Implications for sequencing of biologic therapy and choice of second anti‐TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti‐TNF therapy (IMSAT) therapeutic drug monitoring study Article Swipe

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Neil Chanchlani , Simeng Lin , Marcus Auth , Chai Leng Lee , Helena Robbins , Shi Jie Looi , Senthil Murugesan , Tom Riley , Cathryn Preston , Sophie Stephenson , Wendy Cardozo , Sunil Sonwalkar , Mohammed Allah‐Ditta , Lynne Mansfield , Dharmaraj Durai , Mark R. Baker , Ian London , Emily London , Sanjay Gupta , Alex Di Mambro , Aisling Murphy , Edward Gaynor , Kelsey Jones , Andrew Claridge , Shaji Sebastian , Sankaranarayanan Ramachandran , Christian P. Selinger , Simon Borg‐Bartolo , Paul R. Knight , Michael Sprakes , Julie Burton , Patricia Kane , Stephanie Lupton , Aimee Fletcher , Daniel R. Gaya , R Colbert , John Paul Seenan , Jonathan Macdonald , Lucy Lynch , I McLachlan , Stephanie Shields , Richard Hansen , Lisa Gervais , Mwansa Jere , Muhammad Akhtar , Karen Black , Paul Henderson , Richard K. Russell , Charlie W. Lees , Lauranne Derikx , Melanie Lockett , Frederica Betteridge , Aminda De Silva , Arif Hussenbux , John Beckly , Oliver Bendall , J. W. Hart , Amanda Thomas , Benjamin Hamilton , Claire Gordon , Desmond Chee , Timothy J. McDonald , Rachel Nice , Marian Parkinson , Helen Gardner‐Thorpe , Jeff R. Butterworth , Asima Javed , Sarah Al‐Shakhshir , Rekha Yadagiri , Sebrene Maher , Richard Pollok , Tze Pin Ng , Priscilla Appiahene , Fiona Donovan , James Lok , Rajiv Chandy , Reema Jagdish , Daniyal Baig , Zahid Mahmood , Liane Marsh , Allison Moss , Amin Abdulgader , Angus Kitchin , G Walker , Becky George , Yuen‐Hui Lim , James Gulliver , Stuart Bloom , Holly Theaker , Sean Carlson , Fraser Cummings , Robert Livingstone , Amanda Beale , Josiah O. Carter , A. S. Bell , Archibald Coulter , Jonathon Snook , Helen B. Stone , Nicholas A. Kennedy , James Goodhand ·

YOU? · · 2022 · Open Access · · DOI: https://doi.org/10.1111/apt.17170

Summary Background Anti‐drug antibodies are associated with treatment failure to anti‐TNF agents in patients with inflammatory bowel disease (IBD). Aim To assess whether immunogenicity to a patient's first anti‐TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence Methods We conducted a UK‐wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti‐TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti‐TNF agent, defined at any timepoint as an anti‐TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. Results In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27–3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46–4.80, p < 0.001). For each 10‐fold increase in anti‐infliximab and anti‐adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38–2.17, p < 0.001) and 1.99 (95%CI 1.34–2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39–4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti‐TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. Conclusion Irrespective of drug sequence, immunogenicity to the first anti‐TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Related Topics

Medicine

Tumor Necrosis Factor Alpha

Inflammatory Bowel Disease

Disease

Immunology

Internal Medicine

Concepts

Immunogenicity Medicine Tumor necrosis factor alpha Inflammatory bowel disease Disease Inflammatory Bowel Diseases Immunology Antibody Internal medicine

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Type: article
Language: en
Landing Page: https://doi.org/10.1111/apt.17170
PDF: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.17170
OA Status: hybrid
Cited By: 17
References: 34
Related Works: 10
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DOI: https://doi.org/10.1111/apt.17170

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Title: Implications for sequencing of biologic therapy and choice of second anti‐TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti‐TNF therapy (IMSAT) therapeutic drug monitoring study

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Type: article

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Language: en

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Publication year: 2022

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Publication date: 2022-08-29

