Title: Steroid Induction Regimen for Juvenile Idiopathic Arthritis (JIA)
Funder: Department of Health and Social Care

Abstract: Design: A UK-wide feasibility study Setting: NHS Trusts with Paediatric Rheumatology services Strategy for literature review: A review of recent literature, review of the latest revision of the European Medicines Agemcy (EMA) guideline on JIA trial design, review of the outcomes of the Single Hub Access for Rheumatology in Europe (SHARE) conclusions. Target populations: Patients <16 years with Juvenile Idiopathic Arthritis requiring Corticosteroid (CS) Treatment Health technologies assessed: The feasibility study will explore four CS delivery regimens (intra-articular corticosteroid injections (IACI), oral, intravenous (IV) pulsed, or depot intramuscular (IM) injections or a combination) for induction of treatment response and remission in patients with newly diagnosed or flaring JIA. The study will determine from HCP and PPI perspectives as well as from current practise, which modalities would be compared in a future RCT. Measurements of costs and outcomes 1 Costs: Determining specific health economic assessments will be left to the final RCT. 2 Outcomes: Informed by literature review and stakeholder engagement strategies outlined, the primary outcome is likely to be one of: assessment of active joint count; improvement in Juvenile Arthritis Disease Activity Score (JADAS) and assessment of function. PROMS & PREMS will be explored and definitions of remission identified by the Delphi and Consensus Meeting. Methods and Sample Size 1. National e-Survey: UK HCPs in both specialist children’s centres and DGHs with paediatric rheumatology clinics, identified through BSPAR, will be surveyed on current practice, reasons for treatment choices and capability/ acceptability of undertaking a trial, numbers of patients and type of JIA and CS use. 2. A qualitative study of patients and parents (identified by units) will probe acceptability of treatment routes, willingness to be randomised and provide consent, trial design and outcomes feeding into the Delphi and final study report. 3. Delphi Process: UK-wide HCPs with parents/ patients will be invited to participate in a 2 round Delphi process to achieve consensus on the primary outcome measure. 5. Consensus Meeting: (HCPs & parents/ patients) to finalise agreement on key aspects of proposed RCT including patient groups, primary outcome, control and treatment arms. 6. Prospective feasibility study including data on chosen primary outcome collected at 3 months to inform estimate of sample size for future RCT. 7. Report on feasibility of proposed RCT Project Timelines: The study will be completed in 21 months. Individual components: contracting, set-up and literature review – 6 months; surveys of practice 6 months; qualitative interviews 7 months; Delphi process and consensus meeting 10 months; prospective feasibility 10 months; final report for HTA 1 month. Individual components run in parallel. Expertise in the Team: The team has extensive multidisciplinary clinical expertise in developing and delivering clinical trials, extensive, highly relevant methodological experience in feasibility studies, literature reviews, qualitative studies, surveys of practice using mixed methods, consensus methods, core outcome set development, and PPI strategies. A Trial Steering Group will oversee all aspects of the feasibility study supported operationally by a Trial Management Group.

Lay abstract: What is JIA? JIA stands for Juvenile Idiopathic Arthritis. Arthritis means inflammation in the joints leading to pain, stiffness, swelling and warmth. It can cause damage and reduced movement in affected joints. The term JIA covers several types of arthritis that start under the age of 17 and for which there is no known cause. It is a chronic disease meaning that it can cause trouble for many years. Approximately half of young people will continue to suffer from arthritis as adults. Treatment: There are many good treatments for JIA including anti-inflammatory drugs, disease modifying drugs, and new ‘biologic’ drugs. They block the inflammation. Although these newer drugs are good, they are powerful and expensive and sometimes not effective enough. Patients often still need steroids at the start of treatment to induce remission of arthritis and if the arthritis flares up again. A short course of steroids can stop the flare and reduce increases in other treatments. There are four ways that steroids are given: by injection into joints (intra-articular), by injections through a drip into veins (intra-venous), by injections into the muscle (intramuscular depot) or by tablets taken by mouth (oral). These have all been used for decades but without comparative studies of the different routes. There is no agreement about the best way to give them and for how long. Steroids are used in many trials of new biologic drugs but so far there has been only one study directly comparing two different steroid preparations in joint injections. It is important to know how best to use steroids as they can have many side effects. They can cause weight gain, reduced growth, increased risk of diabetes, high blood pressure and weakened bones. It is important to work out the lowest dose and best way to give them for the shortest time. Study Aims: 1) To identify the best steroid treatments to compare in a future study (trial) and to decide on what outcome to measure 2) To see whether parents, patients and health care professionals (HCPs) would be willing and able to randomly allocate (like tossing a coin) patients to different steroid treatments 3) To find out if there are enough patients treated with steroids each year able to be included in a trial of steroids 4) To recommend if it is feasible to conduct a national head to head trial of comparing the effectiveness of steroids in JIA Methods 1) A thorough search of published research on steroids in JIA to identify important clinical outcomes. 2) A UK-wide study of practice to see what HCPs do currently 3) A national survey of HCPs to identify current treatments in different scenarios and what affects the decision to choose a specific treatment 4) Interviews with patients and parents to consider the design of a future trial comparing steroids and their delivery routes and to identify important outcomes as well as their thoughts on if they would take part in a trial 5) A consensus process: to gain agreement over the finer details of the study protocol where choices may differ and to decide which types of JIA should be included and to agree on what outcome measures will be used 6) A small study of the type of patients we think would be in a future trial receiving the proposed steroid treatments while observing any changes in the agreed outcome measures over a 3 month period so that we can calculate the numbers of patients that would be needed for a future trial. Finally, we will determine if the type of definitive trial that would help us to decide the best steroid approach to use for patients with JIA is actually possible to run.

Research activity codes: 6.1 PHARMACEUTICALS;7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFLAMMATORY AND IMMUNE SYSTEM