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Prediction of response to anti-TNF treatment using laboratory biomarkers in patients with rheumatoid arthritis: a systematic review
Open accessAbstract
Objectives: In this systematic review, we aim to identify laboratory biomarkers that predict response to tumour necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA). Methods: EMBASE, PubMed and Cochrane Library (CENTRAL) were searched for studies that presented predictive accuracy measures of laboratory biomarkers, or in which these were calculable. Likelihood ratios were calculated in order to determine whether a test result relevantly changed the probability of response. Likelihood ratios between 2–10 and 0.5–0.1 were considered weak predictors, respectively, and ratios above 10 or below 0.1 were considered strong predictors of response. Primary focus was on biomarkers studied ≥3 times. Results: From 41 included studies, data on 99 different biomarkers were extracted. Five biomarkers were studied ≥3 times, being (1) anti-cyclic citrullinated peptide (CCP), (2) rheumatoid factor, (3) –308 polymorphism in the TNF-α gene, (4) SE copies in the HLA-DRB1 gene and (5) FcGR2A polymorphism. No studies showed a strong predictive association and only one study on anti-CCP showed a weak positive association. Conclusions: No biomarkers were found that consistently showed a (strong) predictive effect for response to TNFi in patients with RA. Given the disappointing yield of previous predictive biomarker research, future studies should focus on exploring, combining and validating the most promising laboratory biomarkers identified in this review, and searching for new predictors. Besides this, they should focus on contexts where prediction-aided decision-making can have a large impact (even with limited predictive value of markers/models). PROSPERO registration number: CRD42021278987.
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“Despite several attempts, including machine learning utilisation,42–44 no single established biomarker has been reported in a real-life setting.45”
From Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study (2024) · cites this paper as [45]
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“45 Finally, the lack of noteworthy changes of diurnal production of saliva cortisol over time, in spite of the significant treatment-induced changes in disease activity and degree of stress, provides additional evidence that the impaired adrenal reserve in RA is probably an intrinsic condition…”
Background
Metadata
- Authors
- Wientjes, M. H. M., den Broeder, A. A., Welsing, P. M. J., Verhoef, L. M., & van den Bemt, B. J. F.
- Affiliations
- Radboud University Nijmegen (NL)
- University Medical Center Utrecht (NL)
- Sint Maartenskliniek (NL)
- Corresponding author
- Wientjes, Maike H M
- Venue
- RMD Open
- Publisher
- BMJ
- Published
- 2022-12
- Volume
- 8
- Issue
- 2
- Pages
- e002570
- ISSN
- 2056-5933 (ISSN-L)
- PMC
- PMC9730399
- OpenAlex
- W4310747330
- Cited by
- 18
- References
- 38
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- RMD Open (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- rheumatoid arthritis, tumor necrosis factor inhibitors, predictive biomarkers, laboratory biomarkers, anti-CCP antibodies, rheumatoid factor, TNF-α -308 polymorphism, likelihood ratios, treatment response prediction
- MeSH terms
- Tumor Necrosis Factor Inhibitors, Arthritis, Rheumatoid, Autoantibodies, Humans, Rheumatoid Factor, Biomarkers, Antirheumatic Agents
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