FRI0074 UNDERLYING PROBLEMS AND IMPACT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A CROSS-SECTIONAL CASE-CONTROL STUDY
Authors: N. M. T. Roodenrijs, M. C. Van der Goes, P. Welsing, J. Tekstra, F. Lafeber, J. W. G. Jacobs, J. M. Van Laar
Journal: Annals of the Rheumatic Diseases (2020)

Background: Difficult-to-treat (D2T) RA is defined here by signs and symptoms, suggestive of active/progressive RA, which are perceived as problematic by rheumatologist and/or patient, and are present despite treatment according to EULAR recommendations including ≥2 b/tsDMARDs with different mechanisms of action. 1 Its treatment is generally based on trial-and-error and challenged by several underlying problems (Figure 1), 2-4 of which the exact impact is unknown. Objectives: To obtain insight into the potential problems underlying D2T RA and into its impact. Methods: Consecutive RA patients fulfilling the 2010 ACR/EULAR classification criteria, treated according to current standard of care for ≥1 year, are being enrolled, and categorised as D2T or not (controls). Potential problems underlying D2T RA (Figure 1) and its impact on quality of life and physical functioning were assessed and compared between the two patient groups. Results: In this preliminary analysis, 45 patients are classified as having D2T RA and 100 are controls (Table 1). Fibromyalgia (33 vs 9%), depression (18 vs 4%), a mismatch between patient and rheumatologist in wish to adapt treatment (51 vs 15%) and DMARD discontinuation because of adverse events (96 vs 57%), were statistically significantly more frequent in D2T RA patients than in controls. Higher levels of threatening illness perception and helplessness, and more comorbidities according to EULAR domains were found in D2T RA patients (Figure 2). Other potential problems did not differ statistically significantly. Table 1. Patient characteristics D2T RA (n=45 ) Control RA (n=100 ) p-value Demographics Age ‡ 60.9 (10.8) 64.5 (10.9) 0.06 1 Female, % 76 72 0.66 2 Disease characteristics Disease duration, years 17.0 (10.0-27.5) 14.0 (8.0-24.0) 0.18 3 RF positivity, % 76 65 0.21 2 ACPA positivity, % 71 65 0.47 2 DAS28-ESR 4.0 (3.4-5.7) 2.5 (1.8-3.3) &lt;0.001 3 Drugs Number of previous DMARDs 7 (5-10) 2 (1-4) &lt;0.001 3 Number of current DMARDs 2 (1-2) 1 (1-2) 0.03 3 Current conventional synthetic DMARDs, % 74 86 0.07 2 Current biological DMARDs, % 57 39 0.06 2 Current targeted synthetic DMARDs, % 22 0 &lt;0.001 2 Glucocorticoid therapy, % 53 16 &lt;0.001 2 Dose, mg/day prednisone or equivalent daily, in users 7.5 (5.0-13.8) 5.0 (5.0-7.5) 0.03 3 ACPA: anti-citrullinated protein antibodies; D2T: difficult-to-treat; DAS28-ESR: disease activity score assessing 28 joints using erythrocyte sedimentation rate; DMARD: disease-modifying antirheumatic drug; mg: milligram; n: number; RF: rheumatoid factor. Numbers are median (interquartile range), unless stated otherwise; ‡ mean (standard deviation). Differences between groups were analysed using: 1. Independent T-test; 2. Chi-square Test; 3. Mann-Whitney U Test. Quality of life and physical functioning were significantly lower in D2T RA patients than in controls (median (IQR) EQ-5D 2.6 (1.8-3.0) vs 1.6 (1.4-2.2) and HAQ 1.8 (1.3-2.1) vs 1.0 (0.5-1.4), p&lt;0.001). Conclusion: This first prospective study describing a cohort of D2T RA patients shows higher occurrences of potential underlying problems and a higher clinical impact. These should be recognised in daily practice and taken into account before considering another DMARD switch. More detailed research on disease state (biomarkers, radiographic damage) and use of medication (drug levels and in-depth interviews on treatment non-adherence) will follow. References: [1]Smolen JS et al. Ann Rheum Dis 2020. Epub ahead of print. [2]Buch MH. Ann Rheum Dis 2018; 77 :966–9. [3]de Hair MJH et al. Rheumatology 2017; 57 :1135–44. [4]Roodenrijs NMT et al. Ann Rheum Dis 2018; 77 :1705–9. Disclosure of Interests: Nadia M. T. Roodenrijs: None declared, Marlies C. van der Goes: None declared, Paco Welsing: None declared, Janneke Tekstra: None declared, Floris Lafeber Shareholder of: Co-founder and shareholder of ArthroSave BV, Johannes W. G. Jacobs Grant/research support from: Roche, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS