In Brief | Autoimmune Diseases | Ulcerative Colitis
Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies
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Originally Published: 4 January 2026
Sourced: Lancet
Type of article: In Brief
MedED Catalogue Reference: MAIB002
Category: Autoimmune Diseases
Cross Reference: Paediatrics, Gastroenterology
Keywords: inflammatory bowel diseases, Chron's disease, ulcerative colitis, biologics, gastroenterology
Guselkumab demonstrates significant efficacy in inducing and maintaining clinical remission in UC, with a favourable safety profile, including no reports of serious complications, highlighting its potential as a viable treatment option.
This article is a review of recent studies originally published in the Lancet, 4 January 2025. It does not represent the original research, nor is it intended to replace the original research. Access the full Disclaimer Information.
Ulcerative colitis (UC) and Crohn's disease are chronic inflammatory bowel diseases (IBD) that carry a significant morbidity burden for their sufferers. While their exact aetiology remains unclear, they are thought to result from immune system dysregulation in response to the gut microbiota in genetically susceptible individuals, a process referred to as the loss of oral tolerance.
The goal of medical treatment for IBD is to rapidly induce steroid-free remission while preventing complications both from the disease itself and its treatment. Treatment decisions depend on the severity, location, and progression of the disease. Conventional therapies include mesalamine, corticosteroids, and thiopurines, as well as biological therapies (such as anti-cytokines and anti-integrins) and JAK inhibitors like tofacitinib.2,4
Interleukin-23 (IL-23) has been identified as a key player in UC pathogenesis. Elevated levels of IL-23 and T-helper (Th) 17 cell cytokines have been found in the intestinal mucosa, plasma, and serum of patients with IBD, and blocking IL-23 has been shown to reduce inflammation in experimental colitis models.1
Guselkumab, a human IgG1 IL-23p19 subunit inhibitor, neutralises IL-23 and binds to CD64. Currently licensed in South Africa under the trademark Tremfeya™ for the treatment of psoriasis, guselkumab shows promise as a potential therapy for UC, offering a targeted approach to modulating immune responses in IBD patients.
Study Purpose
This study aimed to evaluate the efficacy and safety of guselkumab as both induction and maintenance therapy in patients with moderately to severely active UC who had inadequate responses or intolerance to conventional or advanced therapies.
Study Methodology
The research involved two phase 3 randomised, double-blind, placebo-controlled trials: the QUASAR phase 3 induction and maintenance studies.
Induction Study
701 patients with a baseline modified Mayo score of 5–9 were randomised (3:2) to receive either guselkumab 200 mg intravenously or placebo at weeks 0, 4, and 8.
Maintenance Study
Induction responders (n=568) were randomised (1:1:1) to receive subcutaneous guselkumab 200 mg every 4 weeks, 100 mg every 8 weeks, or placebo for 44 weeks.
The primary endpoints were clinical remission at induction week 12 and maintenance week 44.
Findings
Induction Phase
23% (95/421) of the patients receiving guselkumab demonstrated clinical remission at week 12
In contrast 8% of placebo-treated patients (22/280) at the same time frame. (adjusted treatment difference 15%; 95% CI 10–20; p<0.0001).
Maintenance Phase
Clinical remission at week 44 was higher in guselkumab-treated patients: Specifically, remission was determined in 50% (95\190) of patients treated with 200mg subcut every day ( AD 30%) and 45% (85/188) of those treated with with 100 mg every 8 weeks (AD 25%.) In the placebo group, remission was determined in 19% of the patients (36/190).
Safety
Adverse Events were reported by 49% of patients in both groups, with serious adverse events reported in the guselkumab-treated patients (3%) than the placebo patients (7%)
In the maintenance study, adverse event rates were comparable across all groups, with the most commonly reported events being ulcerative colitis, COVID-19, and arthralgia. Notably, there were no reports of active tuberculosis, anaphylaxis, serum sickness, or clinically significant hepatic disorders in either study.
Discussion
Ulcerative colitis (UC) is a disabling disease with long-term consequences for its sufferers. Due to its chronic and progressive nature, UC often leads to disability and is frequently misdiagnosed or difficult to manage effectively. While various treatments exist, biologics have emerged as the key to long-term success in managing the disease.
Doctors, funders, or patients have not universally accepted the advent of powerful disease-modifying agents that can induce full remission. The continued reliance on older, ineffective, and sometimes toxic treatments needs to be re-evaluated. The medications available over the past 26 years should be recognised as the standard of care for UC patients.4
Biologics, which target the different pathways in the immune cascade, including newer agents like guselkumab, have shown comparable effectiveness. They are effective and well-tolerated therapy for moderately to severely active UC.
As shown in this study, guselkumab can induce significant clinical remission in both induction and maintenance phases underscores its potential as a treatment option.
Furthermore, the safety profile illustrated by this study, with no reports of serious complications such as tuberculosis or hepatic disorders, further supports its use in the management of UC.
Conclusion
The researchers conclude that their findings demonstrate that gesumkalab is a safe and effective therapy for patients inadequately managed with conventional or advanced treatments.
Importance of this study for South Africa
Ulcerative colitis (UC) is an emerging global health issue, yet its incidence in South and sub-Saharan Africa remains largely unreported.3
Limited data exists on its prevalence outside South Africa, and disparities in healthcare access across the region further complicate the available information. Early studies from the 1980s suggested that UC was relatively rare among the Black population in South Africa. However, recent evidence indicates a shift, with cases of UC increasing in both South Africa and other parts of Africa, in line with trends observed in regions like Asia. This rise highlights the urgent need for further research to establish the prevalence of UC across the continent accurately.3
In South Africa, biologics have become a critical tool in managing UC, but their use comes with challenges. The high cost of biologic therapies remains the primary concern, along with the increased susceptibility to tuberculosis (TB), delays in initiating treatment, and long-term risks such as colon cancer. 2,4
Despite these concerns, biologics and other disease-modifying treatments are lifelines for UC patients, offering the potential for long-term remission and improved quality of life. There is a pressing need to revisit the treatment timelines and healthcare strategies to ensure more timely access to these critical therapies, ultimately improving patient outcomes and reducing the long-term burden of the disease.
Additional References
1. Allocca, M., Furfaro, F., Fiorino, G., Gilardi, D., D'Alessio, S., & Danese, S. (2018). Can IL-23 be a good target for ulcerative colitis?. Best practice & research. Clinical gastroenterology, 32-33, 95–102. https://doi.org/10.1016/j.bpg.2018.05.016
2. D'Amico, F., Parigi, T. L., Bonovas, S., Peyrin-Biroulet, L., & Danese, S. (2020). Long-term safety of approved biologics for ulcerative colitis. Expert opinion on drug safety, 19(7), 807–816. https://doi.org/10.1080/14740338.2020.1773430
3. Hodges, P., & Kelly, P. (2020). Inflammatory bowel disease in Africa: what is the current state of knowledge?. International health, 12(3), 222–230. https://doi.org/10.1093/inthealth/ihaa005
4 Wright J. (2024). The current standard of care of inflammatory bowel disease. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 114(3), e1792. https://doi.org/10.7196/SAMJ.2024.v114i3.1792
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