Real-World Effectiveness and Safety of Ustekinumab in Patients With Ulcerative Colitis

Carlos Taxonera; David Olivares; Olga N. López-García; Cristina Alba


Aliment Pharmacol Ther. 2023;57(6):610-619. 

In This Article

Abstract and Introduction


Background: Evidence on real-world outcomes of ustekinumab for ulcerative colitis (UC) patients is needed.

Aims: To summarise evidence on the real-world outcomes of ustekinumab for UC and conduct a meta-analysis of effectiveness and safety data.

Methods: A systematic search was conducted through September 2022 in electronic databases for observational studies evaluating ustekinumab for UC. A random-effects meta-analysis model was used to calculate the pooled effect sizes (percentages or incidence rates [IRs]) of effectiveness and safety outcomes.

Results: In all, 19 studies were included with 3786 patients. More than 92% of patients were previously treated with any biologic, 61.1% with both anti-TNF and vedolizumab and 16.4% with any biologic and tofacitinib. Clinical remission was achieved in 45.4% at week 8 (95% CI: 30.1%–60.6%), 43.8% (38.4%–49.2%) at weeks 12–16, 44.6% (35.9%–53.3%) at month 6, and 50.6% (36.3%–64.8%) at month 12. Response was achieved in 61.2%, 59.4%, 65.2% and 76.8% at weeks 8, 12–16, month 6 and 12, respectively. CS-free remission was achieved in 18.7%, 36.8%, 34.5% and 39% at weeks 8, 12–16, month 6 and 12, respectively. Overall, 58.2% of patients had endoscopic improvement at month 12. Almost 30% of the patients needed dose escalation, which was effective in 40% of these patients. The IRs of colectomy, adverse events (AEs), serious AEs and serious infections were 4.8, 7.9, 0.8 and 0.3 per 100 patient-years, respectively.

Conclusions: This meta-analysis confirms the effectiveness and safety of ustekinumab in a highly treatment-refractory population of UC patients.


Ustekinumab is a fully human monoclonal IgG1 kappa antibody targeting the interleukin (IL)-12 and IL-23 shared p40 subunit. Based on the efficacy and safety shown in the UNITI trials, ustekinumab obtained approval in 2016 for Crohn's disease (CD).[1] Subsequently, following the results of the Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UNIFI), ustekinumab was approved in 2019 for ulcerative colitis (UC) patients.[2] The UNIFI clinical trial showed that in patients with moderate-to-severely active UC despite current or previous treatment with conventional or biologic therapy, intravenous ustekinumab was more effective than placebo in achieving induction of clinical remission at 8 weeks.[2] The maintenance trial showed the efficacy of subcutaneous treatment every 8 or 12 weeks to week 52 for those who responded in the induction trial.[2] In addition, ustekinumab was also able to induce endoscopic and histologic remission in patients with UC.[3]

Strict inclusion criteria used in randomised controlled trials (RCTs) can limit the patient population and generalisability of trial results to clinical practice. This issue has been shown to be particularly relevant in inflammatory bowel disease (IBD) populations.[4] Therefore, studies evaluating effectiveness in the real-world setting are relevant to provide generalisable clinical efficacy that confirm results reported by RCTs and to guide therapeutic decisions. Currently, gastroenterologists have several personalised treatment options suitable for moderate-to-severe UC, including three TNF-α antibodies, ustekinumab, vedolizumab, belonging to the anti-integrin class, and tofacitinib and filgotinib from the superfamily of JAK inhibitors. Given this wide range of therapeutic options available, it is of particular interest to assess the real-world effectiveness and safety of ustekinumab to enable patients and clinicians to make an informed decision. In this scenario, in the last few years, several observational studies evaluating outcomes of ustekinumab in UC have been conducted.[5–9] A meta-analysis can enhance the robustness of reported observations.

The aim of this systematic review was to summarise reported evidence on the real-world outcomes of ustekinumab for UC and to conduct a meta-analysis of effectiveness and safety data.