Latest data for subcutaneous guselkumab in CD and UC

Treatment with subcutaneously administered guselkumab was superior to placebo in inducing and maintaining clinical and endoscopic endpoints in patients with moderately to severely active Crohn’s disease (CD). Week 12 results of the phase 3 ASTRO trial also showed that subcutaneous guselkumab was efficacious and safe in patients with ulcerative colitis (UC).

GRAVITI

In the phase 3 GRAVITI study (NCT05197049), 347 participants with CD and an inadequate response to oral corticosteroids, biologic therapies, methotrexate, azathioprine, or mercaptopurine were randomised 1:1:1 to:

• subcutaneous guselkumab 400 mg every 4 weeks up to week 12, followed by guselkumab 200 mg every 4 weeks up to week 96;
• subcutaneous guselkumab 400 mg every 4 weeks up to week 12, followed by guselkumab 100 mg every 8 weeks up to week 96; or
• placebo; guselkumab rescue therapy was allowed from week 16.

The co-primary endpoints were clinical remission at week 12 and endoscopic response at week 12. Prof. Ailsa Hart (London North-West University, UK) presented the key findings of the trial [1].

At week 12, the clinical remission rate was 56.1% in the guselkumab arms and 21.4% in the placebo arm (Δ34.9; 95% CI 25.1–44.6; P<0.001). Moving to endoscopic response at week 12, the authors reported rates of 41.3% for participants treated with guselkumab and 21.4% for those on placebo (Δ19.9; 95% CI 10.2–29.6; P<0.001). “These findings were consistent across biologic-naïve and biologic-experienced patient groups,” added Prof. Hart. At week 48, clinical remission rates were 60.0% for participants in the 100 mg arm, 66.1% for participants in the 200 mg arm, and 17.1% for participants on placebo.

“After 4 weeks, there was already a clear difference between guselkumab and placebo in terms of clinical remission rates,” said Prof. Hart. “The results we observed at week 12 were maintained up to week 48 with maintenance therapy.” Deep remission was observed for 26.1%, 33.9%, and 4.3% of the participants in the 100 mg, 200 mg, and placebo arms, respectively.

The serious adverse event (AE) rate was higher in the placebo arm (37.1 events per 100 patient-years) than in the guselkumab arms (13.2–15.5 events per 100 patient-years). The most frequently reported AEs in participants on guselkumab were upper respiratory tract infections (14%), abdominal pain (10%), COVID-19 (8%), CD (6%), and headache (6%).

ASTRO

In the phase 3 ASTRO study (NCT05528510), subcutaneous guselkumab was tested in participants with moderately to severely active UC. In the 12-week induction phase, participants were randomised to subcutaneously administered guselkumab 400 mg every 4 weeks (n=279) or to placebo (n=139). Prof. Laurent Peyrin-Biroulet (University of Lorraine, France) shared the findings [2].

At week 12, the primary endpoint of clinical remission was reached by 27.6% of the participants in the guselkumab arm and by 6.5% of the participants in the placebo arm (Δ21.1%; 95% CI 14.5–27.6; P<0.001). The corresponding rates in bio-naïve participants (36.0% vs 8.0%; nominal P<0.001) and bio-experienced participants (16.1% vs 3.6; nominal P=0.005) demonstrated that guselkumab was efficacious, irrespective of biologic therapy status. Endoscopic improvement was observed in 37.3% and 12.9% of the participants on guselkumab and placebo, respectively. The stringent endpoint of histo-endoscopic mucosal improvement was achieved by 30.5% of the participants in the guselkumab group and by 10.8% of those in the placebo group.

According to Prof. Peyrin-Biroulet, the safety profile of subcutaneous guselkumab was consistent with the well-characterised and favourable safety profile of guselkumab in approved indications. “We saw 2 serious infections in the guselkumab arm; 1 case of pilonidal disease, and 1 case of gastroenteritis, both resolving without drug interruptions.”

In conclusion, GRAVITI showed that subcutaneously administered guselkumab induction and maintenance therapy was efficacious and safe in patients with moderately to severely active CD, and ASTRO demonstrated that subcutaneously administered guselkumab was a safe and efficacious induction therapy in UC. “The results of the GRAVITI study are similar to those of GALAXI, in which guselkumab was administered intravenously to patients with CD, providing physicians the flexibility to choose how they would like to treat their patients,” concluded Prof. Hart. Similarly, although no direct comparison was performed, the results of subcutaneously administered guselkumab induction appeared to be comparable with those of intravenously administered guselkumab induction therapy in UC, findings of the phase 3 QUASAR study indicated [3].

1. Hart A, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in patients with moderately to severely active Crohn’s disease: results through week 48 from the phase 3 GRAVITI study. OP33, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.
2. Peyrin-Biroulet L, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in patients with ulcerative colitis: results through week 12 from the phase 3 ASTRO study. OP10, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.
3. Rubin DT, et al. Lancet. 2025;405(10472):33-49.

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Posted on 8 April 202514 April 2025