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 (2022)

Type of publication:Journal article

Author(s):Chanchlani N.; Lin S.; Auth M.K.; Lee C.L.; Robbins H.; Looi S.; Murugesan S.V.; Riley T.; Preston C.; Stephenson S.; Cardozo W.; Sonwalkar S.A.; Allah-Ditta M.; Mansfield L.; Durai D.; Baker M.; London I.; London E.; Gupta S.; Di Mambro A.; Murphy A.; Gaynor E.; Jones K.D.J.; Claridge A.; Sebastian S.; Ramachandran S.; Selinger C.P.; Borg-Bartolo S.P.; Knight P.; Sprakes M.B.; Burton J.; Kane P.; Lupton S.; Fletcher A.; Gaya D.R.; Colbert R.; Seenan J.P.; MacDonald J.; Lynch L.; McLachlan I.; Shields S.; Hansen R.; Gervais L.; Jere M.; Akhtar M.; Black K.; Henderson P.; Russell R.K.; Lees C.W.; Derikx L.A.A.P.; Lockett M.; Betteridge F.; De Silva A.; Hussenbux A.; Beckly J.; Bendall O.; Hart J.W.; Thomas A.; Hamilton B.; Gordon C.; Chee D.; McDonald T.J.; Nice R.; Parkinson M.; Gardner-Thorpe H.; *Butterworth J.R.; *Javed A.; *Al-Shakhshir S.; *Yadagiri R.; *Maher S.; Pollok R.C.G.; Ng T.; Appiahene P.; Donovan F.; Lok J.; Chandy R.; Jagdish R.; Baig D.; Mahmood Z.; Marsh L.; Moss A.; Abdulgader A.; Kitchin A.; Walker G.J.; George B.; Lim Y.-H.; Gulliver J.; Bloom S.; Theaker H.; Carlson S.; Cummings J.R.F.; Livingstone R.; Beale A.; Carter J.O.; Bell A.; Coulter A.; Snook J.; Stone H.; Kennedy N.A.; Goodhand J.R.; Ahmad T.

Citation:Alimentary Pharmacology and Therapeutics, 2022 Oct; Vol. 56 (8), pp. 1250-1263. Date of Publication: October 2022

Abstract:Background: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). <Aim(s): To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to their second, irrespective of drug sequence. <br/>Method(s): 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. Result(s): 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(s): 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.

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DRESS syndrome: an important differential for eosinophilia with systemic organ dysfunction (2020)

Type of publication:
Journal article

*Whoasif Mukit, *Richard Cooper, *Harmesh Moudgil, *Nawaid Ahmad

BMJ Case Reports, 2020 Vol. 13(5)

Drug rash occurring with eosinophilia and systemic symptoms syndrome is a potentially fatal adverse drug reaction that requires immediate action in order to minimise patient harm. Initially implicated with the use of anticonvulsants, it has also been shown to be caused by many other medications but less frequently with vancomycin. Patients typically present with fever, lymphadenopathy, eosinophilia and systemic organ dysfunction. Diagnosis is aided using probability calculators such as RegiSCAR (Registry of Severe Cutaneous Adverse Reaction), as well as clinical response on removing the responsible medication. Here, we present a case without any systemic organ dysfunction that improved with withdrawal of the offending drug vancomycin.

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