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.
adalimumab
anti-TNF
antibodies
drug persistence
immunogenicity
infliximab
therapeutic drug monitoring
treatment failure
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
05
07
2022
received:
05
06
2022
accepted:
19
07
2022
pubmed:
31
8
2022
medline:
30
9
2022
entrez:
30
8
2022
Statut:
ppublish
Résumé
Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36039036
doi: 10.1111/apt.17170
pmc: PMC9804266
doi:
Substances chimiques
Antibodies
0
Immunologic Factors
0
Tumor Necrosis Factor Inhibitors
0
Tumor Necrosis Factor-alpha
0
Infliximab
B72HH48FLU
Adalimumab
FYS6T7F842
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1250-1263Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S034919/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222850/Z/21/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Références
Expert Rev Gastroenterol Hepatol. 2018 Aug;12(8):797-810
pubmed: 29957083
N Engl J Med. 2010 Apr 15;362(15):1383-95
pubmed: 20393175
Cancer. 1950 Jan;3(1):32-5
pubmed: 15405679
Lancet Gastroenterol Hepatol. 2019 May;4(5):341-353
pubmed: 30824404
Arthritis Res Ther. 2013 Jul 26;15(4):R79
pubmed: 23890223
Gut. 2018 May;67(5):818-826
pubmed: 28450388
Gut. 2020 Jul;69(7):1206-1212
pubmed: 31980448
Gastroenterology. 2015 Jun;148(7):1320-9.e3
pubmed: 25724455
Value Health. 2008 Jan-Feb;11(1):44-7
pubmed: 18237359
Clin Gastroenterol Hepatol. 2022 Feb;20(2):465-467.e2
pubmed: 33421628
Aliment Pharmacol Ther. 2022 Oct;56(8):1250-1263
pubmed: 36039036
Gastroenterology. 2020 Jan;158(1):189-199
pubmed: 31600487
Aliment Pharmacol Ther. 2020 Mar;51(6):612-628
pubmed: 31961001
Aliment Pharmacol Ther. 2017 Nov;46(9):873-882
pubmed: 28884856
Aliment Pharmacol Ther. 2016 Jan;43(1):30-51
pubmed: 26515897
MAbs. 2015;7(4):662-71
pubmed: 25962087
Aliment Pharmacol Ther. 2020 Feb;51(3):356-363
pubmed: 31650614
Aliment Pharmacol Ther. 2013 Jun;37(12):1172-83
pubmed: 23650912
Inflamm Bowel Dis. 2018 Aug 16;24(9):2078-2085
pubmed: 29718216
Lancet Gastroenterol Hepatol. 2022 Feb;7(2):171-185
pubmed: 35026171
Aliment Pharmacol Ther. 2021 Jan;53(1):128-137
pubmed: 33226651
Inflamm Bowel Dis. 2020 Mar 4;26(4):606-616
pubmed: 31504569
Am J Gastroenterol. 2014 Aug;109(8):1250-6
pubmed: 24913041
Aliment Pharmacol Ther. 2015 Apr;41(7):613-23
pubmed: 25652884
Ann Rheum Dis. 2010 May;69(5):817-21
pubmed: 19581278
Therap Adv Gastroenterol. 2018 Jan 21;11:1756283X17750355
pubmed: 29383030
Aliment Pharmacol Ther. 2017 Jan;45(2):276-282
pubmed: 27862102
Am J Gastroenterol. 2018 Jun;113(6):890-898
pubmed: 29867175
J Biomed Inform. 2019 Jul;95:103208
pubmed: 31078660
Inflamm Bowel Dis. 2014 Oct;20(10):1714-21
pubmed: 25069030
Ann Rheum Dis. 2015 Jan;74(1):311-4
pubmed: 25342759