Safety and efficacy of adalimumab for moderate to severe crohn's disease in children

Jeffrey S. Hyams, Anne Griffiths, James Markowitz, Robert N. Baldassano, William A. Faubion, Richard B. Colletti, Marla Dubinsky, Jaroslaw Kierkus, Joel Rosh, Yaqin Wang, Bidan Huang, Barry Bittle, Michael Marshall, Andreas Lazar

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131 Citations (Scopus)

Abstract

Background & Aims: 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). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)365-374.e2
JournalGastroenterology
Volume143
Issue number2
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Crohn Disease
Safety
Body Weight
Adalimumab
Therapeutics
Maintenance
Pediatrics
Pediatric Crohn's disease

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Hyams, J. S., Griffiths, A., Markowitz, J., Baldassano, R. N., Faubion, W. A., Colletti, R. B., ... Lazar, A. (2012). Safety and efficacy of adalimumab for moderate to severe crohn's disease in children. Gastroenterology, 143(2), 365-374.e2. https://doi.org/10.1053/j.gastro.2012.04.046
Hyams, Jeffrey S. ; Griffiths, Anne ; Markowitz, James ; Baldassano, Robert N. ; Faubion, William A. ; Colletti, Richard B. ; Dubinsky, Marla ; Kierkus, Jaroslaw ; Rosh, Joel ; Wang, Yaqin ; Huang, Bidan ; Bittle, Barry ; Marshall, Michael ; Lazar, Andreas. / Safety and efficacy of adalimumab for moderate to severe crohn's disease in children. In: Gastroenterology. 2012 ; Vol. 143, No. 2. pp. 365-374.e2.
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abstract = "Background & Aims: 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). Methods: 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. Results: 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. Conclusions: 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.",
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Hyams, JS, Griffiths, A, Markowitz, J, Baldassano, RN, Faubion, WA, Colletti, RB, Dubinsky, M, Kierkus, J, Rosh, J, Wang, Y, Huang, B, Bittle, B, Marshall, M & Lazar, A 2012, 'Safety and efficacy of adalimumab for moderate to severe crohn's disease in children', Gastroenterology, vol. 143, no. 2, pp. 365-374.e2. https://doi.org/10.1053/j.gastro.2012.04.046

Safety and efficacy of adalimumab for moderate to severe crohn's disease in children. / Hyams, Jeffrey S.; Griffiths, Anne; Markowitz, James; Baldassano, Robert N.; Faubion, William A.; Colletti, Richard B.; Dubinsky, Marla; Kierkus, Jaroslaw; Rosh, Joel; Wang, Yaqin; Huang, Bidan; Bittle, Barry; Marshall, Michael; Lazar, Andreas.

In: Gastroenterology, Vol. 143, No. 2, 01.01.2012, p. 365-374.e2.

Research output: Contribution to journalArticle

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T1 - Safety and efficacy of adalimumab for moderate to severe crohn's disease in children

AU - Hyams, Jeffrey S.

AU - Griffiths, Anne

AU - Markowitz, James

AU - Baldassano, Robert N.

AU - Faubion, William A.

AU - Colletti, Richard B.

AU - Dubinsky, Marla

AU - Kierkus, Jaroslaw

AU - Rosh, Joel

AU - Wang, Yaqin

AU - Huang, Bidan

AU - Bittle, Barry

AU - Marshall, Michael

AU - Lazar, Andreas

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Background & Aims: 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). Methods: 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. Results: 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. Conclusions: 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.

AB - Background & Aims: 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). Methods: 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. Results: 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. Conclusions: 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.

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Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA, Colletti RB et al. Safety and efficacy of adalimumab for moderate to severe crohn's disease in children. Gastroenterology. 2012 Jan 1;143(2):365-374.e2. https://doi.org/10.1053/j.gastro.2012.04.046