A recent phase 3 study has demonstrated that subcutaneous guselkumab induction therapy is effective in treating patients with moderately to severely active ulcerative colitis (UC). Conducted as a randomized, double-blind, placebo-controlled trial known as the ASTRO study, the research aimed to evaluate the therapy's efficacy and safety.
The study's co-primary endpoints focused on clinical remission and endoscopic response at week 12. Results indicated that 36% of patients naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate (S1P) modulators achieved clinical remission after receiving guselkumab, compared to just 8.9% in the placebo group (P < 0.001). Among patients who previously received these treatments, 16.1% in the guselkumab group achieved clinical remission versus 3.6% in the placebo group (P = 0.005).
Endoscopic remission was also notable, with 38.3% of patients in the 200-mg guselkumab group and 30.4% in the 100-mg group achieving this outcome, compared to only 6.0% in the placebo group. Furthermore, clinical response—defined as a decrease in the modified Mayo score by at least 30% and a reduction in rectal bleeding—was observed in 65.6% of the guselkumab group, while only 34.5% of the placebo group experienced similar improvements (P < 0.001).
The findings from the ASTRO study suggested that subcutaneous induction therapy aligns with the previously established efficacy of intravenous (IV) guselkumab for UC. Notably, the rate of clinical remission increased to over three times higher at 48 weeks with both maintenance doses of guselkumab, achieving rates of 66.1% and 60.0%, compared to only 17.1% in the placebo group.
Endoscopic response rates were similarly promising, with 41.3% of patients treated with guselkumab compared to 21.4% in the placebo cohort. This efficacy was further supported by data from the GRAVITI study, which followed similar induction and maintenance dosages and treatment intervals as the ASTRO study.
Guselkumab functions as a selective dual-acting interleukin (IL)-23p19 subunit inhibitor, effectively blocking IL-23 while binding to CD64, a receptor associated with IL-23 production. The results of this study were presented at the European Crohn’s and Colitis Organisation (ECCO) Congress in 2025 and align with findings from the QUASAR study, which reported clinical remission rates of 22.6% with IV guselkumab at week 12.
The safety profile observed in this trial was consistent with existing knowledge regarding guselkumab’s safety in approved indications and other studies related to inflammatory bowel disease (IBD).
Peyrin-Biroulet, a prominent researcher involved in the study, remarked on its implications, stating, “These results are in line with the QUASAR data.” He emphasized that achieving clinical remission rates over 20% is considered a significant milestone: “We know that when it is over 20%, it is considered game changer.” He further added, “This is a treatment effect of over 20%,” highlighting the substantial impact of guselkumab therapy on patient outcomes.
In discussing the symptomatic remission observed at week 12, Peyrin-Biroulet noted that “the difference between the overall guselkumab result and placebo was 30%.” This statistic underscores the potential efficacy of guselkumab in altering disease progression.
Hart, another researcher associated with the study, affirmed its significance: “These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease.” The findings imply broad therapeutic options for patients suffering from IBD.
Bamias added an interesting perspective on treatment choices: “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.” This statement reflects a growing body of evidence supporting various treatment modalities for UC.
Although clinicians may choose between subcutaneous and IV administration pragmatically, Hart emphasized that both methods exhibit efficacy. He stated that “the rationale for choosing subcutaneous or IV is likely to be pragmatic.”
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