22)00127-5 [pii]
AID - 10.1016/j.semarthrit.2022.152076 [doi]
PST - ppublish
SO  - Semin Arthritis Rheum. 2022 Oct;56:152076. doi: 10.1016/j.semarthrit.2022.152076. 
      Epub 2022 Jul 27.