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 naive Patients in Crohn’s Disease (SONIC) randomised controlled trial (RCT) showed that combination therapy with azathioprine appears to …

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硫唑嘌呤在 IBD 中转换抗 TNFs 的新作用

抗肿瘤坏死因子 (anti-TNF) 治疗彻底改变了中度至重度炎症性肠病 (IBD) 的治疗。然而，多达 30% 的克罗恩病 (CD) 和溃疡性结肠炎 (UC) 患者对抗 TNF 治疗没有反应，通常称为原发性无反应者。此外，几乎 50% 最初对抗 TNF 有反应的患者随着时间的推移失去反应，这种现象称为继发性反应丧失 (SLR)。 1 这两种负面结果最常见的原因是药代动力学问题，其特征是无法检测到或低药物由于存在或不存在抗药抗体 (ADA) 的情况下清除率增加而导致浓度增加，即所谓的免疫原性。2 最近的前瞻性克罗恩病研究中的个性化抗 TNF 治疗 (PANTS) 研究表明，对于英夫利昔单抗和阿达木单抗，