Read by QxMD icon Read

Infliximab therapeutic drug monitoring

Bella Ungar, Yoav Glidai, Miri Yavzori, Orit Picard, Ella Fudim, Avishay Lahad, Yael Haberman, Dror S Shouval, Ilana Weintraub, Rami Eliakim, Shomron Ben-Horin, Batia Weiss
OBJECTIVES: While infliximab pharmacokinetics are associated with therapy outcome in adult IBD population, limited data is available in pediatric patients. We aimed to define the relationship between Infliximab trough and antibodies' levels (IFX-TL, ATI) and clinical, biomarker remission. METHODS: IFX-TL and ATI were routinely obtained between 2011-2017. Associations with clinical and inflammatory (C-reactive protein, CRP) end-points were studied throughout the first year of infliximab therapy...
June 12, 2018: Journal of Pediatric Gastroenterology and Nutrition
Sara Lega, Becky L Phan, Casey J Rosenthal, Julia Gordon, Nichola Haddad, Nanci Pittman, Keith J Benkov, Marla C Dubinsky
Background: Infliximab (IFX) discontinuation is not uncommon during the first year of treatment due to inadequate drug concentrations and anti-IFX antibodies (ATI). Both combination therapy and proactive therapeutic drug monitoring (pTDM) are used to decrease ATI and increase IFX durability. We proposed that monotherapy (Mono) is as effective as combination therapy (Combo) if the first maintenance infusion is dosed based on week 10 pTDM. Methods: In a retrospective cohort of 83 patients with inflammatory bowel disease (IBD), we examined the frequency of IFX discontinuation, ATI, infusion reactions, and IFX concentrations during the first year of treatment in patients receiving week 10 pTDM-guided IFX monotherapy (Mono pTDM; n = 16) compared with patients on mono (n = 32) or combination therapy (n = 35) in whom TDM was introduced at or after week 14, per standard of care (SOC)...
June 2, 2018: Inflammatory Bowel Diseases
Bella Ungar, Tal Engel, Doron Yablecovitch, Adi Lahat, Alon Lang, Benjamin Avidan, Ofir Har-Noy, Dan Carter, Nina Levhar, Limor Selinger, Sandra Neuman, Ola Haj Natour, Miri Yavzori, Ella Fudim, Orit Picard, Uri Kopylov, Yehuda Chowers, Timna Naftali, Efrat Broide, Eyal Shachar, Rami Eliakim, Shomron Ben-Horin
OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels...
June 5, 2018: American Journal of Gastroenterology
Karien Bloem, Tiny Schaap, Ronald Boshuizen, Eva L Kneepkens, Gerrit J Wolbink, Annick de Vries, Theo Rispens
AIM: For assessment of concentrations of biopharmaceuticals, for example, therapeutic drug monitoring, dried blood sampling of capillary blood is a convenient alternative to traditional venepuncture sampling. We investigated an alternative to dried blood spot collection on filter paper: sampling capillary blood using the Mitra® microsampler. MATERIALS AND METHODS:  Therapeutic monoclonal antibodies were spiked in whole blood, sampled using filter paper and Mitra microsampler and concentrations measured using specific ELISAs...
June 4, 2018: Bioanalysis
Luisa Guidi, Daniela Pugliese, Tommaso Panici Tonucci, Alexandra Berrino, Barbara Tolusso, Michele Basile, Laura Cantoro, Paola Balestrieri, Fortunata Civitelli, Lorenzo Bertani, Manuela Marzo, Carla Felice, Elisa Gremese, Francesco Costa, Franca Viola, Michele Cicala, Anna Kohn, Antonio Gasbarrini, Gian Lodovico Rapaccini, Matteo Ruggeri, Alessandro Armuzzi
Background: Empirical dose intensification and therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels (ITL) and antibody (ATI) assays are recognised approaches for managing the loss of response (LoR) in inflammatory bowel disease (IBD) patients. Aim: To compare these two interventions in a clinical setting, in terms of effectiveness and cost savings. Methods: Consecutive IBD patients, experiencing LoR, were clinically managed according to a TDM algorithm...
