Efficacy and Safety of Ustekinumab in Treatment of Ulcerative Colitis: A Systematic Review

Ulcerative colitis (UC) is a chronic, relapsing, and remitting immune-mediated condition requiring long-term therapy. Moderate to severe disease is managed using steroids, sulfasalazine, thiopurines, biologicals [anti-tumor necrosis factor, anti-integrins, and anti-interleukin (IL) 12/23], and small molecules (janus kinase inhibitors, sphingosine-1-receptor modulators). Ustekinumab (UST) is an IgG1 monoclonal antibody acting on IL 12/23 recently authorized to treat moderate to severe UC that is not responsive to other biologic medicines. There remains an unmet need in the management of UC despite the growing availability of therapeutic agents. Current treatment algorithms use a standard approach for all patients, but targeted therapies are required for better outcomes. This systematic review aims to evaluate the safety and efficacy of UST in patients with moderate to severe UC. We also noted the clinical and endoscopic improvement with maintenance of clinical and steroid-free remission across multiple databases to strengthen reproducibility. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) 2020 guidelines. Relevant literature was retrieved from PubMed, PubMed Central, Cochrane Library, Science Direct, and Google Scholar. Articles published in English within the last five years (2020 to 2025) were included. Quality assessment tools were applied to ensure the quality of evidence-based medicine that will be utilized to develop a conclusion and direct future review. The studies analysed showed a superiority of UST in the induction and maintenance of remission in active, difficult-to-treat UC. Our findings indicate that a reduction in Mayo score with improvement in c-reactive protein (CRP) and fecal calprotectin (fCal) can be used to assess a reduction in inflammatory burden and response to treatment. Histo-endoscopic mucosal healing also provides a long-term clinical assessment of the reduction in disease burden. All safety events that led to drug discontinuation and malignancy were similar for UST therapy and placebo. UST, as a treatment option for moderate to severe UC, can provide an alternative avenue in the development of patient-centric targeted therapies. Further research targets should include the formulation of a standard dosing regimen and the evaluation of the long-term safety profile of the drug. There is also limited literature available for comparative analysis of UST treatment with other available therapeutic options, especially biologic agents, and its effect on extra-intestinal manifestations.