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Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey
  1. Nadia M T Roodenrijs1,
  2. Maria J H de Hair1,
  3. Marlies C van der Goes1,
  4. Johannes W G Jacobs1,
  5. Paco M J Welsing1,
  6. Désirée van der Heijde2,
  7. Daniel Aletaha3,
  8. Maxime Dougados4,
  9. Kimme L Hyrich5,
  10. Iain B McInnes6,
  11. Ulf Mueller-Ladner7,
  12. Ladislav Senolt8,
  13. Zoltan Szekanecz9,
  14. Jacob M van Laar1,
  15. György Nagy10,11,
  16. On behalf of the whole EULAR Task Force on development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis
  1. 1 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
  2. 2 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
  4. 4 Department of Rheumatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris Descartes University, Paris, France
  5. 5 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  6. 6 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  7. 7 Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic Bad Nauheim, Bad Nauheim, Germany
  8. 8 Department of Rheumatology, 1st Faculty of Medicine, Charles University and Rheumatology Institute, Prague, Czech Republic
  9. 9 Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  10. 10 Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
  11. 11 Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
  1. Correspondence to Nadia M T Roodenrijs, Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands; N.M.T.Roodenrijs{at}


Objectives Patients with difficult-to-treat rheumatoid arthritis (RA) remain symptomatic despite treatment according to current European League Against Rheumatism (EULAR) management recommendations. These focus on early phases of the disease and pharmacological management. We aimed to identify characteristics of difficult-to-treat RA and issues to be addressed in its workup and management that are not covered by current management recommendations.

Methods An international survey was conducted among rheumatologists with multiple-choice questions on disease characteristics of difficult-to-treat RA. Using open questions, additional items to be addressed and items missing in current management recommendations were identified.

Results 410 respondents completed the survey: 50% selected disease activity score assessing 28 joints >3.2 OR presence of signs suggestive of active disease as characteristics of difficult-to-treat RA; 42% selected fatigue; 48% selected failure to ≥2 conventional synthetic disease-modifying antirheumatic drugs (DMARDs) AND ≥2 biological/targeted synthetic DMARDs; 89% selected inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering comorbidities, extra-articular manifestations and polypharmacy were identified as important issues missing in current management recommendations.

Conclusions There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations.

  • rheumatoid Arthritis
  • disease activity
  • treatment

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  • Handling editor Gerd R Burmester

  • Presented at This manuscript has been previously presented at EULAR 2018 (Roodenrijs NMT, de Hair MJH, Jacobs JWG, et al. OP0139 Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey (abstract). Ann Rheum Dis 2018;77:120.)

  • Contributors NMTR contributed to the data analysis, interpretation of data and manuscript preparation. MJHdH and JWGJ contributed to the design of the study, data analysis, interpretation of data and manuscript preparation. PMJW, DvdH and JMvL contributed to the design of the study, interpretation of data and manuscript preparation. MCVdG, DA, MD, KLH, IBM, UM-L, LS and ZS contributed to the acquisition of data and manuscript preparation. GN contributed to the design of the study, acquisition of data, interpretation of data and manuscript preparation. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests NMTR, MJHdH, MCvdG, JWGJ, PMJW, DA, MD, KLH, IBM, UM-L and ZS declare to have no competing interests. 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 and UCB. LS received fees from AbbVie, BMS, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Takeda and UCB. JMvL received fees from Arthrogene, MSD, Pfizer, Eli Lilly and BMS and research grants from Astra Zeneca and Roche-Genentech. GN received fees from Amgen, AbbVie, BMS, KRKA, MSD, Pfizer, Roche and UCB and research grants from Pfizer and AbbVie.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.