Infliximab dependency in children with Crohn's disease.
ABSTRACT Recently, infliximab dependency has been described.
To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000-2006 and to describe clinical and genetic predictors of long-term infliximab response.
A phenotype model of infliximab dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start)--complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse < or = 90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF-308 A>G, TNF-857 C>T, Casp9 93 C>T, FasL-844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed.
Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67-26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002).
Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype.
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ABSTRACT: A significant proportion of patients with initial response to Inflximab (IFX), subsequently lose response (LOR). Multicentre paediatric studies report LOR in 33% to 50% with 3-5year follow-up. Our retrospective study examined durability of response and predictors of LOR. From our IBD database of 185 children with CD, 65 received IFX maintenance therapy for luminal or fistulising Crohn's disease between January, 2006 and April, 2013. 47 with luminal CD ≥1year follow-up after commencing IFX were included. We evaluated variables associated with response and describe outcomes on those remaining on IFX at four time points; before IFX, after induction, at 1year and at the last follow-up. Response was divided into sustained primary, recovered, durable (combined sustained primary and recovered) and complete LOR (discontinuation from LOR or intolerance). Overall, 28/47 (60%) children sustained primary response over a median duration of 2.83years (1.6-4.4, IQR). 19/47 (40%) developed LOR (including 2 intolerant) at a median of 11months (9-19, IQR). Of 17 with LOR, 7 were successfully re-induced giving durable response (35/47, 74%); 6 failed dose intensification needing surgery (n=2), second anti-TNF (n=2) or both (n=2). 4 had surgery without dose intensification. LOR was associated with low BMI at diagnosis, lower height Z scores prior to induction, elevated CRP following induction (p=0.007) and failure to use concomitant IM (p=0.02). The cumulative probability of durable response to IFX in luminal CD was 83%, 74% and 70% after 1, 2, and 3years on IFX maintenance therapy.Journal of Crohn s and Colitis 01/2014; 8(8). DOI:10.1016/j.crohns.2013.12.017 · 3.56 Impact Factor
Gut 06/2014; 63(12). DOI:10.1136/gutjnl-2014-307126 · 13.32 Impact Factor
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ABSTRACT: Many physicians hesitate to recommend anti-tumor necrosis factor (TNF) therapy for pediatric patients with inflammatory bowel disease (IBD), due to concerns about risk of infection and cancer. We performed a systematic review to quantify the incidence of serious infection, lymphoma, and death among pediatric patients with IBD who received anti-TNF therapy. These values were compared with those expected from other treatments, from adults with IBD, and from the general pediatric population. We searched MEDLINE, EMBASE, Cochrane Collaboration, and Web of Knowledge for studies of infliximab therapy for children with ulcerative colitis or Crohn's disease, or adalimumab therapy for children with Crohn's disease. Standardized incidence ratios (SIR) were calculated, comparing rates of infection and cancer among pediatric patients exposed to anti-TNF agents vs expected rates from pediatric patients not exposed to anti-TNF therapies or adult patients exposed to anti-TNF agents. Our analysis included 5528 patients with 9516 patient-years of follow-up (PYF). The rate of serious infections among pediatric patients treated with anti-TNF agents (352/10,000 PYF) was similar to that of pediatric patients who received immunomodulator monotherapy (333/10,000 PYF; SIR 1.06; 95% confidence interval [CI], 0.83-1.36), but significantly lower than the expected rate for pediatric patients treated with steroids (730/10,000 PYF; SIR 0.48; 95% CI, 0.40-0.58) or adults treated with anti-TNF agents (654/10,000 PYF; SIR 0.54; 95% CI, 0.43-0.67). Five treatment-related deaths occurred (4 from sepsis and 1 from arrhythmia). Two patients developed lymphoma (2.1/10,000 PYF). This value is lower than the expected rate of lymphoid neoplasia in the entire pediatric population (5.8/100,000 PYF; SIR 3.5; 95% CI, 0.35 -19.6), in the population of pediatric patients receiving thiopurine monotherapy (4.5/10,000 PYF; SIR 0.47; 95% CI, 0.03-6.44), and among adults treated with anti-TNF agents (6.1/10,000 PYF; SIR 0.34; 95% CI, 0.04-1.51). Based on a systematic review, the risk of lymphoma is no greater among children with IBD who received anti-TNF therapy than those treated with other IBD therapies or adults treated with anti-TNF agents. The rate of serious infection is significantly lower among pediatric patients with IBD treated with anti-TNF agents than those treated with steroids, or adults with IBD who received anti-TNF therapy.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; DOI:10.1016/j.cgh.2014.01.021 · 6.53 Impact Factor