Ustekinumab in ulcerative colitis- insights from the real-world data.

The therapeutic arsenal for ulcerative colitis (UC) has increasingly expanded over the past years, along with improved comprehension of the pathogenesis and identification of key cytokines promoting bowel inflammation. Interleukin (IL) −12 and IL23 are two key cytokines in the pathogenesis of intestinal inflammation. IL12 promotes the differentiation of naïve T cells in Th1 effectors, while IL23 exerts its effect by perpetrating the pro‐inflammatory functions of Th17 cells. , Ustekinumab is a humanised monoclonal igG1 kappa antibody directed against the common P40 subunit of interleukin‐12 and interleukin‐23. It was first approved in 2019 as treatment for moderate to severe UC following the UNIFI study, which demonstrated its efficacy and safety. Since then, several studies evaluate ustekinumab efficacy among UC patients, including patients with refractory disease. Ochsenkühn et al. described the efficacy and safety of ustekinumab in refractory UC patients with a history of multiple biological therapies. In pediatric population, Dhaliwal and colleagues reported the efficacy of ustekinumab in pediatric anti‐TNF experienced patients.

In their study “Real‐world outcomes of ustekinumab treatment in ulcerative colitis: results from the Swedish Inflammatory Bowel Disease Quality Register” Thunberg and colleagues analyzed prospective data from the Swedish Inflammatory Bowel Disease quality Register (SWIBREG), and reported the short‐ and long‐term outcomes in UC patients treated with ustekinumab. In this study, which included 133 patients, the primary outcome of ustekinumab persistence rate at 16 weeks was 86%, and 67% after a median follow‐up of 32 weeks. It should be mentioned that only three patients were naïve to biologics and tofacitinib in this study. The persistence rate reported here is lower than reported in the UNIFI maintenance study, however, the latter included only patients who responded to the induction therapy. Recent studies among Crohn's disease patients treated with ustekinumab demonstrated comparable persistent rates comparable to those reported by Thunberg and colleagues. , ,

In accordance to previously published real‐world data, ustekinumab treatment was associated with improvements in clinical biochemical parameters. In addition, this is the first real‐world experience study to report the effect of ustekinumab treatment on health‐related quality of life in UC. Importantly, the effect was demonstrated in a highly resistant population, with the majority of patients failing at least 2 previous biologics or small molecules.

As duly noted by the authors, the main limitations of the study system form retrospective non‐controlled design. Importantly, the primary outcome of the study was treatment persistence and not clinical efficacy, and this as early as 16 weeks (correlating to 3rd treatment in most cases). Data on clinical outcomes was missing in a large proportion of the patients.

Given the variety of available treatments, clinicians may face difficulty in when and in what order to position different drugs. Although randomized clinical trials are considered as “gold standard” for the evaluation of efficacy and safety of new therapies, they usually required strict inclusion and exclusion criteria leading to a study population that might not properly embody the patient populations encountered in clinical practice. On the other hand, real‐world studies utilize large datasets across diverse populations, including those forgone by clinical trials, and pragmatic clinical outcomes, providing complimentary post marketing data that may assist in positioning and sequencing of the available therapeutic agents.

The future of IBD management is expected to evolve in the upcoming years with the introduction of additional and novel treatment options. While this evolution has a great potential for improving IBD care, the physicians will face a significant challenge in tailoring the right treatment to each patient. Real world studies assessing treatment efficacy, safety and treatment persistence provide crucial pieces for the solution of the treatment sequencing puzzle.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare. Uri Kopylov received speaker and advisory fees from Abbvie BMS Jannsen Takeda Pfizer Sandoz/Novartis Medtronic; and research support from Jannsen Takeda Medtronic.