Guselkumab shows encouraging safety and efficacy in ulcerative colitis

Guselkumab induction therapy was superior to placebo across key endpoints in patients with moderately to severely active ulcerative colitis (UC) in the phase 2b QUASAR trial. Moreover, the results showed a favourable safety profile of guselkumab in the study population.

Guselkumab is an IL-23 inhibitor, approved for the treatment of psoriatic arthritis and psoriasis, and currently under investigation as a therapy for patients with inflammatory bowel disease (IBD), explained Prof. Axel Dignass (Agaplesion Markus Hospital, Germany) [1]. The double-blind, placebo-controlled, phase 2b QUASAR Induction Study 1 (NCT04033445) randomised 313 patients with moderately to severely active UC, who failed on conventional or advanced therapies, 1:1:1 to intravenous 400 mg guselkumab, 200 mg guselkumab, or placebo every 4 weeks. The primary endpoints were clinical response^a and clinical remission^b at week 12.

The proportion of patients achieving clinical response at week 12 were significantly higher in the guselkumab 400 mg arm (60.7%) and the guselkumab 200 mg arm (61.4%) as compared with placebo (27.6%; P<0.001). The proportion of patients in clinical remission at week 12 confirmed the superiority of guselkumab (400 mg 25.2%; 200 mg 25.7%) over placebo (9.5%; P<0.05) in this study population. Furthermore, secondary endpoints at week 12 demonstrated efficacy benefits of guselkumab (combined arms) over placebo, including symptomatic remission^c (49.0% vs 20.0%; P<0.001), endoscopic improvement^d (30.8% vs 12.4%; P<0.001), histo-endoscopic mucosal improvement^e (23.6% vs 8.6%; P<0.001), and endoscopic normalisation^f (15.9% vs 6.7%, P<0.05).

Guselkumab was well tolerated in this patient population and no notable differences in key safety events were reported between the low-dose and high-dose guselkumab arms. No significant difference was detected in the occurrence of adverse events (AEs) between participants who received placebo (55.2%) and participants who received guselkumab (46.2%). Serious AE proportion was higher in the placebo arm (5.7%) than in the combined guselkumab arms (1.0%). Importantly, the proportion of infections were comparable across groups (placebo 11.4% vs guselkumab 10.6%).

Prof. Dignass added that no dose response was observed for guselkumab. He mentioned that it could be that the lower dose of guselkumab (200 mg) is already the optimal dose for these patients, but further analyses need to be performed to clarify this point.

a. Clinical response is defined as decrease from induction baseline in de modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore of 0 or 1.

b. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.

c. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.

d. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

e. Histo-endoscopic mucosal improvement is defined as achieving a combination of histologic improvement (neutrophil infiltration in <5 percent of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement.

f. Endoscopic normalisation is defined as an endoscopy subscore of 0.

1. Dignass A, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active Ulcerative Colitis: Phase 2b QUASAR Study results through week 12. OP23, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024