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. 2022 Oct;56(8):1250-1263.
doi: 10.1111/apt.17170. Epub 2022 Aug 29.

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  1 , Simeng Lin  1 , Marcus K Auth  2 , Chai Leng Lee  2 , Helena Robbins  3 , Shi Looi  3 , Senthil V Murugesan  4 , Tom Riley  4 , Cathryn Preston  5 , Sophie Stephenson  5 , Wendy Cardozo  5 , Sunil A Sonwalkar  6 , Mohammed Allah-Ditta  6 , Lynne Mansfield  6 , Dharmaraj Durai  7 , Mark Baker  7 , Ian London  8 , Emily London  8 , Sanjay Gupta  9 , Alex Di Mambro  10 , Aisling Murphy  10 , Edward Gaynor  11 , Kelsey D J Jones  11 , Andrew Claridge  12 , Shaji Sebastian  13 , Sankaranarayanan Ramachandran  13 , Christian P Selinger  14 , Simon P Borg-Bartolo  15 , Paul Knight  15 , Michael B Sprakes  16 , Julie Burton  16 , Patricia Kane  16 , Stephanie Lupton  16 , Aimee Fletcher  16 , Daniel R Gaya  17 , Roghan Colbert  17 , John Paul Seenan  18 , Jonathan MacDonald  18 , Lucy Lynch  18 , Iain McLachlan  18 , Stephanie Shields  18 , Richard Hansen  19 , Lisa Gervais  19 , Mwansa Jere  19 , Muhammad Akhtar  20 , Karen Black  20 , Paul Henderson  21 , Richard K Russell  21 , Charlie W Lees  22 , Lauranne A A P Derikx  22 , Melanie Lockett  23 , Frederica Betteridge  23 , Aminda De Silva  24 , Arif Hussenbux  24 , John Beckly  25 , Oliver Bendall  25 , James W Hart  1 , Amanda Thomas  1 , Ben Hamilton  1 , Claire Gordon  1 , Desmond Chee  1 , Timothy J McDonald  1 , Rachel Nice  1 , Marian Parkinson  1 , Helen Gardner-Thorpe  1 , Jeff R Butterworth  26 , Asima Javed  26 , Sarah Al-Shakhshir  26 , Rekha Yadagiri  26 , Sebrene Maher  26 , Richard C G Pollok  27 , Tze Ng  27 , Priscilla Appiahene  27 , Fiona Donovan  27 , James Lok  27 , Rajiv Chandy  28 , Reema Jagdish  28 , Daniyal Baig  28 , Zahid Mahmood  29 , Liane Marsh  29 , Allison Moss  30 , Amin Abdulgader  30 , Angus Kitchin  30 , Gareth J Walker  31 , Becky George  31 , Yuen-Hui Lim  31 , James Gulliver  31 , Stuart Bloom  32 , Holly Theaker  32 , Sean Carlson  32 , J R Fraser Cummings  33 , Robert Livingstone  33 , Amanda Beale  34 , Josiah O Carter  34 , Andrew Bell  35 , Archibald Coulter  35 , Jonathon Snook  36 , Helen Stone  36 , Nicholas A Kennedy  1 , James R Goodhand  1 , Tariq Ahmad  1 ; IMSAT study investigators
Affiliations

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 et al. Aliment Pharmacol Ther. 2022 Oct.

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.

Keywords: adalimumab; anti-TNF; antibodies; drug persistence; immunogenicity; infliximab; therapeutic drug monitoring; treatment failure.

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Conflict of interest statement

Neil Chanchlani has nothing to declare. Simeng Lin reports non‐financial support from Pfizer and Ferring, outside the submitted work. Nicholas A Kennedy reports grants from F. Hoffmann‐La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV and non‐financial support from Immundiagnostik, during the conduct of the study; grants and non‐financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non‐financial support from Janssen, personal fees from Takeda, personal fees and non‐financial support from Dr Falk, outside the submitted work. James R Goodhand reports grants from F. Hoffmann‐La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV and non‐financial support from Immundiagnostik, during the conduct of the study. Tariq Ahmad reports grants and non‐financial support from F. Hoffmann‐La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV and non‐financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen inc, grants and personal fees from Celltrion Healthcare, personal fees and non‐financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non‐financial support from Tillotts, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Patient disposition.
FIGURE 2
FIGURE 2
Forest plot showing the coefficients from a multivariable logistic regression model of associations with immunogenicity to first anti‐TNF.
FIGURE 3
FIGURE 3
Risk of immunogenicity to second anti‐TNF, stratified by immunogenicity to first anti‐TNF.
FIGURE 4
FIGURE 4
Drug persistence to second anti‐TNF, stratified by first anti‐TNF and type of failure to first anti‐TNF.
FIGURE 5
FIGURE 5
Drug persistence to second anti‐TNF, stratified by treatment failure to first anti‐TNF and immunomodulator status with second anti‐TNF.
See this image and copyright information in PMC

Comment in

References

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