Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn's Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial.


Journal

Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162

Informations de publication

Date de publication:
23 10 2020
Historique:
received: 20 09 2019
pubmed: 4 12 2019
medline: 21 10 2021
entrez: 4 12 2019
Statut: ppublish

Résumé

The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

Sections du résumé

BACKGROUND
The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction.
METHODS
Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies.
RESULTS
Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group.
CONCLUSIONS
Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

Identifiants

pubmed: 31793630
pii: 5650717
doi: 10.1093/ibd/izz294
doi:

Substances chimiques

Anti-Inflammatory Agents 0
Immunologic Factors 0
Leukocyte L1 Antigen Complex 0
C-Reactive Protein 9007-41-4
Adalimumab FYS6T7F842

Banques de données

ClinicalTrials.gov
['NCT02256462']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1627-1635

Informations de copyright

© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Manar Matar (M)

The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel.

Raanan Shamir (R)

The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel.
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Dan Turner (D)

The Juliet Keidan Institute of Pediatric Gastroenterology, Nutrition, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel.

Efrat Broide (E)

The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel.

Batia Weiss (B)

The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Gastroenterology Unit, Sheba Medical Center, Edmond and Lily Safra Childen's Hospital, Ramat-Gan, Tel-Hashomer, Israel.

Oren Ledder (O)

The Juliet Keidan Institute of Pediatric Gastroenterology, Nutrition, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel.

Anat Guz-Mark (A)

The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel.
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Firas Rinawi (F)

The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel.
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Shlomi Cohen (S)

The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Gastroenterology Unit, "Dana-Dwek" Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.

Chani Topf-Olivestone (C)

Pediatric Gastroenterology Unit, Kaplan Medical Center, Rehovot, Israel.

Ron Shaoul (R)

Pediatric Gastroenterology Unit, Rambam Medical Center, Haifa, Israel.

Baruch Yerushalmi (B)

Pediatric Gastroenterology Unit, Saban Pediatric Medical Center, Soroka University Hospital and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Shomron Ben-Horin (S)

The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Tel-Hashomer, Israel.

Amit Assa (A)

The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel.
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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