Strategies towards personalised medicine in Juvenile Idiopathic Arthritis; the MyJIA project

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease that may cause damage and disability in childhood. New drugs and treatment strategies, notably tumour necrosis factor (TNF)-inhibitors have ameliorated symptoms in JIA, although the majority of them do not reach a state of no disease activity. Injection of glucocorticoid into joints are widely used, but the procedure is painful and on children usually done in general sedation. No controlled studies have assessed the efficacy of joint injections, and we do not know if they are beneficial in JIA patients starting with TNF-inhibitors. The MyJIA trial is a national randomised clinical trial designed to assess if using joint injections in combination with TNF-inhibitors are superior to TNF-inhibitor alone. All health regions are involved and Oslo University Hospital manages the trial. The main aimed-for outcome is sustained remission, which means no sign or symptoms of active disease after 6 and 9 months. 200 children will be included and followed up with modern treatment strategies for one year. Patient and parents reported outcome measures are recorded. All patients undergo clinical and ultrasound examinations; some also MRI. Blood samples are taken for immunogenetic and drug-monitoring analyses. Through exploration of the extensive data collections, the MyJIA trial will contribute to the development of personalised treatment strategies for JIA patients. The study has two possible outcomes that will both be of importance and impact clinical practice. If the strategy including joint injections appear superior, MyJIA will enhance the evidencebased treatment recommendations with more emphasis on joint injections. If joint injections are redundant, the substantial costs and time associated with the injections will be reduced, as well as the discomfort, side effects and risks for the patients. The results, regardless of the outcome, will alter, individualise and improve treatment recommendations for JIA. So far, 165 patients have been included from the University Hospitals in Oslo, Northern Norway, Bergen, and Stavanger. Further inclusion is ongoing. The participants are assessed at baseline, after 6 weeks and after 3, 6, 9 and 12 months. We have evaluated a scoring system for ultrasound findings in children with arthritis.

Inhibitors of TNFa reduce inflammation in JIA patients, but only 20-40 percent achieve a state of no or very little disease activity. Tailored glucocorticoid joint injections are widely used (usually in general anaesthesia), but no controlled studies have addressed the effect of this approach. In Norway there are unique possibilities for early interventions, rapid escalation of medication and individualized therapy. We aim to find the optimal ways to increase disease control and improve quality of life for JIA patients. Our hypothesis is that in JIA patients starting TNF-inhibitors, added steroid injection of inflamed joints, will lead to improved outcomes compared to TNF-inhibitors with no joint injections, and that therapeutic drug monitoring, modern imaging and biologic and clinical profiling can be utilised to characterise JIA patients with different anti-TNF responses. MyJIA is a national investigator initiated 12 month RCT of JIA patients starting TNF-inhibitors; 186 JIA patients will be randomised at baseline to A) concomitant intra-articular glucocorticoid injections versus B) no injections. Primary endpoint is the rate of sustained remission from 6 to 12 months. Possible risk factors for not reaching remission will be analysed including clinical characteristics, drug antibodies/serum concentrations, patients’ reported health status and preferences, molecular signalling (based on transcriptional, cellular and genetic risk) and synovitis detected by modern imaging (ultrasound and whole-body MRI). Patients will be recruited from all health regions through an established collaboration. Unit of Pediatric Rheumatology, OUH, with an extensive research track in this field, will be the coordinating centre. Broad research cooperation across disciplines is established. The trial is highly innovative in evaluating treatment options and strategies to individualise and optimise the efficacy and safety of JIA treatment