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Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies: A case report of infantile-onset inflammatory bowel disease
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Ancona, Silvana
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Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Signa, Sara
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IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Longo, Chiara
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Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy
IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Cangemi, Giuliana
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IRCCS Ist Giannina Gaslini, Chromatog & Mass Spectrometry Sect, Cent Lab Anal, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Carfora, Roberta
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Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Drago, Enrico
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Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

La Rosa, Alessandro
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Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy
IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Crocco, Marco
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IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Chiaro, Andrea
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IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Gandullia, Paolo
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IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy

Arrigo, Serena
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IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy
机构:
[1] Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, I-16126 Genoa, Italy
[2] IRCCS Ist Giannina Gaslini, Pediat Gastroenterol & Endoscopy Unit, 5 Via Gerolamo Gaslini, I-16147 Genoa, Italy
[3] IRCCS Ist Giannina Gaslini, Chromatog & Mass Spectrometry Sect, Cent Lab Anal, I-16147 Genoa, Italy
关键词:
Infantile-onset inflammatory bowel disease;
Adalimumab;
Loss of response;
Dose escalation;
Anti-drug antibodies;
Case report;
COMBINATION THERAPY;
INFLIXIMAB THERAPY;
PEDIATRIC-PATIENTS;
CHILDREN;
IMMUNOMODULATORS;
AGE;
D O I:
10.3748/wjg.v29.i38.5428
中图分类号:
R57 [消化系及腹部疾病];
学科分类号:
摘要:
BACKGROUNDTreatment 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 SUMMARYA 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.CONCLUSIONTDM-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.
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页码:5428 / 5434
页数:7
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Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Peeters, M.
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Compernolle, G.
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Tops, S.
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Van Steen, K.
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ULg, GIGA R Med Genom Lab BIO3, Liege, Belgium
Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Van Assche, G.
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Katholieke Univ Leuven, Translat Res GastroIntestinal Disorders TARGID, Dept Clin & Expt Med, Leuven, Belgium
Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Ferrante, M.
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Katholieke Univ Leuven, Translat Res GastroIntestinal Disorders TARGID, Dept Clin & Expt Med, Leuven, Belgium
Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Vermeire, S.
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Katholieke Univ Leuven, Translat Res GastroIntestinal Disorders TARGID, Dept Clin & Expt Med, Leuven, Belgium
Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium

Gils, A.
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Therapeut & Diagnost Antibodies, Leuven, Belgium