May 31, 2018: Journal of Crohn's & Colitis
J German Sanchez-Hernandez, Noemi Rebollo, Fernando Muñoz, Ana Martin-Suarez, Maria Victoria Calvo
BACKGROUND: Tumour necrosis factor inhibitor (TNFi) therapy has drastically changed the management of chronic inflammatory diseases (CID). Some important drawbacks that can cause loss of response during treatment with these drugs are related to their large individual variability, the disease burden and the formation of anti-drug-antibodies (ADA) that increase its clearance. Therapeutic drug monitoring (TDM) of these drugs is not yet recommended by all scientific societies, and if so, only in patients with inflammatory symptoms...
January 1, 2018: Annals of Clinical Biochemistry
Konstantinos Papamichael, Shana Rakowsky, Claudio Rivera, Adam S Cheifetz, Mark T Osterman
Background and aim: Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods: This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016...
April 28, 2018: Inflammatory Bowel Diseases
Sophie Restellini, Che-Yung Chao, Peter L Lakatos, Achuthan Aruljothy, Haya Aziz, Omar Kherad, Alain Bitton, Gary Wild, Waqqas Afif, Talat Bessissow
Background: Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Methods: Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed...
June 8, 2018: Inflammatory Bowel Diseases
Francesca Nencini, Alessandra Vultaggio, Sara Pratesi, Daniele Cammelli, Monica Milla, Ginevra Fiori, Siro Bagnoli, Francesca Prignano, Sergio Romagnani, Enrico Maggi, Andrea Matucci
BACKGROUND: Hypersensitivity reactions (HRs) and loss of response (LOR) to infliximab (IFX) are related to drug immunogenicity characterized by antidrug antibodies (ADAs). OBJECTIVE: To analyze the timing of ADA appearance and its relationship with drug levels and clinical outcomes in IFX-treated patients with different diseases. METHODS: Samples were longitudinally collected before each infusion from 91 IFX-treated patients and were assayed for ADA and drug levels by enzyme-linked immunosorbent assay and for IgE by ImmunoCAP system...
April 13, 2018: Journal of Allergy and Clinical Immunology in Practice
Jean-François Jourdil, Benjamin Némoz, Elodie Gautier-Veyret, Charlotte Romero, Françoise Stanke-Labesque
BACKGROUND: Adalimumab (ADA) and infliximab (IFX) are therapeutic monoclonal antibodies (TMabs) targeting tumor necrosis factor-alpha (TNFα). They are used to treat inflammatory diseases. Clinical trials have suggested that therapeutic drug monitoring for ADA or IFX could improve treatment response and cost-effectiveness. However, ADA and IFX were quantified by ELISA in all these studies, and the discrepancies between the results obtained raise questions about their reliability.We describe here the validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of ADA and IFX in human samples...
March 30, 2018: Therapeutic Drug Monitoring
Mandica Vidovic, Lovro Lamot, Mirta Lamot, Miroslav Harjacek
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, with heterogeneous clinical features. Although therapeutic options are wide and in the majority of children symptoms improve with the combination of non-steroidal anti-inflammatory and disease-modifying drugs, there are a number of patients who do not respond to conventional therapy and who do not meet the criteria for systemic biologics, namely anti TNF-alpha. Those patients are potential candidates for intraarticular therapy with biologics and in this report we present the results of intra-articular infliximab treatment in a series of patients diagnosed with oligoarticular subtype of JIA...
March 21, 2018: Clinical and Experimental Rheumatology
Konstantinos Papamichael, Ravy K Vajravelu, Byron P Vaughn, Mark T Osterman, Adam S Cheifetz
Background and aims: Reactive testing has emerged as the new standard of care for managing loss of response to infliximab in inflammatory bowel disease (IBD). Recent data suggest that proactive infliximab monitoring is associated with better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the clinical utility of proactive infliximab monitoring after first reactive testing. We aimed to evaluate long-term outcomes of proactive infliximab monitoring following reactive testing compared to reactive testing alone in patients with IBD...
March 24, 2018: Journal of Crohn's & Colitis
Rohini Vanga, Millie D Long
PURPOSE OF REVIEW: We discuss the newest evidence-based data on management of ulcerative colitis (UC). We emphasize risk-stratification, optimizing medical therapies, and surgical outcomes of UC. RECENT FINDINGS: Recent medical advances include introduction of novel agents for UC. Vedolizumab, an anti-adhesion molecule, has demonstrated efficacy in moderate to severe UC. Tofacitinib, a small molecule, has also demonstrated efficacy. Data on optimization of infliximab show the superiority of combination therapy with azathioprine over monotherapy with infliximab or azathioprine alone...
