Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives

Konstantinos Papamichael¹, Waqqas Afif², David Drobne³, Marla C Dubinsky⁴, Marc Ferrante⁵, Peter M Irving⁶, Nikolaos Kamperidis⁷, Taku Kobayashi⁸, Paulo G Kotze⁹, Jo Lambert¹⁰, Nurulamin M Noor¹¹, Xavier Roblin¹², Giulia Roda¹³, Niels Vande Casteele¹⁴, Andres J Yarur¹⁵, Naila Arebi⁷, Silvio Danese¹³, Stephane Paul¹², William J Sandborn¹⁴, Séverine Vermeire⁵, Adam S Cheifetz¹⁶, Laurent Peyrin-Biroulet¹⁷; International Consortium for Therapeutic Drug Monitoring

Affiliations

¹ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: kpapamic@bidmc.harvard.edu.
² Department of Medicine, Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada.
³ Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
⁴ Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ KU Leuven, Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
⁶ Gastroenterology, Guy's and St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷ Department of IBD, St Mark's Hospital, Imperial College London, London, UK.
⁸ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁹ Catholic University of Paraná (PUCPR), Curitiba, Brazil.
¹⁰ Department of Head and Skin, Ghent University Hospital, Ghent, Belgium.
¹¹ Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹² Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.
¹³ IBD Center, Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
¹⁴ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹⁵ Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁶ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Gastroenterology, Nancy University Hospital, Nancy, France; INSERM U1256 NGERE, Lorraine University, Nancy, France.

PMID: 35026171
PMCID: PMC10187071
DOI: 10.1016/S2468-1253(21)00223-5

Review

Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives

Konstantinos Papamichael et al. Lancet Gastroenterol Hepatol. 2022 Feb.

. 2022 Feb;7(2):171-185.

doi: 10.1016/S2468-1253(21)00223-5.

Authors

Affiliations

¹ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: kpapamic@bidmc.harvard.edu.
² Department of Medicine, Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada.
³ Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
⁴ Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ KU Leuven, Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
⁶ Gastroenterology, Guy's and St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁷ Department of IBD, St Mark's Hospital, Imperial College London, London, UK.
⁸ Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
⁹ Catholic University of Paraná (PUCPR), Curitiba, Brazil.
¹⁰ Department of Head and Skin, Ghent University Hospital, Ghent, Belgium.
¹¹ Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
¹² Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.
¹³ IBD Center, Humanitas Clinical and Research Center-IRCCS, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
¹⁴ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
¹⁵ Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁶ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Gastroenterology, Nancy University Hospital, Nancy, France; INSERM U1256 NGERE, Lorraine University, Nancy, France.

PMID: 35026171
PMCID: PMC10187071
DOI: 10.1016/S2468-1253(21)00223-5

Abstract

Therapeutic drug monitoring (TDM) has emerged as a useful tool for optimising the use of biologics, and in particular anti-tumour necrosis factor (anti-TNF) therapy, in inflammatory bowel disease (IBD). However, challenges remain and are hindering the widespread implementation of TDM in clinical practice. These barriers include identification of the optimal drug concentration to target, the lag time between sampling and results, and the proper interpretation of anti-drug antibody titres among different assays. Solutions to overcome these barriers include the harmonisation of TDM assays and the use of point-of-care testing. Other unmet needs include well designed prospective studies and randomised controlled trials focusing on proactive TDM, particularly during induction therapy. Future studies should also investigate the utility of TDM for biologics other than anti-TNF therapies in both IBD and other immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis, and the use of pharmacokinetic modelling dashboards and pharmacogenetics towards individual personalised medicine.

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Conflict of interest statement

