Safety and Efficacy of Adalimumab for Moderate to Severe Crohn's Disease in Children
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.
- SourceAvailable from: Edwin F De Zoeten
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- "This study included a very small number of UC subjects and larger studies are required to determine the efficacy of adalimumab in pediatric UC. There is promising data on adalimumab’s use in pediatric Crohn’s disease for patients with refractory disease, with loss of response or an adverse reaction to infliximab, with clinical remission rates reported between 22 and 42% [78, 79]. To date, there are no reports on the use of certolizumab pegol in the treatment of pediatric UC. "
ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that has significant morbidities in the pediatric population. Goals of medical therapy include induction and maintenance of remission while preserving the colon and it’s function, while minimizing the risk of treatment related morbidities. For those children who do not respond to initial therapies and progress to develop moderately-to-severely active UC, there has been a dearth of available treatments to help induce remission, necessitating long-term corticosteroid usage, with associated comorbidities of chronic steroid treatment. Significant advances have been made in medical management, including the use of biologic therapies, specifically anti-tumor necrosis factor-α monoclonal antibodies. With the Food and Drug Administration’s recent approval of the use of infliximab, a chimeric anti-tumor necrosis factor-α antibody, for children ≥6 years of age with moderately-to-severely active UC, care providers now have a new treatment regimen to offer this pediatric population.06/2013; 3(1). DOI:10.1007/s13554-012-0006-1
- Journal of pediatric gastroenterology and nutrition 09/2012; 55(5). DOI:10.1097/MPG.0b013e318272af1f · 2.63 Impact Factor
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ABSTRACT: Ulcerative colitis is a chronic, idiopathic, inflammatory disease of the colon and rectum that may be associated with growth failure, nutritional derangements and psychosocial ramifications in affected children. Multiple medical options are available to achieve disease remission; however, some of these medications can have unwanted side effects, especially in younger patients. With increased understanding of the etiology of the disease, newer therapeutic alternatives have arisen in the form of biologic therapies, namely monoclonal antibodies targeted to a specific protein or receptor. Specifically, infliximab, an anti-TNF-α agent, has been shown to be safe and effective for the treatment of moderate-to-severe pediatric ulcerative colitis.Expert review of gastroenterology & hepatology 12/2012; 6(6):659-65. DOI:10.1586/egh.12.53 · 2.42 Impact Factor