TY - JOUR
T1 - Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease
T2 - results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study
AU - Chanchlani, Neil
AU - Lin, Simeng
AU - IMSAT study investigators
AU - Auth, Marcus K.
AU - Lee, Chai Leng
AU - Robbins, Helena
AU - Looi, Shi
AU - Murugesan, Senthil V.
AU - Riley, Tom
AU - Preston, Cathryn
AU - Stephenson, Sophie
AU - Cardozo, Wendy
AU - Sonwalkar, Sunil A.
AU - Allah-Ditta, Mohammed
AU - Mansfield, Lynne
AU - Durai, Dharmaraj
AU - Baker, Mark
AU - London, Ian
AU - London, Emily
AU - Gupta, Sanjay
AU - Di Mambro, Alex
AU - Murphy, Aisling
AU - Gaynor, Edward
AU - Jones, Kelsey D.J.
AU - Claridge, Andrew
AU - Sebastian, Shaji
AU - Ramachandran, Sankaranarayanan
AU - Selinger, Christian P.
AU - Borg-Bartolo, Simon P.
AU - Knight, Paul
AU - Sprakes, Michael B.
AU - Burton, Julie
AU - Kane, Patricia
AU - Lupton, Stephanie
AU - Fletcher, Aimee
AU - Gaya, Daniel R.
AU - Colbert, Roghan
AU - Seenan, John Paul
AU - MacDonald, Jonathan
AU - Lynch, Lucy
AU - McLachlan, Iain
AU - Shields, Stephanie
AU - Hansen, Richard
AU - Gervais, Lisa
AU - Jere, Mwansa
AU - Akhtar, Muhammad
AU - Black, Karen
AU - Henderson, Paul
AU - Russell, Richard K.
AU - Lees, Charlie W.
AU - Derikx, Lauranne A.A.P.
AU - Goodhand, James R.
AU - Ahmad, Tariq
N1 - Publisher Copyright: © 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85136885612
U2 - 10.1111/apt.17170
DO - 10.1111/apt.17170
M3 - Article
C2 - 36039036
AN - SCOPUS:85136885612
SN - 0269-2813
VL - 56
SP - 1250
EP - 1263
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 8
ER -