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Background Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis RA remain symptomatic. However, uniform terminology and an appropriate definition are lacking. Herein, we present the definition of difficult-to-treat RA, as the first step. Methods The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached assessed through voting. Conclusions The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research. You will be able to get a quick price and instant permission to reuse the content in many different ways. The treat-to-target T2T strategy advises an agreed disease activity target, remission or at least low disease activity, that can in turn inform responsive treatment escalation. A recent international survey of rheumatologists highlighted the perceived management problems and features in this patient category; the results of which confirmed the unmet need of this subpopulation of RA patients. Uniform terminology and a clear definition for this patient group are lacking. In the current literature, different terms are used to describe this subpopulation of RA patients, for example, severe, refractory, resistant to multiple drugs or treatments, established and difficult-to-treat. The Task Force comprises 32 individuals including the Steering Committee members of which 25 members were present at the first Task Force meeting, which took place in August All rheumatologists are experienced in the treatment of RA, the majority with significant experience in clinical trials and a proportion in outcomes research. Numerous Task Force members have a leading role in organising and evaluating patient registries. All Task Force members declared their potential conflicts of interest before the start of the project. How many RA patients do you treat? The Steering Committee created the first draft of the definition based on the results of the survey and on a scoping literature search that was performed to explore different definitions that currently have been used by NMTR, MJHdH and PMJW, see, online supplemental material 1. The results of the survey, the proposed terminology and the draft definition were presented to the Task Force at the first Task Force meeting. After the presentation of the draft terminology and definition, the general concepts were discussed and amended. Thereafter, the detailed wording was discussed and amended until consensus was reached. A voting process was conducted for each item of the terminology and definition. In case no consensus was reached among the present Task Force members, the preferred version was selected by voting. Twenty-one Task Force members were present during this discussion and voting process. After the meeting, two versions of the definition were distributed among all Task Force members to select the final version. None of these terms was deemed to cover the wide range of possible clinical scenarios which may be relevant for this patient population. Thereafter, we sought to create a definition of D2T RA based on the results of the previously mentioned international survey 8 and expert opinions. All three criteria need to be present to confirm the state of D2T RA. Consequently, it was decided to select this cut-off by the Task Force. In addition to clinical signs and symptoms, it was agreed that this clarification should also include imaging and biochemical markers suggestive of active disease. Furthermore, all Task Force members agreed that not only patients with joint-related problems should qualify to be defined as being D2T. Extra-articular manifestations, such as vasculitis, pericarditis, scleritis or glomerulonephritis may complicate the management of RA, and were therefore decided to be included in the definition. During the Task Force meeting, additional possible signs of active disease were explicitly suggested for inclusion in the definition. First, the Task Force agreed to include rapid radiographic progression in the definition as a possible feature of D2T RA, as this might be occasionally observed even in case of clinically inactive disease. Second, non-inflammatory disease was considered, since these complaints, for example, concomitant fibromyalgia, might mimic inflammatory activity. Furthermore, non-inflammatory disease might also lead to other clinically important complaints. The Task Force discussed whether to add fatigue to the definition, as this is one of the most common problems. This suggests that only clinical scenarios which are judged as problematic eg, apparently ineffective treatment are referred to as D2T RA. There were some concerns that this criterion might be too subjective, especially for research. However, the focus of the recommendations should be on the clinical implications, which supports to include this criterion. Inability to taper glucocorticoid treatment below 7. Well-controlled disease according to above standards, but still having RA symptoms that are causing a reduction in quality of life. The treatment of the heterogeneous patient population that comprises D2T RA is often a clinical challenge for which practical management recommendations are needed. Several factors may complicate the management of these patients. On the other hand, concomitant syndromes or diseases, such as fibromyalgia, osteoarthritis and psychosocial factors associated with poor coping, can result in