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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies: A case report of infantile-onset inflammatory bowel disease
Silvana Ancona, Sara Signa, Chiara Longo, Giuliana Cangemi, Roberta Carfora, Enrico Drago, Alessandro La Rosa, Marco Crocco, Andrea Chiaro, Paolo Gandullia, Serena Arrigo
Silvana Ancona, Chiara Longo, Roberta Carfora, Enrico Drago, Alessandro La Rosa, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, Genova 16126, Italy
Sara Signa, Chiara Longo, Alessandro La Rosa, Marco Crocco, Andrea Chiaro, Paolo Gandullia, Serena Arrigo, Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, Genova 16147, Italy
Giuliana Cangemi, Chromatography and Mass Spectrometry Section, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, Genova 16147, Italy
Author contributions: Ancona S, Signa S, Longo C, Carfora R, and Drago E contributed to manuscript writing and editing, and data collection; Cangemi G contributed to therapeutic drug monitoring and data collection; Arrigo S, Gandullia P, Crocco M, La Rosa A, and Chiaro A contributed to conceptualization and supervision; and all authors read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patients for the publication of this report and any accompanying images.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Serena Arrigo, MD, Staff Physician, Pediatric Gastroenterology and Endoscopy Unit, IRCCS Istituto Giannina Gaslini, 5 Via Gerolamo Gaslini, Genova 16147, Italy. serenaarrigo@gaslini.org
Received: June 7, 2023
Peer-review started: June 7, 2023
First decision: July 7, 2023
Revised: July 21, 2023
Accepted: July 27, 2023
Article in press: July 27, 2023
Published online: October 14, 2023
BACKGROUND
Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics. Secondary loss of response is frequently caused by the production of anti-drug antibodies, a well-known problem in IBD patients on biologic treatment. We present a case of IO-IBD treated with therapeutic drug monitoring (TDM)-guided high-dose anti-tumor necrosis factor therapy, in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.
CASE SUMMARY
A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life, as well as relapsing perianal abscess and growth failure. Hypoalbuminemia, anemia, and elevated inflammatory markers were also present. Endoscopic assessment revealed skip lesions with deep colic ulcerations, inflammatory anal sub-stenosis, and deep fissures with persistent abscess. A diagnosis of IO-IBD Crohn-like was made. The patient was initially treated with oral steroids and fistulotomy. After the perianal abscess healed, adalimumab (ADA) was administered with concomitant gradual tapering of steroids. Clinical and biochemical steroid-free remission was achieved with good trough levels. After 3 mo, antibodies to ADA (ATA) were found with undetectable trough levels; therefore, we optimized the therapy schedule, first administering 10 mg weekly and subsequently up to 20 mg weekly (2.8 mg/kg/dose). After 2 mo of high-dose treatment, ATA disappeared, with concomitant high trough levels and stable clinical and biochemical remission of the disease.
CONCLUSION
TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production. This strategy could be a good alternative to combination therapy, especially in very young patients.
Core Tip: Infantile-onset inflammatory bowel disease (IBD) frequently has a more severe course and a greater resistance to standard therapy than IBD in older children. Anti-tumor necrosis factor agents often lead to the production of anti-drug antibodies, resulting in loss of clinical response and disease progression. For this reason, the early detection of anti-drug antibodies is important, which may be possible with therapeutic drug monitoring. To date, commonly used strategies to overcome anti-drug antibodies are switching drugs or adding an immunomodulator, but a better option may be dose escalation.
