LAUSR

Since infliximab (IFX), a monoclonal antibody that specifically targets tumor necrosis factor (TNF), is efficacious and safe in the treatment for Crohn’s disease (CD), IFX therapy has become a popular choice for the induction and maintenance of clinical remission [1]. Using biologic drugs in IBD therapy regimens comes with a set of unique challenges, such as avoiding loss of response (LOR), as well as reducing complications from adverse effects (AE), such as infections and malignancy [1, 2]. Furthermore, the development of antibodies to IFX (ATI) is a common cause of LOR and some AEs such as infusion reaction. Although LOR can exacerbate disease, ultimately leading to a switch in therapy [1, 2], CD therapy regimens that use IFX in combination with a thiopurine can reduce the risk of ATI development, improve IFX pharmacokinetics, and increase its efficacy [3], enabling patients with IBD to maintain IFX therapy for longer periods, in addition to reducing IFX infusion reactions. Although the prospective randomized SONIC trial supports the early use of combination therapy, a potential drawback of this regimen is the risk for increased complications, including infections and malignancies such as hepatosplenic T cell lymphoma [4, 5]. Due to this, there is some debate as to whether a thiopurine should be started with IFX or potentially added only if the patient experiences nonresponse. Even though there is literature supporting the efficacy of early combination therapy, there is a lack of studies looking into outcomes after adding a thiopurine in patients already receiving IFX monotherapy who experience primary or secondary nonresponse. Nonetheless, some clinicians and patients may be hesitant to use combination therapy fearing a higher risk of AEs. In this issue of Digestive Disease and Sciences, Zeze et al. [6] report the results of a single-institution retrospective study that compared patients starting combination therapy with IFX and a thiopurine (EC group) to a second cohort of patients receiving IFX monotherapy who commenced thiopurine therapy only after experiencing LOR (LC group). Of the total group of 176 patients with CD, 49 patients were identified as “EC” and 127 patients were identified as “LC” therapy users. Both groups had similar baseline characteristics including demographics and disease phenotype. Assignment was based on each physician’s clinical decision. The primary outcomes of the study were rates of IFX discontinuation and AEs. Though the authors found that rates of IFX continuation were similar between groups, they also found higher rates of AEs in the EC group [6], which parallels results from previous studies [4, 5]. Though this study was retrospective, it suggests that adding a thiopurine “if needed” after developing LOR may be a valid strategy, especially in patients that have a higher risk of developing an AE with combination therapy. The findings could be explained by an improvement in the pharmacokinetic profile of IFX induced due to thiopurine, according to a post hoc analysis of the SONIC trial suggesting that the benefit of combination therapy may be due to an improved pharmacokinetic profile and not to the direct effect of the thiopurine on disease activity [7]. The effects of ATI can be overcome with the addition of an immunomodulator and/ or by increasing the dose of IFX [2]. In this study, the LOR experienced by the LC group could have been explained by the development of ATI, where the addition of a thiopurine could have helped overcome that immunogenicity. It is possible that dose-escalating IFX in patients with LOR would have had the same effect. While briefly mentioned by Zeze et al. [4] systematic measurement of IFX levels and presence of ATI were not recorded in the patients included in this study. The contribution of therapeutic drug monitoring (TDM) to IBD treatment in these patients warrants further investigation. * Andres J. Yarur [email protected]