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
Authors: Chanchlani Neil , Lin Simeng , Auth Marcus K. , Lee Chai Leng , Robbins Helena , Looi Shi , Murugesan Senthil V. , Riley Tom , Preston Cathryn , Stephenson Sophie , Cardozo Wendy , Sonwalkar Sunil A. , Allah‐Ditta Mohammed , Mansfield Lynne , Durai Dharmaraj , Baker Mark , London Ian , London Emily , Gupta Sanjay , Di Mambro Alex , Murphy Aisling , Gaynor Edward , Jones Kelsey D. J. , Claridge Andrew , Sebastian Shaji , Ramachandran Sankaranarayanan , Selinger Christian P. , Borg‐Bartolo Simon P. , Knight Paul , Sprakes Michael B. , Burton Julie , Kane Patricia , Lupton Stephanie , Fletcher Aimee , Gaya Daniel R. , Colbert Roghan , Seenan John Paul , MacDonald Jonathan , Lynch Lucy , McLachlan Iain , Shields Stephanie , Hansen Richard , Gervais Lisa , Jere Mwansa , Akhtar Muhammad , Black Karen , Henderson Paul , Russell Richard K. , Lees Charlie W. , Derikx Lauranne A. A. P. , Lockett Melanie , Betteridge Frederica , De Silva Aminda , Hussenbux Arif , Beckly John , Bendall Oliver , Hart James W. , Thomas Amanda , Hamilton Ben , Gordon Claire , Chee Desmond , McDonald Timothy J. , Nice Rachel , Parkinson Marian , Gardner‐Thorpe Helen , Butterworth Jeff R. , Javed Asima , Al‐Shakhshir Sarah , Yadagiri Rekha , Maher Sebrene , Pollok Richard C. G. , Ng Tze , Appiahene Priscilla , Donovan Fiona , Lok James , Chandy Rajiv , Jagdish Reema , Baig Daniyal , Mahmood Zahid , Marsh Liane , Moss Allison , Abdulgader Amin , Kitchin Angus , Walker Gareth J. , George Becky , Lim Yuen‐Hui , Gulliver James , Bloom Stuart , Theaker Holly , Carlson Sean , Cummings J. R. Fraser , Livingstone Robert , Beale Amanda , Carter Josiah O. , Bell Andrew , Coulter Archibald , Snook Jonathon , Stone Helen , Kennedy Nicholas A. , Goodhand James R. , Ahmad Tariq ,   IMSAT study investigators
Published: August 2022

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.