Editorial: Effectiveness and safety of ustekinumab in ulcerative colitis—Where we are now in real life

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon. Because of its relapsing and remitting course, it sometimes requires an aggressive therapeutic approach to prevent complications.^{1, 2}

Ustekinumab is a humanised monoclonal IgG₁ kappa antibody blocking the p40 subunit of the interleukins (IL) 12/23.³ It was approved by the European Medicines Agency in September 2019⁴ for the treatment of moderate to severe UC after the UNIFI study had demonstrated its efficacy and safety.⁵ In recent years, ‘real-world’ data have confirmed its effectiveness and safety.⁶ However, the latter studies have been limited by small population samples enrolled and short follow-up.

Chaparro et al.⁷ have analysed retrospective data from a Spanish multicentre cohort and reported short- and long-term outcomes in patients with UC treated with ustekinumab. There were four key findings from this study.

First, there was a large number of patients enrolled (620), with fairly good length of follow-up, for the long-term evaluation of drug safety. Second, only 25% discontinued ustekinumab during follow-up, with a discontinuation incidence rate of 20% per patient-year. This was very interesting, especially because it concerned a multi-refractory cohort, composed almost entirely of bio-experienced patients who had failed an average of two biologic treatments. Third, the primary effectiveness endpoint of steroid-free clinical remission at week 16 was reached by 40% of patients. This was lower than in the UNIFI trial⁵ (58.4% and 53% in patients treated with ustekinumab 130 mg iv and with 6 mg/kg iv, respectively). In UNIFI, symptomatic remission could be with or without steroids, in line with the real-life data published so far, in which steroid-free remission after 4–16 weeks ranged from 14% to 67%.⁶ To give more strength to the data in the analysis of short-term efficacy, the authors only considered patients who had active disease at baseline. Furthermore, looking at long-term effectiveness, 75% and 57% of patients in remission at week 16 maintained steroid-free clinical remission at 12 and 24 months, respectively. Fourth, this study confirmed an excellent safety profile of ustekinumab for UC in routine clinical practice, since only 12 and 7 patients out of 620 had to temporarily or permanently suspend treatment.

However, there are some limitations to consider. The main limitation was the retrospective, uncontrolled design. Furthermore, clinical remission—the primary effectiveness endpoint—was defined as a PMS ≤2, while other studies defined it as PMS ≤1.⁸ This means that patients with few symptoms could be considered ‘in remission’.⁷ Another limitation was the lack of endoscopic data during follow-up, which was reported by other studies performed in the same setting.^{8, 9}

Overall, this study, together with other recent large real life-studies (Table 1), supports the benefit of ustekinumab in real-world practice during long-term follow-up.^7-10

Giammarco Mocci: Conceptualization; writing – original draft; methodology; validation; formal analysis; writing – review and editing; data curation. Antonio Tursi: Conceptualization; writing – original draft; methodology; validation; writing – review and editing; supervision; data curation.

Giammarco Mocci served as speaker and/or advisory board fees for AbbVie, Amgen, Aurora Biopharma, Biogen, Celltrion, Chiesi, Fenix Pharma, Ferring, Galápagos, Janssen, MSD, Omega Pharma, Sandoz, Takeda and Vifor Pharma; Antonio Tursi served as speaker and/or consultant for AbbVie, Bayer, Fenix Pharma, Galápagos, Janssen, Nalkein and Omega Pharma.

This article is linked to Chaparro et al papers. To view these articles, visit https://doi.org/10.1111/apt.18230 and https://doi.org/10.1111/apt.18316