non-inflammatory symptoms eg, pain that can mimic inflammatory activity and therewith contribute to D2T RA. These will include both pharmacological and non-pharmacological treatment options and will be complementary to the existing RA recommendations. These elements were selected based on the results of the survey. The acceptable GC dose for chronic use remains a matter of discussion, although there is a significant group of RA patients that is treated with GCs long-term. We realise that lower GC doses were suggested by other EULAR Task Forces, on the other hand, we believe that less stringent criteria will be more realistic to define the D2T patients, as inability to follow these criteria can indicate a management problem. The Task Force felt that not only patients fulfilling criterion 1 and 3 with inflammatory activity should be able to be classified as having D2T RA, but also those patients with non-inflammatory complaints. Coexisting non-inflammatory conditions may lead to a high clinical burden. There are some limitations of this work. The definition of D2T RA needs to be validated. A further complicating factor might be that, as also apparent from the definition, this patient group is rather heterogeneous and hence difficult to capture in one definition. In conclusion, the principal goal of RA management is to achieve sustained remission or at least low disease activity following steps of the current EULAR recommendations. Hopefully, the definition presented here will provide a robust and consistent identification of patients with D2T RA. In addition, this definition can provide a platform to define a group of similar patients for research. Further work is underway to provide detailed recommendations for the management of D2T RA. The Task Force acknowledges the contribution of Maria J H de Hair, rheumatology postdoctoral fellow who left the Task Force due to her new position in the pharma industry. All authors participated in the work of the Task Force and provided coauthor contribution to the manuscript. All authors read and approved the final manuscript. Competing interests All participants provided declaration of interest, the individual declarations are attached as online supplemental file 2. Refer to the Methods section for further details. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement All data relevant to the study are included in the article or uploaded as online supplemental file 1. Skip to main content. Log in via OpenAthens. Log in using your username and password For personal accounts OR managers of institutional accounts. Forgot your log in details? Register a new account? Forgot your user name or password? Search for this keyword. Advanced search. Log in via Institution. Email alerts. Article Text. Article menu. EULAR definition of difficult-to-treat rheumatoid arthritis. Abstract Background Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis RA remain symptomatic. Statistics from Altmetric. Supplemental material \[annrheumdissupp Agreement process After the presentation of the draft terminology and definition, the general concepts were discussed and amended. Definition Thereafter, we sought to create a definition of D2T RA based on the results of the previously mentioned international survey 8 and expert opinions. Rapid radiographic progression with or without signs of active disease. All three criteria need to be present in D2T RA. Discussion The treatment of the heterogeneous patient population that comprises D2T RA is often a clinical challenge for which practical management recommendations are needed. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: update. Ann Rheum Dis ; 79 : — Arthritis Rheumatol ; 68 : 1 — OpenUrl PubMed. Treating rheumatoid arthritis to target: update of the recommendations of an international Task force. Ann Rheum Dis ; 75 : 3 — Biologic refractory disease in rheumatoid arthritis: results from the British Society for rheumatology biologics register for rheumatoid arthritis. Ann Rheum Dis ; 77 : — Difficult-To-Treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology ; 57 : — Risk profiling for a refractory course of rheumatoid arthritis. Semin Arthritis Rheum ; 49 : — 5. Buch MH. Defining refractory rheumatoid arthritis. Ann Rheum Dis ; 77 : — 9. Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey. Systematic assessment of difficult-to-treat asthma. Eur Respir J ; 22 : — Thase ME. Therapeutic alternatives for difficult-to-treat depression: a narrative review of the state of the evidence. CNS Spectr ; 9 : — Difficult-To-Treat or resistant hypertension: etiology, pathophysiology, and innovative therapies. Int J Hypertens ; : 1 — 4. Biologic interventions for fatigue in rheumatoid arthritis. Role of sleep disturbance, depression, obesity, and physical inactivity in fatigue in rheumatoid arthritis. Arthritis Care Res ; 68 : 81 — Twenty-eight-joint counts invalidate the DAS28 remission definition owing to the omission of the lower extremity joints: a comparison with the original DAS remission. Ann Rheum Dis ; 65 : — Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR Task force. Ann Rheum Dis ; 75 : — 7. Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort. Arthritis Res Ther ; 14 : R Patient consent for publication Not required. Read the full text or download the PDF:. Log in.

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