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Ann Rheum Dis. 2018 Dec;77(12):1705-1709. doi: 10.1136/annrheumdis-2018-213687. Epub 2018 Sep 7.

Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey.

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Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
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.
NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic Bad Nauheim, Bad Nauheim, Germany.
Department of Rheumatology, 1st Faculty of Medicine, Charles University and Rheumatology Institute, Prague, Czech Republic.
Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.



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.


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.


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.


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


disease activity; rheumatoid Arthritis; treatment

[Indexed for MEDLINE]

Conflict of interest statement

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.

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