Publications (65) View all
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Article: Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children.
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ABSTRACT: The IMAgINE 1 study (NCT00409682) evaluated the safety and efficacy of adalimumab double-blind maintenance dosing regimens following open-label induction for pediatric patients with moderate to severe Crohn's disease (CD). We studied 192 patients with Pediatric Crohn's Disease Activity Index (PCDAI) scores >30 for whom conventional treatment was unsuccessful. Patients received open-label induction therapy with subcutaneous adalimumab at weeks 0 and 2 (160 mg and 80 mg, or 80 mg and 40 mg, for body weight ≥40 kg or <40 kg). At week 4, 188 patients were assigned to groups based on achievement of clinical response (defined as decrease in PCDAI ≥15 points from baseline; 155/188 [82.4%]) and prior exposure to infliximab (82/188 [43.6%]). Groups were given double-blind maintenance therapy with adalimumab at high (40 mg or 20 mg for body weight ≥40 kg or <40 kg; n = 93) or low doses (20 mg or 10 mg for body weight ≥40 kg or <40 kg; n = 95) every other week for 48 weeks. Clinical remission (PCDAI ≤10) at week 26 (the primary end point) was compared between groups using the Cochran-Mantel-Haenszel test, adjusting for strata, with nonresponder imputation. Adverse events were monitored to evaluate safety. A total of 152 of 188 patients (80.9%) completed all 26 weeks of the study. At week 26, 63 patients (33.5%) were in clinical remission, with no significant difference between high- and low-dose groups (36/93 [38.7%] vs 27/95 [28.4%]; P = .075). No new safety signals were detected. Adalimumab induced and maintained clinical remission of children with CD, with a safety profile comparable to that of adult patients with CD. More children who received high compared with low dose were in remission at week 26, but the difference between dose groups was not statistically significant.Gastroenterology 05/2012; 143(2):365-74.e2. · 11.68 Impact Factor -
Article: Budesonide use in pediatric Crohn disease.
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ABSTRACT: Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD. Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined. BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months. BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.Journal of pediatric gastroenterology and nutrition 01/2012; 55(2):200-4. · 2.18 Impact Factor -
Article: Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis.
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ABSTRACT: We evaluated the efficacy and safety of infliximab for inducing and maintaining benefit in children with moderately to severely active ulcerative colitis (UC). Patients (6-17 years old) who had active UC (Mayo scores of 6-12; endoscopic subscores ≥ 2) and had not responded to or tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and 6. The primary end point was response at week 8 (decreases in Mayo scores ≥ 30% and ≥ 3 points and decreases in rectal bleeding subscores of ≥ 1 or an absolute subscore of ≤ 1). At week 8, only responders were randomly assigned to groups given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54. Maintenance end points included pediatric UC activity index scores <10 points, defined as remission. At week 8, infliximab induced a response in 73.3% of patients (44 of 60) (95% confidence interval, 62.1%-84.5%; a positive result was defined by 95% confidence interval lower limit >40%). Among responders, twice as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of 22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the overall remission rate at week 54 would be 28.6%. Serious adverse events and infusion reactions occurred in similar proportions in the q8w and q12w groups. No deaths, malignancies, opportunistic infections, tuberculosis, or delayed hypersensitivity reactions were reported. Infliximab was safe and effective, inducing a response at week 8 in 73.3% of pediatric patients with moderate to severely active UC who did not respond to conventional therapy. The overall remission rate at week 54 for all enrolled patients was 28.6%, assuming the more effective q8w remission rate.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2011; 10(4):391-9.e1. · 5.64 Impact Factor -
Article: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both? A systematic evaluation in pediatric ulcerative colitis.
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ABSTRACT: There has not been an extensive comparison of CRP and ESR in ulcerative colitis (UC), and thus, we aimed to explore their utility in UC. Four previously enrolled cohorts of 451 children with UC were utilized, all including laboratory, clinical and endoscopic data. A longitudinal analysis was performed on prospectively collected data of 75 children. Disease activity was captured by both global assessment and pediatric UC activity index (PUCAI). The best thresholds to differentiate quiescent, mild, moderate and severe disease activity, were <23, 23-29, 30-37, >37 mm/h for ESR, and <2.5, 2.5-5, 5.01-9, >9 mg/L for CRP (area under the ROC curves 0.70-0.81). Correlation of endoscopic appearance with CRP and ESR were 0.55 and 0.41, respectively (P<0.001). Both CRP and ESR may be completely normal in 34% and 5-10% of those with mild and moderate-severe disease activity, respectively. Elevated CRP in the presence of normal ESR or vice versa was noted in 32%, 38%, 30% and 17% of those with quiescent, mild, moderate and severe disease activity. Over time, the utility of CRP and ESR in reflecting disease activity remained stable in 70-80% of cases. In ~2/3 of children, both CRP and ESR values reflect disease activity to a similar degree and in the remaining, either CRP or ESR may be sufficient, with slight superiority of CRP. CRP is more closely correlated with endoscopic appearance. When either CRP or ESR performs well for a given patient, this is likely to remain so over time. Therefore, it may not be justified to routinely test both ESR and CRP in monitoring disease activity.Journal of Crohn s and Colitis 10/2011; 5(5):423-9. · 2.57 Impact Factor -
Article: Inflammatory bowel disease in adolescents: what problems does it pose?
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ABSTRACT: Adolescents with inflammatory bowel disease face daily and long-term challenges that may be difficult for teenagers to manage. The developmental and psychosocial changes unique to this age group include becoming more autonomous and being more vulnerable to peer influence. These changes may lead to problems in medical management such as poor medication adherence and risky behavior. Being aware of these issues will help the medical team provide anticipatory guidance to address these concerns.World Journal of Gastroenterology 06/2011; 17(22):2691-5. · 2.47 Impact Factor
