The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease

a post hoc analysis

Jeffrey S. Hyams, Marla Dubinsky, Joel Rosh, Frank M. Ruemmele, Samantha F. Eichner, Jen Fue Maa, Andreas Lazar, Gabriela Alperovich, Nael M. Mostafa, Anne M. Robinson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. Aim: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. Methods: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). Results: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups. Conclusions: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.

Original languageEnglish (US)
Pages (from-to)155-164
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume49
Issue number2
DOIs
StatePublished - Jan 1 2019

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Immunologic Factors
Crohn Disease
Pharmacokinetics
Pediatrics
Safety
Adalimumab
Serum
Research Personnel
Weights and Measures
Therapeutics
Infection

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Hyams, Jeffrey S. ; Dubinsky, Marla ; Rosh, Joel ; Ruemmele, Frank M. ; Eichner, Samantha F. ; Maa, Jen Fue ; Lazar, Andreas ; Alperovich, Gabriela ; Mostafa, Nael M. ; Robinson, Anne M. / The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease : a post hoc analysis. In: Alimentary Pharmacology and Therapeutics. 2019 ; Vol. 49, No. 2. pp. 155-164.
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title = "The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease: a post hoc analysis",
abstract = "Background: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. Aim: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. Methods: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). Results: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79{\%}; 87{\%}; P = 0.235) and remission (26{\%}; 30{\%}; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68{\%}; 55{\%}; P = 0.086) or remission (41{\%}; 30{\%}; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56{\%}; 46{\%}; P = 0.189) or remission (38{\%}; 33{\%}; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7{\%}; 6{\%}) were not significantly different between groups. Conclusions: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.",
author = "Hyams, {Jeffrey S.} and Marla Dubinsky and Joel Rosh and Ruemmele, {Frank M.} and Eichner, {Samantha F.} and Maa, {Jen Fue} and Andreas Lazar and Gabriela Alperovich and Mostafa, {Nael M.} and Robinson, {Anne M.}",
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The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease : a post hoc analysis. / Hyams, Jeffrey S.; Dubinsky, Marla; Rosh, Joel; Ruemmele, Frank M.; Eichner, Samantha F.; Maa, Jen Fue; Lazar, Andreas; Alperovich, Gabriela; Mostafa, Nael M.; Robinson, Anne M.

In: Alimentary Pharmacology and Therapeutics, Vol. 49, No. 2, 01.01.2019, p. 155-164.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn’s disease

T2 - a post hoc analysis

AU - Hyams, Jeffrey S.

AU - Dubinsky, Marla

AU - Rosh, Joel

AU - Ruemmele, Frank M.

AU - Eichner, Samantha F.

AU - Maa, Jen Fue

AU - Lazar, Andreas

AU - Alperovich, Gabriela

AU - Mostafa, Nael M.

AU - Robinson, Anne M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. Aim: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. Methods: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). Results: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups. Conclusions: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.

AB - Background: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. Aim: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. Methods: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). Results: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups. Conclusions: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.

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