PSAP 2010/2011 Hot topics in Paediatrics Question of the month June 2011

Paed - Rheumatology
Paed - General; Pharmacology and Therapeutics

Tom is a 10 year-old boy with systemic onset Juvenile Idiopathic Arthritis (JIA) diagnosed 12 months ago. He has been treated with weekly oral methotrexate (MTX) and intermittent intra-articular steroids. Because of his symptoms, he has also received daily oral steroids for several months. He now has significant Cushingoid facies and has a height velocity below the third percentile for age.

References

Beresford MW, Baildam EM. New advances in the management of juvenile idiopathic arthritis - 1: non-biological therapy. Arch Dis Child Educ Pract Ed. 2009; 94:144-150. Beresford MW, Baildam EM. New advances in the management of juvenile idiopathic arthritis - 2: the era of biologicals. Arch Dis Child Educ Pract Ed. 2009; 94:151-156. http://www.bspar.org.uk/downloads/clinical_guidelines/BSPAR_METHR.pdf - BSPAR Executive Committee. British Society for Paediatric and Adolescent Rheumatology guidelines on methotrexate use in paediatric rheumatology. 2005. Available at: http://www.bspar.org.uk/downloads/clinical_guidelines/BSPAR_METHR.pdf Accessed: 5/11/2009.

Regarding therapy for JIA:

You have answered this question. Please go to the next question. Daily oral corticosteroid treatment in this condition has no current role. Almost of children with JIA will respond to methotrexate at standard doses. Major gastro-intestinal side effects occur in approximately 40% of children with JIA who are treated with methotrexate. Etanercept has been demonstrated to cause a significant reduction in disease flare in children with polyarticular JIA. Subcutaneous infliximab is a useful alternative treatment modality

Critique
JIA is defined as arthritis where identifiable causes have been excluded beginning before the childs 17th birthday and persisting for at least 6 weeks. Early aggressive interventions are now emphasised, and there is general support for MTX as the first line disease modifying anti-rheumatic drug (DMARD) in JIA. Maintenance doses of 10-15 mg/m2/week are often used. At these standard doses, gastrointestinal side effects (nausea, vomiting and anorexia) occur in approximately 12% of patients. Of more concern, elevations of liver transaminases and haematological disturbances can occur and are the basis for monitoring regimens (see The British Society for Paediatric and Adolescent Rheumatology Clinical Guidelines). The response rate in JIA to standard MTX treatment doses is approximately 72%. Long-term oral corticosteroid use has declined markedly in JIA, because of the significant side effects (particularly in relation to bone health and growth). However, two British rheumatologists, Beresford and Baildam, in a recent review article stated indications for their ongoing use to include severe systemic features associated with systemic-onset JIA, for induction of remission in early aggressive treatment of polyarticular disease or as a bridging medication until other treatments become effective. Increasingly, children who fail to respond to conventional DMARD therapy have received treatment with biological therapy. The first multi-centre, double blind randomised controlled trial of biological therapy in JIA involved use of subcutaneous etanercept (ETN, a tumour necrosis factor blocker) in children aged 6 to 17 years with polyarticular JIA. In that study, 28% of the patients receiving ETN compared to 81% of the children receiving placebo had a disease flare over a 4 month period. Within the Dutch National Register, a study group of 146 JIA patients were analysed. In that group 77% of patients had demonstrable improvement in the first 3 months of treatment. Whilst concerns have been

raised about the long-term safety profile of biological treatments, a low serious adverse event rate (0.029 per patient year for ETN-treated patients) has so far been reported. Whilst ETN is administered subcutaneously, Infliximab (a monoclonal antibody against TNF alpha) is administered intravenously, initially at weeks 0, 2, 4 and then 8-weekly. One study, which looked at children with JIA with polyarthritis treated for 3 months, failed to show a significant improvement in those treated with infliximab when compared to placebo (although there was a trend towards improvement of symptoms).