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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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World Journal of Gastroenterology 2023年第38期29卷 5428-5434页

作者： Silvana Ancona Sara Signa Chiara Longo Giuliana Cangemi Roberta Carfora Enrico Drago Alessandro La Rosa Marco Crocco andrea chiaro Paolo Gandullia Serena Arrigo Dipartimento di Neuroscienze RiabilitazioneOftalmologiaGenetica e Scienze Materno-Infantili(DINOGMI)Universitàdegli Studi di GenovaGenova 16126Italy Pediatric Gastroenterology and Endoscopy Unit IRCCS Istituto Giannina GasliniGenova 16147Italy Chromatography and Mass Spectrometry Section Central Laboratory of AnalysisIRCCS Istituto Giannina GasliniGenova 16147Italy

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 *** loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic *** 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 *** 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 ***,anemia,and elevated inflammatory markers were also *** 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 *** patient was initially treated with oral steroids and *** the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of *** and biochemical steroid-free remission was achieved with good trough *** 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 *** TDM-guided high-dose ADA treatment as a monotherapy overcame ATA *** strategy could be a good alternative to combination therapy,especially in very young patients.

关键词： Infantile-onset inflammatory bowel disease Adalimumab Loss of response Dose escalation Anti-drug antibodies Case report

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Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals

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World Journal of Gastrointestinal Endoscopy 2015年第9期7卷 833-842页

作者： Gabriele Capurso Marianna Signoretti Roberto Valente Urban Arnelo Matthias Lohr Jan-Werner Poley Gianfranco Delle Fave Marco Del chiaro Digestive and Liver Disease Unit S.Andrea HospitalUniversity Sapienza Departments of Gastroenterology and Hepatology Erasmus MCUniversity Medical Center Pancreatic Surgery Unit Division of SurgeryCLINTECKarolinska Institutet at Karolinska University Hospital

Pancreatic ductal adenocarcinoma(PDAC) is a lethal neoplasia, for which secondary prevention(i.e., screening) is advisable for high-risk individuals with "familiar pancreatic cancer" and with other specific genetic syndromes(Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging(MRI) and endoscopic ultrasound(EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.

关键词： Endoscopic ultrasound Pancreatic cancer Screening High-risk individuals Magnetic resonance

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