Tailoring Treatment in Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children occurring in about 16-150/100,000/year and an important cause of short-term and long-term disability.

The current therapeutic strategies in JIA are time-consuming, physician-centered and nontransparent. For drug choices in 2011 the worldwide very much appreciated “ACR clinical practice guidelines (CPG) recommendations on the treatment of JIA” were published. The ACR-CPG is followed in less than 1/3 of all our cases and its implementation would make us treat around 60% more polyarticular JIA (PJIA) patients at 3 and 6 months with anti-tumour necrosis factor biologicals (anti-TNF). However, our physician’s decision not to escalate was correct in around 75% that stayed on MTX, thus the ACR-CPG seems to result in over-treatment with anti-TNF.

The use of (c)JADAS in identifying patients in need of anti-TNF therapy outperformed the ACR-CPG with much higher sensitivity, specificity and accuracy. The performance of the JADAS overall did not improve by adding the ESR and improved when the patient VAS contribution to the total score was increased to its normal 1/3. We are confident that treat-to-target by regular assessment of cJADAS and adapting therapy accordingly will greatly improve JIA care, even with the same step-up sequence of drugs.

In 2011 we set up an international pharmacovigilance database for JIA patients called Pharmachild. It now contains data from 32 countries, 86 centers and 9,000 JIA patients. Only 9.9% had at least one moderate infection during a median follow-up of 5.3 years. MTX-use increased the infection rate by 5.1, which was lower combined with a biologic (OR 3.7) and even lower for a biologic only (OR 2.7). The addition of steroids to both MTX and biologics however increased the risk of infections more significantly (OR 11.9 and 10.5, respectively). A huge increase in the risk (OR 112) for infection associated with rituximab with steroids and DMARDs within 6 months was found.

The opportunistic infection (OI) list we produced can be used as reference for future works in order to identify OI in immune-suppressed children. In Pharmachild 17.4% of severe, very severe or serious infections were opportunistic; the most frequent opportunistic pathogens were herpes viruses (excluding primary varicella) and mycobacterial infections.

In Pharmachild 4,451 comorbidities in 3,059 (37%) of the 8,309 patients were found. Uveitis, psoriasis and macrophage activation syndrome forming the top 3. Surprisingly clinical thyroid disease ranked as number 5. Celiac disease, diabetes mellitus and inflammatory bowel disease were reported in 1/200 patients each. Malignancies were rare events with a prospective incidence rate of 3.6 per 10,000 patient-years comparable to the 4.3 per 10,000 patient-years in a normal childhood population. Having a comorbid condition negatively impacted our patients on pain, well-being, functioning and quality of life.

A pilot-study in 6 very therapy refractory JIA patients showed that mesenchymal stromal cells infusions are safe, although one should be aware of (evolving) macrophage activation syndrome in systemic JIA patients and consider to not concomitantly discontinue the “failing” biologic treatment. There was also a hint for effectiveness in 4/6 patients.