Declaration of interests KP has received a lecture fee from Mitsubishi Tanabe Pharma and Physicians Education Resource; a consultancy fee from Prometheus Laboratories; and scientific advisory board fees from ProciseDx and Scipher Medicine Corporation. NVC has received research grants and personal fees from R-Biopharm, Takeda, and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus Laboratories. ASC has received consultancy fees from AbbVie, Janssen, Takeda, Bacainn, Arena Pharmaceuticals, Grifols, Prometheus Laboratories, Samsung, Bristol Myers Squibb, and Pfizer; and research support from Inform Diagnostics. SV has received grants from AbbVie, Johnson and Johnson, Pfizer, and Takeda; consultancy fees from AbbVie, Arena Pharmaceuticals, Avaxia, Boehringer Ingelheim, Celgene, Dr Falk Pharma, Ferring, Galapagos, Genentech (Roche), Gilead, Hospira, Janssen, Mundipharma, Merck Sharp & Dohme, Pfizer, Prodigest, Progenity, Prometheus Biosciences, Alimentiv, Second Genome, Shire, Takeda, Theravance, and Tillots Pharma; and speaker fees from AbbVie, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Janssen, Pfizer, Shire, Takeda, and Tillots Pharma. NA has received a grant from Pfizer and lecture fees from Janssen, Pfizer, and Takeda. TK reports personal fees from Alfresa Pharma, Covidien, Eli Lilly, Ferring Pharmaceuticals, Janssen, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kyaku, Pfizer, Takeda Pharmaceutical, Thermo Fisher Scientific, AbbVie, Astellas, Celltrion, EA Pharma, Nippon Kyaku, Mochida Pharmaceutical, Mitsubishi Tanabe Pharma, Zeria Pharmaceutical, Gilead Sciences, Janssen, and JIMRO; and grants from AbbVie, EA Pharma, Otsuka Holdings, Zeria Pharmaceutical, Kyorin Pharmaceutical, Mochida Pharmaceutical, Thermo Fisher Scientific, Alfresa Pharma, and Nippon Kyaku. WJS reports research grants from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda, and Theravance Biopharma; consultancy fees from AbbVie, Abivax, Admirx, Alfasigma, Alimentiv, Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Salix (Bausch Health), Beigene, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Genentech (Roche), Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic, Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences, and Zealand Pharma; and stock or stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Prometheus Laboratories, Progenity, Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences, and Vivreon Biosciences. PMI reports lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Falk Pharma, Ferring, Gilead, Merck Sharp & Dohme, Janssen, Pfizer, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire, and Warner Chilcott; financial support for research from Merck Sharp & Dohme, Pfizer, and Takeda; and advisory fees from AbbVie, Arena Pharmaceuticals, Genentech, Gilead, Hospira, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, Pharmacosmos, Procise, Prometheus Biosciences, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VHsquared, Vifor Pharma, and Warner Chilcott. MF reports financial support for research from AbbVie, Amgen, Biogen, Janssen, Pfizer, and Takeda; consultancy fees from AbbVie, Boehringer-Ingelheim, Celltrion, Janssen, Lilly, Medtronic, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, and Thermo Fisher Scientific; and speaker fees from AbbVie, Amgen, Biogen, Boehringer-Ingelheim, Falk, Ferring, Janssen, Lamepro, Merck Sharp & Dohme, Mylan, Pfizer, Sandoz, Takeda, and Truvion Healthcare. PGK has received consultancy and speaker fees from AbbVie, Janssen, Pfizer, Takeda, Ferring, and Novartis; and scientific grants from Takeda and Pfizer. DD has served as a speaker, a consultant, and an advisory board member for Merck Sharp & Dohme, AbbVie, Takeda, Pfizer, Janssen, Amgen, Biogen, and Krka. JL has received unrestricted grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB; speaker fees for AbbVie, Almirall, BMS, Janssen-Cilag, Pfizer, and UCB; and consultancy fees for AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB. NK has received speaker fees from Janssen. WA has received consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Dynacare, Janssen, Merck, Novartis, Pfizer, Sandoz, and Takeda. AJY has received consultant or advisory board fees from Prometheus Laboratories, Takeda, Arena Pharmaceuticals, and Bristol Myers Squibb. SD has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Merck Sharp & Dohme, UCB, Ferring, Cellerix, Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor Pharma, Johnson and Johnson, Nikkiso Europe, and Theravance. MCD has received consultancy fees from Janssen, AbbVie, Pfizer, Takeda, UCB, Celgene, Bristol Myers Squibb, Prometheus Biosciences, Arena Pharmaceuticals, and Lilly; and grant support from AbbVie, Pfizer, and Janssen. LPB has received grant support from AbbVie, Merck Sharp & Dohme, and Takeda; consulting fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger-Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, Merck Sharp & Dohme, Roche, Arena Pharmaceuticals, Gilead, Hikma, Amgen, Bristol Myers Squibb, Vifor, Norgine, Mylan, Lilly, Fresenius, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, and Enthera; and stock or stock options from Clinical Trials Mobile Application. All other authors declare no competing interests.

Figures

**Figure 1:. Future perspectives of therapeutic drug monitoring of biologics in IBD.**
PK: pharmacokinetic; TDM: therapeutic drug monitoring; HLA: human leukocyte antigen; SNP: Single nucleotide polymorphisms; CRP: C-reactive protein; ADA: anti-drug antibodies; HBI: Harvey-Bradshaw index; CDAI: clinical disease activity index; PMS: partial Mayo score; BMI: body mass index; IMM: immunomodulator; POC: point of care; DBS: dried blood spots.

See this image and copyright information in PMC

References

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Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives

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Therapeutic drug monitoring of biologics in inflammatory bowel disease: unmet needs and future perspectives

Authors

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Abstract

Conflict of interest statement

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