Refractory Inflammatory Arthritis definition and model generated through patient and multi-disciplinary professional modified Delphi process
Authors: Chaplin Hema , Bosworth Ailsa , Simpson Carol , Wilkins Kate , Meehan Jessica , Nikiphorou Elena , Morris Rona Moss- , Lempp Heidi , Norton Sam 
Published: September 2022

ABSTRACTObjectiveVarious definitions have been proposed for Refractory Disease in people with Rheumatoid Arthritis; however, none were generated for Polyarticular Juvenile Idiopathic Arthritis or involving adult and paediatric multidisciplinary healthcare professionals and patients. The study aim is to redefine Refractory Disease, using Delphi methodology.MethodsThree rounds of surveys (one nominal group and two online (2019–2020)) to achieve consensus using a predetermined cut-off were conducted voting on: a) name, b) treatment and inflammation, c) symptoms and impact domains, and d) rating of individual components within domains. Theoretical application of the definition was conducted through a scoping exercise.ResultsVotes were collected across three rounds from Patients, Researchers and nine multi-disciplinary healthcare professional groups (n=106). Refractory Inflammatory Arthritis was the most popular name. Regarding treatment and inflammation, these were voted to be kept broad rather than specifying numbers/cut offs. From 10 domains identified to capture symptoms and disease impact, six domains reached consensus for inclusion: 1) Disease Activity, 2) Joint Involvement, 3) Pain, 4) Fatigue, 5) Functioning and Quality of Life, and 6) Disease-Modifying Anti-Rheumatic Drug Experiences. Within these domains, 18 components, from an initial pool (n=73), were identified as related and important to capture multi-faceted presentation of Refractory Inflammatory Arthritis, specifically in Rheumatoid Arthritis and Polyarticular Juvenile Idiopathic Arthritis. Feasibility of the revised definition was established (2022-2023) with good utility as was applied to 82% of datasets (n=61) incorporating 20 outcome measures, with two further measures added to increase its utility and coverage of Pain and Fatigue.ConclusionRefractory Inflammatory Arthritis has been found to be broader than not achieving low disease activity, with wider biopsychosocial components and factors incorporating Persistent Inflammation or Symptoms identified as important. This definition needs further refinement to assess utility as a classification tool to identify patients with unmet needs.What is already known on this topicIn recent years within Rheumatology, parallel bodies of work have reached similar conclusions regarding the broadening of the Refractory or the wider Difficult-to-Treat concept.What this study addsIn this paper, we provide a different angle to define, measure, and conceptualise Refractory Inflammatory Arthritis, using health psychology theory across Polyarticular Juvenile Idiopathic Arthritis and Rheumatoid Arthritis with the input of patients, rheumatologists, and multi-disciplinary healthcare professionals.We support and extend recent definitions of refractory rheumatoid arthritis by detailing a three-part definition identified as important to both patients and multi disciplinary healthcare professionals that can also be applied to Polyarticular Juvenile Idiopathic Arthritis: 1) Treatment, 2) Inflammation, and 3) Symptoms and Impact with 18 specific components within 6 domains. The Refractory Inflammatory Arthritis definition can be operationalised as a classification tool using 22 routinely collected data points to identify those who need further targeted support and treatment.We have applied a biopsychosocial formulation model for Refractory Inflammatory Arthritis covering perpetuating and protective factors to guide management strategies and present wider contextual factors involved in the experience of Refractory Inflammatory Arthritis.How this study might affect research, practice or policyThe development of the Refractory Inflammatory Arthritis definition presented here included consideration of content and discriminant validity indicators to provide a clinical and research tool to appropriately classify and measure Refractory Inflammatory Arthritis with alignment to routinely used measures.