This may explain some of the differences in immunogenicity rates between RA and other diseases, where these cytokines are thought to be less important

This may explain some of the differences in immunogenicity rates between RA and other diseases, where these cytokines are thought to be less important. Our study identified risk factors for ADAb formation in patients treated with infliximab, and further research should address whether these risk factors are also of significance in patients treated with less immunogenic TNFi. ADAb in the early phase of infliximab treatment. Methods CLC Patients (= 410) with immune\mediated inflammatory diseases who initiated infliximab treatment were included in the 38\week Norwegian Drug Monitoring Trial (NOR\DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders. Results ADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0C3.6]) and lifetime smoking (OR, 2.0 [CI 1.1C3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2C0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2C0.8]) reduced the risk of ADAb. Higher disease activity during follow\up (OR, 1.1 [CI 1.0C1.1]) and drug holidays of more than 11?weeks (OR, 4.1 [CI 1.2C13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0C0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6C0.8]) reduced the risk of immunogenicity. Conclusion Several risk factors for ADAb formation during early\phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these steps are of particular importance. Keywords: autoimmune disease, immunosuppressive treatment ??? Introduction Tumour necrosis factor inhibitors (TNFi), including infliximab, have revolutionised the treatment of prevalent chronic immune\mediated inflammatory diseases such as rheumatoid arthritis (RA), psoriatic KC01 arthritis (PsA), spondyloarthritis (SpA), ulcerative colitis (UC), Crohn’s disease (CD), and psoriasis (Ps). However, lack or loss of response to treatment, leading to increased disability, reduced quality of life, and potential irreversible organ damage, is seen in up to 55% of patients during the first 6 months of treatment [1, 2, 3, 4]. Immunogenicity is usually a major concern associated with TNFi use. The formation of neutralising anti\drug antibodies (ADAb) which inactivate the therapeutic agent is usually a leading cause of TNFi treatment failure [5, 6, 7, 8, 9]. ADAb formation is also related to security issues and frequently prospects to infusion reactions in patients on infliximab therapy [5, 10, 11]. Immunogenicity is usually of particular concern early in the treatment course [12]. Infliximab, a murine\human chimeric antibody, exhibits a greater immunogenic potential than other TNFi, and ADAb eventually develop in approximately one out of four patients [7]. Data to help identify patients at risk of developing ADAb are scarce. The use of concomitant immunosuppressive medications, such as methotrexate and azathioprine, has been suggested to prevent ADAb formation [7, 13] whereas smoking and prior use of TNFi may increase the risk of ADAb formation [14, 15]. Low serum infliximab KC01 concentrations have been proposed to trigger KC01 immunogenicity [16], but a slice\off associated with this increased risk has not yet been recognized. Studies examining risk factors and mitigation strategies across disease groups are lacking. The Norwegian Drug Monitoring Trial (NOR\DRUM) A randomised clinical trial assessed the effectiveness of proactive therapeutic drug monitoring (TDM) during induction of infliximab therapy and did not find TDM to be superior to standard infliximab therapy in terms of achieving clinical remission in the overall population [17]. However, the subgroup of patients who subsequently developed ADAb benefited from TDM during induction therapy, suggesting that TDM might be a beneficial treatment strategy in patients at increased risk of immunogenicity [18]. Identifying patients at risk of ADAb formation is usually clinically important for the timely detection of ADAb to prevent treatment failure and immunogenicity\related side effects. Increased knowledge of risk factors will facilitate the choice of treatment strategies to mitigate the formation of ADAb. The aim of this sub\study of the KC01 NOR\DRUM A trial [17] was to identify individual\ and treatment\related risk factors for ADAb formation, including the relationship between infliximab serum concentrations.