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Authors: Neil Chanchlani, Simeng Lin, Marcus Auth, Chai Leng Lee, Helena Robbins, Shi Jie Looi, Senthil Murugesan, Tom Riley, Cathryn Preston, Sophie Stephenson, Wendy Cardozo, Sunil Sonwalkar, Mohammed Allah‐Ditta, Lynne Mansfield, Dharmaraj Durai, Mark R. Baker, Ian London, Emily London, Sanjay Gupta, Alex Di Mambro, Aisling Murphy, Edward Gaynor, Kelsey Jones, Andrew Claridge, Shaji Sebastian, Sankaranarayanan Ramachandran, Christian P. Selinger, Simon Borg‐Bartolo, Paul R. Knight, Michael Sprakes, Julie Burton, Patricia Kane, Stephanie Lupton, Aimee Fletcher, Daniel R. Gaya, R Colbert, John Paul Seenan, Jonathan Macdonald, Lucy Lynch, I McLachlan, Stephanie Shields, Richard Hansen, Lisa Gervais, Mwansa Jere, Muhammad Akhtar, Karen Black, Paul Henderson, Richard K. Russell, Charlie W. Lees, Lauranne Derikx, Melanie Lockett, Frederica Betteridge, Aminda De Silva, Arif Hussenbux, John Beckly, Oliver Bendall, J. W. Hart, Amanda Thomas, Benjamin Hamilton, Claire Gordon, Desmond Chee, Timothy J. McDonald, Rachel Nice, Marian Parkinson, Helen Gardner‐Thorpe, Jeff R. Butterworth, Asima Javed, Sarah Al‐Shakhshir, Rekha Yadagiri, Sebrene Maher, Richard Pollok, Tze Pin Ng, Priscilla Appiahene, Fiona Donovan, James Lok, Rajiv Chandy, Reema Jagdish, Daniyal Baig, Zahid Mahmood, Liane Marsh, Allison Moss, Amin Abdulgader, Angus Kitchin, G Walker, Becky George, Yuen‐Hui Lim, James Gulliver, Stuart Bloom, Holly Theaker, Sean Carlson, Fraser Cummings, Robert Livingstone, Amanda Beale, Josiah O. Carter, A. S. Bell, Archibald Coulter, Jonathon Snook, Helen B. Stone, Nicholas A. Kennedy, James Goodhand

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Landing page: https://doi.org/10.1111/apt.17170

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Concepts: Immunogenicity, Medicine, Tumor necrosis factor alpha, Inflammatory bowel disease, Disease, Inflammatory Bowel Diseases, Immunology, Antibody, Internal medicine

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Cited by: 17

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abstract_inverted_index.1.34–2.99,	203
abstract_inverted_index.1.38–2.17,	196
abstract_inverted_index.1.39–4.19,	234
abstract_inverted_index.1.46–4.80,	167
abstract_inverted_index.Irrespective	265
abstract_inverted_index.immunogenic,	259, 294
abstract_inverted_index.inflammatory	15
abstract_inverted_index.introduction	287
abstract_inverted_index.irrespective	38
abstract_inverted_index.multicentre,	47
abstract_inverted_index.subsequently	184
abstract_inverted_index.undetectable	213, 225
abstract_inverted_index.concentration	96
abstract_inverted_index.respectively.	207
abstract_inverted_index.retrospective	48
abstract_inverted_index.concentration,	180
abstract_inverted_index.immunogenicity	23, 34, 55, 82, 154, 161, 211, 223, 269, 278
abstract_inverted_index.immunomodulator	240, 290
abstract_inverted_index.pharmacodynamic	262, 297
abstract_inverted_index.anti‐adalimumab	178
abstract_inverted_index.anti‐infliximab	176
cited_by_percentile_year.max	99
cited_by_percentile_year.min	94
corresponding_author_ids	https://openalex.org/A5082782814
countries_distinct_count	1
institutions_distinct_count	101
corresponding_institution_ids	https://openalex.org/I2799452589
sustainable_development_goals[0].id	https://metadata.un.org/sdg/3
sustainable_development_goals[0].score	0.8399999737739563
sustainable_development_goals[0].display_name	Good health and well-being
citation_normalized_percentile.value	0.92778805
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	True