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

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.Pathophysiology and treatment of rheumatic disease

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

Objectives To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.Methods PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.Results Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.Conclusions This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.Pathophysiology and treatment of rheumatic disease

Response to: 'Correspondence on 'EULAR definition of difficult-to-treat rheumatoid arthritis'' by Novella-Navarro et al

Pathophysiology and treatment of rheumatic disease

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

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