Fraenkel L, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924–39.
Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
Article PubMed CAS Google Scholar
Felson DT, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63(3):573–86.
Article PubMed PubMed Central Google Scholar
Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis. 2018;77(7):966–9.
Article PubMed CAS Google Scholar
Kearsley-Fleet L, 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(10):1405–12.
O’Reilly TJ. Azathioprine in the treatment of refractory rheumatoid arthritis. Ir Med J. 1977;70(11):344–6.
de Bosset PL, Biter T. Near-cytotoxic gold salt therapy in long standing drug-refractory rheumatoid arthritis. A prospective investigation. Schweiz Med Wochenschr. 1973;103(33):1153–8.
Nordstrom D. Rheumatoid arthritis refractory to standard therapy. JAMA. 1988;260(9):1241.
Article PubMed CAS Google Scholar
• Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021;80(1):31–5. This is the first consensus on a definition for D2T RA, which is an important step forward for future study of this unique disease subset.
de Hair MJH, et al. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology (Oxford). 2018;57(7):1135–44.
Roodenrijs NMT, et al. Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis. RMD Open. 2021;7(1):e001512.
Article PubMed PubMed Central Google Scholar
Roodenrijs NMT, et al. 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. RMD Open. 2021;7(1):e001511.
Article PubMed PubMed Central Google Scholar
Roodenrijs NMT, et al. Non-adherence in difficult-to-treat rheumatoid arthritis from the perspectives of patients and rheumatologists: a concept mapping study. Rheumatology (Oxford). 2021;60(11):5105–16.
• Roodenrijs NMT, et al. Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search. Rheumatology (Oxford). 2022;61(9):3552–66. This comprehensive review of possible immune mechanisms driving the development of D2T RA addresses the complexity of this syndrome.
Article PubMed CAS Google Scholar
Ochi S, et al. Difficult-to-treat rheumatoid arthritis with respect to responsiveness to biologic/targeted synthetic DMARDs: a retrospective cohort study from the FIRST registry. Clin Exp Rheumatol. 2022;40(1):86–96.
Novella-Navarro M, et al. A paradigm of difficult-to-treat rheumatoid arthritis: subtypes and early identification. Clin Exp Rheumatol. 2022. https://doi.org/10.55563/clinexprheumatol/7mscci.
Messelink MA, et al. Identification and prediction of difficult-to-treat rheumatoid arthritis patients in structured and unstructured routine care data: results from a hackathon. Arthritis Res Ther. 2021;23(1):184.
Article PubMed PubMed Central Google Scholar
• Buch MH, Eyre S, McGonagle D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021;17(1):17–33. The authors have identified key similarities and differences between those with RA who have persistent symptoms, but who have and do not have objective evidence of ongoing inflammatory disease activity. This clearly represents a key clinical challenge and an area in need of future research focus.
Becede M, et al. Risk profiling for a refractory course of rheumatoid arthritis. Semin Arthritis Rheum. 2019;49(2):211–7.
Fitton J, et al. Single-centre experience of refractory rheumatoid arthritis. Rheumatol Adv Pract. 2022;6(2):rkac057.
Article PubMed PubMed Central Google Scholar
Watanabe R, et al. Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort. Immunol Med. 2022;45(1):35–44.
Article PubMed CAS Google Scholar
Takanashi S, Kaneko Y, Takeuchi T. Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice. Rheumatology (Oxford). 2021;60(11):5247–56.
Article PubMed CAS Google Scholar
Albrecht K, Zink A. Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies. Arthritis Res Ther. 2017;19(1):68.
Article PubMed PubMed Central Google Scholar
Anderson J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken). 2012;64(5):640–7.
England BR, et al. 2019 Update of the American College of Rheumatology Recommended Rheumatoid Arthritis Disease Activity Measures. Arthritis Care Res (Hoboken). 2019;71(12):1540–55.
Lee YC, et al. Incidence and predictors of secondary fibromyalgia in an early arthritis cohort. Ann Rheum Dis. 2013;72(6):949–54.
Joharatnam N, et al. A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis. Arthritis Res Ther. 2015;17(1):11.
Article PubMed PubMed Central Google Scholar
Ton E, et al. Look beyond the disease activity score of 28 joints (DAS28): tender points influence the DAS28 in patients with rheumatoid arthritis. J Rheumatol. 2012;39(1):22–7.
Ferreira RJO, et al. Suppressing inflammation in rheumatoid arthritis: does patient global assessment blur the target? A practice-based call for a paradigm change. Arthritis Care Res (Hoboken). 2018;70(3):369–78.
Holdsworth EA, et al. Biologic and targeted synthetic DMARD utilization in the United States: Adelphi Real World disease specific programme for rheumatoid arthritis. Rheumatol Ther. 2021;8(4):1637–49.
Article PubMed PubMed Central Google Scholar
Backhaus M, et al. Arthritis of the finger joints: a comprehensive approach comparing conventional radiography, scintigraphy, ultrasound, and contrast-enhanced magnetic resonance imaging. Arthritis Rheum. 1999;42(6):1232–45.
Article PubMed CAS Google Scholar
Dougados M, et al. The ability of synovitis to predict structural damage in rheumatoid arthritis: a comparative study between clinical examination and ultrasound. Ann Rheum Dis. 2013;72(5):665–71.
Kane D, Balint PV, Sturrock RD. Ultrasonography is superior to clinical examination in the detection and localization of knee joint effusion in rheumatoid arthritis. J Rheumatol. 2003;30(5):966–71.
Moller-Bisgaard S, et al. Effect of magnetic resonance imaging vs conventional treat-to-target strategies on disease activity remission and radiographic progression in rheumatoid arthritis: The IMAGINE-RA randomized clinical trial. JAMA. 2019;321(5):461–72.
Article PubMed PubMed Central Google Scholar
Haavardsholm EA, et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ. 2016;354:i4205.
Article PubMed PubMed Central Google Scholar
Roodenrijs NMT, et al. Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey. Ann Rheum Dis. 2018;77(12):1705–9.
Article PubMed CAS Google Scholar
Tan Y, Buch MH. “Difficult to treat” rheumatoid arthritis: current position and considerations for next steps. RMD Open. 2022;8(2):e002387.
Article PubMed PubMed Central Google Scholar
Khader Y, et al. Predictors of remission in rheumatoid arthritis patients treated with biologics: a systematic review and meta-analysis. Clin Rheumatol. 2022;41(12):3615–27.
Article PubMed PubMed Central Google Scholar
Giollo A, et al. Early characterisation of difficult-to-treat rheumatoid arthritis by suboptimal initial management A multicentre cohort study. Rheumatology (Oxford). 2022;62:2083–9.
Leon L, et al. Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease. RMD Open. 2023;9(1):e002842.
Comments (0)