Steroid TreAtment tRial in JIA: A randomised trial to compare effectiveness, safety and cost-effectiveness of intravenous versus oral corticosteroid induction regimens for children and young people with juvenile idiopathic arthritis. (STAR-JIA)

Research summary

Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease affecting 1 in 1000 children with around 12,000 children with JIA in England and Wales [1,2]. Delay in diagnosis and under-treatment lead to joint damage,disability and reduced quality of life [3]. In the UK and most of the world,children and young people with new-onset poly-articular Juvenile Idiopathic Arthritis (pcJIA) are commenced on corticosteroids and methotrexate [2,4,5]. As methotrexate can take several months to have an effect,corticosteroids are used to rapidly control inflammation with aims of reducing symptoms such as pain,stiffness,improving function and reducing damage [6]. Limited evidence informs optimal route or dose of corticosteroids in this group and practice varies hugely including administration via intravenous (IV),oral,intra-articular (IA) and intra-muscular (IM) routes [4,5,7]. The UK paediatric rheumatology clinical community and consumer representatives have strongly stated that further work should be conducted in this area to determine the most effective induction treatment to inform clinical practice. This question formed the basis of a NIHR HTA funded feasibility study SIRJIA (Steroid Induction Regimen for Juvenile Idiopathic Arthritis),which showed that a definitive randomised controlled trial is feasible and needed. A literature review formed part of this feasibility report [7]. Using the same search terms,an updated search up until June 2021 did not identify any new controlled studies of corticosteroids use in pcJIA. A search of clinicaltrials.gov in June 2021 identified no ongoing trials. Several consensus treatment plans were identified highlighting clinician equipoise and lack of evidence to support oral versus intravenous corticosteroids in this group [4,5]. Whilst comparison of multiple routes of corticosteroids are possible,we have chosen comparison of oral and intravenous corticosteroids when prescribed in combination with the non-interventional medicinal product,methotrexate,because there is more pressing urgency for evidence of their efficacy,safety and cost-effectiveness than intra-articular or intramuscular in pcJIA. Specifically: i) The feasibility study literature review (and our updated review 2021) shows ongoing lack of evidence for intravenous and oral corticosteroids but evidence to support use of intra-articular corticosteroids; ii) There is a considerable delay from decision to treat with intra-articular corticosteroids (often requiring general anaesthetic (GA) in children and young people) to administration (unpublished data from co-applicants) leading clinicians to use additional oral or intravenous corticosteroids whilst awaiting theatre. Limited availability to timely theatre and potential randomisation to GA were identified as a source of risk in the intra-articular corticosteroid arm in SIRJIA; [7] iii) Intramuscular administration of corticosteroids is uncommon and so less benefit will be gained from its inclusion in this study; iv) Cost and impact on families is disproportionate between IV and oral (estimated cost IV £1400 vs £7 for oral and requires 3 days missed school/work,cannulation). Understanding the efficacy,safety and cost-effectiveness of oral corticosteroids versus IV corticosteroids will have the highest impact for the NHS and patients/families,as choices between these drugs are currently opinion and anecdotal rhetoric-based rather than evidence-based.

Principal Investigator

Dr Kathryn Bailey

Contact us

Email: childrensresearch@ouh.nhs.uk

IRAS number

1007610