Pediatric Rheumatology Online Journal → August 2003 → Newer Treatments → Anti-Tumor Necrosis Factor Therapy → Abstract #161

SEVERE AUTOIMMUNE DISEASE IN SIBLINGS OF A SOMALIAN FAMILY AND RESPONSE TO TREATMENT WITH INFLIXIMAB

N. M. R. Wilkinson,¹ P. A. Livermore,¹ P. Woo.¹

¹Paediatric Rheumatology, Great Ormond Street Hospital, London, United Kingdom

We describe the use of infliximab in three siblings of a consanguinous Somalian family with an extensive family history of polyarthritis, inflammatory bowel disease (IBD), autoimmune hepatitis and inflammatory eye disease spanning four generations and resistant to conventional DMARD's. The three sibs have HLA class II antigens associated with JIA (HLA, DRB1* 08,13) and also have, together with two other sibs, HLA-DRB1*03, considered protective for IBD. Infliximab has been shown to be effective for both IBD and polyarthritis in adults and children.
Infliximab, initial dose 3mg/kg on weeks 0, 2, 6, 14, and 22, and methotrexate at 20mg/m, was given to three females aged 5-17 years, each of whom have polyarthritis and growth failure. Each patient had experienced persistent disease activity mirrored by high ESR and 1-3 monthly polyarthritic flares associated with pain, swelling, contractures and reduced function. Two have macroscopic evidence of enteropathy, yet have non-specific inflammation on biopsy. Elemental feeds and topical therapies were unsuccessful, as was methotrexate for 2.5-7 years, in combination with sulphasalazine and oral, intravenous and intraarticular steroids as appropriate.
All three were resistant to treatment, despite increasing the dose and frequency of infliximab to 6mg/kg and six weekly infusions. Each flared on at least 3 occasions requiring intraarticular steroids. There was little change in active joint count, physician's global assessment and ESR, although ESR fell initially to normal in one sib associated with improved haemoglobin concentration. Anaemia persisted in the others. Temporary infusion reactions were observed in 2 siblings at low dose, but not high dose, and included transient bradycardia, hypotension and hypothermia. Subsequent to an increase in dose, one sib developed septic arthritis. Another experienced an uncomplicated course of chicken pox.
Analysis of inherent TNF production may explain the poor response to infliximab and alternative combination therapy are being reconsidered.