Chanchlani, N;
Lin, S;
Auth, MK;
Lee, CL;
Robbins, H;
Looi, S;
Murugesan, SV;
... Goodhand, JR; + view all
(2022)
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.
Alimentary Pharmacology and Therapeutics
10.1111/apt.17170.
(In press).
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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 their 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 drug, 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 anti-TNF, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.
| Type: | Article |
|---|---|
| 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 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/apt.17170 |
| Publisher version: | https://doi.org/10.1111/apt.17170 |
| Language: | English |
| Additional information: | © 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | adalimumab, anti-TNF, antibodies, drug persistence, immunogenicity, infliximab, therapeutic drug monitoring, treatment failure |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10155718 |
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