Op0134 real World “Poly-Refractory Ra”: A Rare but Unmet Clinical Challenge

Abstract

BackgroundIn an age of dose optimization and drug tapering due to excellent conventional (c), biological (b) or targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs), the fact remains that many patients still have active disease, being therapy refractory, sometimes to multiple DMARDs. In 2021, EULAR defined the term “Difficult-to-treat (D2T) Rheumatoid Arthritis” as failure of two or more different classes of b/tsDMARDs post csDMARDs (1) but the rate of failure to all available DMARD classes in the real-world setting (poly-refractory RA) is not established. Moreover, the DAS-28-CRP score can be elevated in patients with either persistent inflammatory RA (PIRRA) or non-inflammatory RA (NIRRA), where the latter do not benefit from medication change [2]. PIRRA patients have at least one clinically swollen joint, with objective evidence of active inflammation in power Doppler ultrasound (PDUS), often with elevated CRP levels, whilst NIRRA patients have apparent clinical swelling but absence of PDUS and often normal CRP levels.ObjectivesThis study determined the prevalence of EULAR-defined refractory RA (D2T RA) in Leeds. Secondly, we established the prevalence of poly-refractory RA, i.e., patients that failed all available b/tsDMARD classes. Finally, we determined NIRRA/PIRRA phenotypes in refractory disease.Methods1591 RA patients receiving b/ts DMARDs therapy between 2018-2022 were identified as part of a service evaluation, excluding those where DAS-28-CRP was unavailable. Patients fulfilling EULAR-ACR criteria for D2T RA, with DAS-28-CRP≥ 3.2 and US imaging where available were evaluated. Patients were further divided into NIRRA and PIRRA, according to the presence/absence of signs of active synovitis as indicated by PDUS (Figure 1).Results242/1591 (15.2%) met the EULAR D2T criteria of failing at least 2 b/tsDMARDs. 89/1591 (5.6%) failed 2 classes only, with a mean disease duration (mDD) of 11 years. 60/1591 (3.8%) failed 3 classes (mDD= 18) and 52/1591 (3.3%), 4 classes (mDD= 10.5). However, just 41/1591 (2.5%) had poly-refractory RA having failed all 5 classes (mDD= 21). Of them, 37/41 (90%) failed multiple drugs within each class. 4/41 (10%) poly-refractory and 45/242 (18.5%) of all EULAR D2T cases were seronegative. Regarding joint involvement patterns, most had typical small joint RA disease pattern but 26/242 (11%) had a predominant large joint pattern. 18/41 (43%) of the poly-refractory RA group had CRP levels within the normal ranges despite a DAS-28-CRP score above 3.2 (mean DAS-28-CRP of 5.3). 71 D2T RA patients had recent US of clinically involved joints, including 28 poly-refractory RA cases. 18/28 (64%) poly-refractory were considered PIRRA as evidenced by synovial hypertrophy and PDUS positivity in at least one evaluated clinically swollen joint. 32/71 (45%) D2T RA had no signs of active synovitis in PDUS being considered NIRRA. Of them, 17/32 (53%) had no synovial thickening in US in suspected clinically involved joints. Specifically in the poly-refractory group, the CRP levels were within normal ranges in 6/10 (60%) NIRRA patients, while just 7/18 (39%) PIRRA cases had normal CRP levels.ConclusionAlthough 15.2% of Leeds RA patients met the EULAR criteria for D2T RA, real world poly-refractory RA was present in only 2.5%. Almost half of these patients had no PDUS changes on US and/or had normal CRP levels. These findings highlight a twofold clinical challenge in refractory RA with half of this group (both D2T and poly-refractory RA) having true inflammation that may need new mechanisms of action, but the other half would not be likely to benefit from new DMARD treatment strategies.References[1] Nagy G, Roodenrijs NM, Welsing PM et al. Ann Rheum Dis. 2021 Jan;80(1):31–5.[2] Buch MH, Eyre S, McGonagle D. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021 Jan;17(1):17–33.Figure 1.Flow-chart showing the prevalence of poly-refractory, PIRRA and NIRRA patients among Leeds RA patients.Acknowledgements:NIL.Disclosure of InterestsNone Declared.