Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan;7(1):e001511.
doi: 10.1136/rmdopen-2020-001511.

Diagnostic issues in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis

Nadia M T Roodenrijs  1 , Melinda Kedves  2 , Attila Hamar  3 , György Nagy  4   5 , Jacob M van Laar  6 , Désirée van der Heijde  7 , Paco M J Welsing  6
Affiliations

Diagnostic issues in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis

Nadia M T Roodenrijs et al. RMD Open. 2021 Jan.

Abstract

Objectives: To summarise the evidence on diagnostic issues in difficult-to-treat rheumatoid arthritis (D2T RA) informing the EULAR recommendations for the management of D2T RA.

Methods: A systematic literature review (SLR) was performed regarding the optimal confirmation of a diagnosis of rheumatoid arthritis (RA) and of mimicking diseases and the assessment of inflammatory disease activity. PubMed and Embase databases were searched up to December 2019. Relevant papers were selected and appraised.

Results: Eighty-two papers were selected for detailed assessment. The identified evidence had several limitations: (1) no studies were found including D2T RA patients specifically, and only the minority of studies included RA patients in whom there was explicit doubt about the diagnosis of RA or presence of inflammatory activity; (2) mostly only correlations were reported, not directly useful to evaluate the accuracy of detecting inflammatory activity in clinical practice; (3) heterogeneous, and often suboptimal, reference standards were used and (4) (thus) only very few studies had a low risk of bias.To ascertain a diagnosis of RA or relevant mimicking disease, no diagnostic test with sufficient validity and accuracy was identified. To ascertain inflammatory activity in patients with RA in general and in those with obesity and fibromyalgia, ultrasonography (US) was studied most extensively and was found to be the most promising diagnostic test.

Conclusions: This SLR highlights the scarcity of high-quality studies regarding diagnostic issues in D2T RA. No diagnostic tests with sufficient validity and accuracy were found to confirm nor exclude the diagnosis of RA nor its mimicking diseases in D2T RA patients. Despite the lack of high-quality direct evidence, US may have an additional value to assess the presence of inflammatory activity in D2T RA patients, including those with concomitant obesity or fibromyalgia.

Keywords: arthritis; rheumatoid; synovitis; ultrasonography.

PubMed Disclaimer

Conflict of interest statement

Competing interests: NMTR, MK, AH and PMJW declare to have no competing interests. GN received fees from Amgen, AbbVie, BMS, Boehringer Ingelheim, Janssen, KRKA, Merck, MSD, Novartis, Pfizer, Roche, UCB; research grants from Pfizer, AbbVie. JMvL reports personal fees from Arxx Tx, Gesyntha, Magenta, Sanofi Genzyme, Leadiant, Boehringer-Ingelheim, Galapagos; grants and personal fees from Roche; grants from Astra Zeneca, MSD, Thermofisher. DvdH received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB. All competing interests are outside the submitted work.

Figures

Figure 1
Figure 1
Flow charts of search and selection of papers. (A) (Mis-)diagnosis of RA and relevant differential diagnoses. (B) The assessment of inflammatory activity in (2a) RA patients, and (2b) RA patients with comorbidities that might influence the assessment. RA, rheumatoid arthritis; SLR, systematic literature review.
See this image and copyright information in PMC

References

    1. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79:685–99. 10.1136/annrheumdis-2019-216655 - DOI - PubMed
    1. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1–26. 10.1002/art.39480 - DOI - PubMed
    1. Buch MH Defining refractory rheumatoid arthritis. Ann Rheum Dis 2018;77:966–9. 10.1136/annrheumdis-2017-212862 - DOI - PubMed
    1. de Hair MJH, Jacobs JWG, Schoneveld JLM, et al. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology 2018;57:1135–44. 10.1093/rheumatology/kex349 - DOI - PubMed
    1. Kearsley-Fleet L, Davies R, De Cock D, et al. Biologic refractory disease in rheumatoid arthritis: results from the British Society for rheumatology biologics register for rheumatoid arthritis. Ann Rheum Dis 2018;77:1405–12. 10.1136/annrheumdis-2018-213378 - DOI - PMC - PubMed

Publication types

LinkOut - more resources