P131 Defining refractory disease in RA and polyarticular JIA: a systematic review
Authors: Chaplin Hema , Carpenter Lewis , Raz Anni , Nikiphorou Elena , Lempp Heidi , Norton Sam 
Published: April 2021

Abstract
Background/Aims
A systematic approach to define patients with rheumatoid arthritis (RA) or polyarticular juvenile idiopathic arthritis (PolyJIA) who do not adequately respond to treatment and experience persistent symptoms (refractory disease) is absent. The objective of the systematic review was to identify how refractory disease (or relevant terminology variations) in RA/PolyJIA is defined and establish the key components/constructs of such definitions.
Methods
Searches were undertaken of English language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/PolyJIA, with clear components to the description (e.g. disease activity assessment specified, patient perspective, number of drugs to classify non-response). A narrative synthesis mapping of the definitions was undertaken to describe refractory disease in RA/PolyJIA and classify each component within each definition through a qualitative content analysis.
Results
Of 6,251 studies screened, 646 studies met the inclusion criteria; 581 reported non-response criteria and 65 reported refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasising persistent disease activity and symptoms, despite treatment with at least one bDMARD. Of the papers with clear definitions for Refractory disease, 41 components were identified and categorised into three key themes: Resistance to multiple drugs/regimes with different mechanisms of action: descriptions of drugs/regimes failed, not tolerated, discontinued/switched, by specifying name, number or class of drugs failed (range 1-8 but typically ≥2 bDMARDs) and duration of treatment, and steroid use/dependency.Persistency of physical symptoms and disease activity: range of various disease activity criteria (including not achieving remission), descriptions of other patient-reported outcomes or symptoms e.g. patient global or pain VAS, presence or absence of inflammation, disease severity including new joint activity, damage or replacements.Other contributing factors: biomechanical or degenerative drivers, adverse event, co-morbidities or extra-articular manifestations, serology (RF Status) or anti-bodies (anti-CCP) and incorrect diagnosis or not relevant treatment.
The most common labels were “Refractory” (80%), of which 32.7% used the term “Refractory RA” and 13.5% stating “Refractory to (drug name/class)”. “Difficult-to-treat RA” (23.1%) and “Treatment Resistant RA” (15.4%) were the most popular from remaining terms (20%). Only the minority (16.9%) reported explicitly how their definition was generated e.g. clinical experience or statistical methods.
Conclusion
Refractory disease can be defined as resistance to multiple drugs/regimes with different mechanisms of action as evidenced by persistency of physical symptoms and high disease activity, including contributing factors. There is a need for a clear unifying definition as the plethora of different definitions makes both study comparisons and appropriate identification of patients difficult.
Disclosure
H. Chaplin: None. L. Carpenter: None. A. Raz: None. E. Nikiphorou: None. H. Lempp: None. S. Norton: None.