Guselkumab provides benefits in UC regardless of advanced therapy history

Induction therapy with guselkumab was efficacious in participants with moderately to severely active ulcerative colitis (UC), irrespective of treatment history with advanced therapies. The phase 3 QUASAR trial results demonstrated the benefits of guselkumab over placebo across clinical, symptomatic, and endoscopic endpoints.

“The IL-23 inhibitor guselkumab has been approved for the treatment of plaque psoriasis and psoriatic arthritis,” said Prof. Axel Dignass (Goethe University, Germany) at the start of his presentation [1]. To further assess the potential of this agent, the phase 3 QUASAR induction study (NCT04033445) compared the efficacy of guselkumab and placebo in participants with moderately to severely active UC who had an inadequate response or intolerance to corticosteroids, immunosuppressants, and/or advanced therapies (ADT) such as TNF inhibitors, integrin receptor antagonists, or JAK inhibitors. The participants (n=701) were randomised 3:2 to guselkumab 200 mg, intravenously administered every 4 weeks, or placebo. Prof. Dignass presented the efficacy results at week 12, stratified by the history of inadequate response or intolerance to ADT.

In total, 49% (n=344) of the participants had an inadequate response or intolerance to ADT. Among them, approximately 88%, 54%, and 18% of the participants were non-responsive or intolerant to TNF inhibitors, integrin receptor antagonists, and/or JAK inhibitors, respectively. In the population with no history of inadequate response or intolerance to ADT (n=357), 32.4% of the participants on guselkumab achieved clinical remission compared with 11.8% of those on placebo (P<0.001). For symptomatic remission, the corresponding rates were 61% and 27.1% (P<0.001).

In the population with inadequate response or intolerance to ADT, clinical remission was reached by 12.5% of the participants on guselkumab and by 3.7% of those on placebo (P=0.005). For symptomatic remission, the rates were 38.5% and 14% for the guselkumab arm and placebo arm, respectively (P<0.001; see Figure). “Looking at additional endpoints, among the population without inadequate response or intolerance to ADT, endoscopic improvement was observed in 38.5% and 16.7% of the participantson guselkumab or placebo, respectively (P<0.001), and endoscopic normalisation was seen in 21.1% and 7.6% of cases, favouring the guselkumab arm over the placebo arm (P<0.001),” added Prof. Dignass. In the population with inadequate response or intolerance to ADT, the rates of endoscopic improvement were 14.9% and 5.1% (P=0.005), and the rates of endoscopic normalisation were 8.7% and 2.2% (P=0.015).

Figure: Clinical endpoints at week 12 by advanced therapy history [1]



ADT-IR, inadequate response or intolerance to advanced therapy; GUS, guselkumab; IV, intravenous; PBO, placebo.

To sum up, guselkumab induction therapy outperformed placebo across various efficacy endpoints in participants with UC, regardless of their advanced therapy treatment history.

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   1. Bressler B, et al. The efficacy of induction treatment with guselkumab in patients with moderately to severely active ulcerative colitis: phase 3 QUASAR induction study results at week 12 by prior advanced therapy history. OP019, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December, 20238 April, 2024