Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).

“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.

The researchers also divided the results by prespecified subgroups based on previous treatments.

Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).

“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.

Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% and ≥ 2 points, with either a ≥ 1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).

Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group compared with 25.0% in the placebo group (P < .001).

Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall compared with 12.9% of those in the placebo group achieved this endpoint (P < .001).

“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”

In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.

The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.

The GRAVITI Study

In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.

The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.

In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.

The co-primary endpoints were clinical remission and endoscopic response at week 12.

Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, England, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting last October.

At week 12, 56.1% of patients who received guselkumab achieved clinical remission compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumabcompared with 21.4% in the placebo group.

Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.

Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose compared with 6.8% of patients on placebo.

In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group compared with 6.0% in the placebo group.

Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.

“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said.

Furthermore, data from the ASTRO study demonstrated similar data in the UC population, she added.

As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.

Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” co-moderator, Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, told Medscape Medical News.

It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”

Source

Subcutaneous Guselkumab Proves Efficacious for IBD