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Antitumour necrosis factor (anti-TNF) therapy has revolutionised the treatment of moderate to severe inflammatory bowel disease (IBD). However, up to 30% of patients with Crohn’s disease (CD) and ulcerative colitis (UC) do not respond to anti-TNF therapy, often referred to as primary non-responders. Additionally, almost 50% of patients who initially respond to anti-TNF lose response over time, a phenomenon known as secondary loss of response (SLR).1 Both of these negative outcomes are most commonly caused by pharmacokinetic issues characterised by undetectable or low drug concentrations due to increased clearance with or without the presence of antidrug antibodies (ADA), so-called immunogenicity.2 The recent prospective The Personalised Anti-TNF therapy in Crohn’s Disease Study (PANTS) study showed that for both infliximab and adalimumab, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of ADA predicted subsequent low drug concentrations.3 Immunogenicity may account for at least 20% of SLR in patients with IBD.2
The addition of an immunomodulator (IMM), such as a thiopurine or methotrexate, has been shown to improve the pharmacokinetic profile of anti-TNF agents both by attenuating immunogenicity and increasing drug concentrations.3–5 These factors consequently lead to better long-term clinical outcomes and less SLR.3–5 A post hoc analysis of the Study of Biologic and Immunomodulator naïve Patients in Crohn’s Disease (SONIC) randomised controlled trial (RCT) showed that combination therapy with azathioprine appears to …
Contributors KP: drafting and final approval of the manuscript; ASC: critical revision and final approval of the manuscript. PMI: critical revision and final approval of the manuscript.
Funding KP: Ruth L. Kirschstein NRSA Institutional Research Training Grant (5T32DK007760-18).
Competing interests KP: received a lecture fee from Mitsubishi Tanabe Pharma; ASC: received consultancy fees from AbbVie, Janssen, Takeda, Miraca, Ferring, AMAG and Pfizer; PMI has received honoraria for acting in an advisory capacity for or talking on behalf of AbbVie, Arena, Celgene, Falk Pharma, Ferring, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Prometheus, Roche, Takeda, Tillotts, Topivert, Sapphire Medical, Sandoz, Shire, VH2, Vifor Pharma, Warner Chilcott, and has received research support from MSD, Takeda and Pfizer.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.