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.
- Journal of pediatric gastroenterology and nutrition 09/2012; DOI:10.1097/MPG.0b013e318272af1f · 2.87 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 · 2.55 Impact Factor
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ABSTRACT: BACKGROUND: Adalimumab (ADA) is a subcutaneous anti-tumour necrosis factor (anti-TNF) agent, effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab (IFX), ADA dosing is not weight adjusted and dose frequency is based on clinical response. AIM: To determine whether obesity is a risk factor for early loss of response (LOR) to anti-TNF treatment and whether weight-adjusted anti-TNF treatment is favourable. MATERIALS AND METHODS: A hospital database of CD patients receiving anti-TNF treatment was analyzed retrospectively. The relationship between time to LOR and BMI was examined by Kaplan-Meier (KM) survival curves and a Cox proportional hazards model. RESULTS: ADA patients: Of the 54 patients (46 BMI<30 and 8 BMI≥30), KM estimation indicated a significantly shorter time to dose escalation in the BMI of at least 30 (χ=6.117, P=0.01). The Cox proportional hazards model showed that an increased hazard of LOR to ADA is related to increases in BMI (P=0.04). IFX patients: Of the 76 patients (62 BMI<30 and 14 BMI≥30), KM estimation showed that the differences in survival curves were not significant (χ=1.933, P=0.16) for the BMI groups. This was supported by the Cox proportional hazard model (P=0.36). CONCLUSION: BMI appears to be important in predicting ADA efficacy (LOR) in CD. IFX appears to overcome this reduction of efficacy in obese patients. A prospective study evaluating the effect of weight on anti-TNF drug response and serum drug levels is warranted.European journal of gastroenterology & hepatology 01/2013; DOI:10.1097/MEG.0b013e32835d1f15 · 2.15 Impact Factor