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.
Conference Paper: A 109.5mW 1.2V 600M texels/s 3-D graphics engine[Show abstract] [Hide abstract]
ABSTRACT: A 3D graphics engine consists of a programmable floating-point geometry engine and a rasterization engine to adapt to various memory-based set associative cache mechanism. The IC achieves 4.7M vertex/s and 600M texel /s systems, the rasterization engine has a coordinate I and dissipates 109.5mW. A 0.18 μm 5M CMOS process is used to implement the 25.4mm<sup>2</sup> IC operating at 1.2V.Solid-State Circuits Conference, 2004. Digest of Technical Papers. ISSCC. 2004 IEEE International; 03/2004
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ABSTRACT: Infliximab dependency in children with Crohn's disease (CD) has recently been described and found to be associated with a decreased surgery rate. To assess infliximab dependency of adult CD patients, evaluate the impact on surgery, and search for possible clinical and genetic predictors. Two hundred and forty-five CD patients treated with infliximab were included from Danish and Czech Crohn Colitis Database (1999-2006). Infliximab response was assessed as immediate outcome, 1 month after infliximab start: complete, partial, and no response. Three months outcome, after last intended infusion: prolonged response (maintenance of complete/partial response), infliximab dependency (relapse requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response). Forty-seven percent obtained prolonged response, 29% were infliximab dependent and 24% nonresponders. The cumulative probability of surgery 40 months after infliximab start was 20% in prolonged responders, 23% in infliximab-dependent patients and 76% in nonresponders (P<0.001). The cumulative probability of surgery at 40 months in patients on maintenance versus on demand regime was 33 and 31%, respectively (P=0.63). No relevant clinical or genetic predictors were identified. The infliximab dependency response seems to be equivalent to the prolonged response in adult CD patients when comparing surgery rates.European journal of gastroenterology & hepatology 10/2010; 22(10):1196-203. DOI:10.1097/MEG.0b013e32833dde2e · 2.15 Impact Factor
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ABSTRACT: The role of 5-aminosalicylic acid (5-ASA) in Crohn's disease is unclear. The outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency was retrospectively assessed in consecutive cohort of 537 Crohn's disease patients diagnosed 1953-2007. Following outcome definitions were used: Immediate outcome (30 days after 5-ASA start) defined as complete/partial response (total regression/improvement of symptoms) and no response (no regression of symptoms with a need of corticosteroids, immunomodulator or surgery). Long-term outcome defined as prolonged response (still in complete/partial response 1 year after induction of response); 5-ASA dependency (relapse on stable/reduced dose of 5-ASA requiring dose escalation to regain response or relapse ≤1 year after 5-ASA cessation regaining response after 5-ASA re-introduction). One hundred sixty-five (31%) patients had monotherapy with 5-ASA. In 50% 5-ASA monotherapy was initiated ≤1 year after diagnosis (range 0-49 years). Complete/partial response was obtained in 75% and no response in 25% of patients. Thirty-six percent had prolonged response, 23% developed 5-ASA dependency and 38% were non-responders in long-term outcome. Female gender had higher probability to develop prolonged response or 5-ASA dependency (OR 2.89, 95%CI: 1.08-7.75, p=0.04). The median duration (range) of 5-ASA monotherapy was 34 months (1-304) in prolonged responders, 63 (6-336) in 5-ASA dependent and 2 (0-10) in non-responders. A selected phenotype of Crohn's disease patients may profit from 5-ASA. Fifty-nine percent of patients obtained long-term benefit with 23% becoming 5-ASA dependent. Prospective studies are warranted to assess the role of 5-ASA in Crohn's disease.Journal of Crohn s and Colitis 11/2010; 4(5):575-81. DOI:10.1016/j.crohns.2010.06.002 · 3.56 Impact Factor