March 27, 2018: Current Gastroenterology Reports
Abisoye O Akintimehin, Ríoghnach Sinead O'Neill, Conor Ring, Tara Raftery, Séamus Hussey
Aim: All Irish children with ulcerative colitis (UC) attend the National Centre for Paediatric Gastroenterology at Our Lady's Children's Hospital, Crumlin. The aim of this study was to determine the outcomes of children with acute severe ulcerative colitis (ASC) and the impact of infliximab on these outcomes following its introduction for this indication in 2011. Methods: A retrospective chart review of all patients admitted with ASC between January 1, 2009 and December 31, 2015 was undertaken...
2018: Frontiers in Pediatrics
Frank I Scott, Gary R Lichtenstein
PURPOSE OF REVIEW: Monoclonal antibodies targeting tumor necrosis factor-alpha, integrin molecules, and interleukin-12/23 have become backbone therapies for Crohn's disease and ulcerative colitis. While clinically effective, these biologic therapies come with significant expense, contributing to overall healthcare spending in the USA. Biosimilars have the potential to significantly reduce expenditures secondary to the use of biologic medications such as infliximab and adalimumab, though their complicated manufacturing process results in inherent differences in structure when compared to the originator compounds...
March 2018: Current Treatment Options in Gastroenterology
Juliette Sheridan, Carol Ann Coe, Peter Doran, Laurence Egan, Garret Cullen, David Kevans, Jan Leyden, Marie Galligan, Aoibhlinn O'Toole, Jane McCarthy, Glen Doherty
Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC...
2018: BMJ Open Gastroenterology
Travis Piester, Adam Frymoyer, Megan Christofferson, Helen Yu, Dorsey Bass, K T Park
Background: Inadequate infliximab (IFX) drug exposure remains a clinical challenge and leads to high loss of response rates and therapy failure in inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for therapy optimization. Methods: We developed an mIDC leveraging the known clinical variables of C-reative protein (CRP), albumin, patient's weight, disease activity indices, calprotectin, drug trough levels, and antibodies to IFX that significantly affect pharmacokinetics and/or outcomes...
January 18, 2018: Inflammatory Bowel Diseases
Konstantinos Papamichael, Ravy K Vajravelu, Mark T Osterman, Adam S Cheifetz
BACKGROUND: Preliminary data suggest that treatment optimization can reverse immunogenicity and regain response in patients with IBD and secondary loss of response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data regarding the long-term outcome of these patients are scarce. AIMS: We aimed to investigate drug retention in IBD patients of whom infliximab was optimized to overcome immunogenicity and variables associated with drug retention. METHODS: This was a retrospective, multicenter study of consecutive IBD patients with antibodies to infliximab (ATI), based on either proactive or reactive therapeutic drug monitoring, who underwent infliximab optimization (increasing dose, shortening interval, adding an immunomodulator, or combination) to overcome immunogenicity from September 2012 to July 2015; they were followed through December 2015...
January 16, 2018: Digestive Diseases and Sciences
Amy Hemperly, Niels Vande Casteele
Infliximab was the first monoclonal antibody to be approved for the treatment of pediatric and adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC). It has been shown to induce and maintain both clinical remission and mucosal healing in pediatric and adult patients with inflammatory bowel disease (IBD) who are unresponsive or refractory to conventional therapies. The administration of infliximab is weight-based and the drug is administered intravenously. The volume of distribution of infliximab is low and at steady state ranges from 4...
January 12, 2018: Clinical Pharmacokinetics
Geert D'Haens, Severine Vermeire, Guy Lambrecht, Filip Baert, Peter Bossuyt, Benjamin Pariente, Anthony Buisson, Yoram Bouhnik, Jérôme Filippi, Janneke Vander Woude, Philippe Van Hootegem, Jacques Moreau, Edouard Louis, Denis Franchimont, Martine De Vos, Fazia Mana, Laurent Peyrin-Biroulet, Hedia Brixi, Matthieu Allez, Philip Caenepeel, Alexandre Aubourg, Bas Oldenburg, Marieke Pierik, Ann Gils, Sylvie Chevret, David Laharie
BACKGROUND & AIMS: A combination of infliximab and immunomodulators is the most efficacious treatment for Crohn's disease (CD). Patients have the best outcomes when their serum concentrations of these drugs are above a determined therapeutic threshold. We performed a prospective, randomized trial to determine whether therapeutic drug monitoring (TDM) to maintain serum levels of infliximab above 3 μg/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms...
April 2018: Gastroenterology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"