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

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

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Abstract

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.
Original languageEnglish
Pages (from-to)1250-1263
Number of pages14
JournalAlimentary Pharmacology & Therapeutics
Volume56
Issue number8
Early online date29 Aug 2022
DOIs
Publication statusPublished - 27 Sept 2022

Keywords

  • Adalimumab/therapeutic use
  • Antibodies
  • Biological Therapy
  • Drug Monitoring
  • Humans
  • Immunologic Factors/therapeutic use
  • Inflammatory Bowel Diseases/drug therapy
  • Infliximab/therapeutic use
  • Retrospective Studies
  • Tumor Necrosis Factor Inhibitors/therapeutic use
  • Tumor Necrosis Factor-alpha

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