W1181 Long-Term Efficacy and Safety of Maintenance Infliximab for the Treatment of Moderate-to-Severe Pediatric Crohn's Disease: Results from the Reach Study

Abstract

Background: Infliximab, a chimeric anti-tumour necrosis factor alpha antibody, is now an established therapy for both Crohn disease (CD) and psoriasis. Among patients treated for CD, however, the paradoxical development of new-onset psoriasis has been reported in up to 15% of adult patients. We reviewed the prevalence of psoriasis developing in pediatric CD patients during infliximabmaintenance therapy, and examined the role of polymorphisms in the interleukin 23-receptor (IL-23R) gene, known to contribute to CD and psoriasis susceptibility. Methods: The medical records of all CD patients with documented skin abnormalities following the instigation of infliximab, at our center, were reviewed. DNA from patients developing psoriasis following infliximab was compared with that of diseasematched controls to examine the association of Il-23R polymorphisms with this paradoxical event. Results: 118 children received infliximab from January 2000 to August 2008. Thirteen children (11%), (9 males), developed new onset psoriasis following infliximab therapy. Persistent luminal disease despite conventional therapy (n=10) and perianal disease (n=3) were the indications for initiation of infliximab. The median duration of infliximab exposure at the time of psoriasis onset was 1.0 year (IQR 0.6 2.1). The median age at diagnosis of psoriasis or psoriasiform lesions was 14.7 years (IQR 14.2 15.2). 11 of 13 responded well to topical steroid therapy. 2 patients discontinued infliximab, both with resolution of their psoriasis. DNA was available on 8 of the 13 patients who developed psoriasis, 137 diseasematched controls and 86 ulcerative colitis (UC) patients. 75% of cases were homozygous for the Il-23R rs10489629 single nucleotide polymorphism (SNP) compared with 42% of CD controls and 28% of UC controls, with an allele frequency of 88%, 65% and 53% for cases, CD controls and UC controls respectively. The odds ratio for an infliximab-exposed patient developing psoriasis was 3.8 for heterozygotes and 14 for homozygotes (p=0.07). Conclusion: The frequency of new-onset psoriasis in this pediatric cohort of CD patients treated with infliximab mirrors that reported in adult series. Most patients respond well to topical therapy and in the majority of cases, anti-TNF therapy can be continued. We found a trend towards association of this adverse event with a variation in the Il-23R gene. However, the true significance of this variation warrants further investigation in large, adequately powered, studies.