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Induction treatment with guselkumab resulted in a rapid onset of efficacy, beginning at week 1 and increasing over time to week 12, for patients with refractory moderately to severely active ulcerative colitis.
Induction treatment with the interleukin-23 p19 subunit antagonist guselkumab (Tremfya) resulted in symptomatic improvements within 1 week for patients with moderately to severely active ulcerative colitis (UC), according to findings from the phase 3 QUASAR Induction Study presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, Canada.
In the study, symptomatic response was seen between the guselkumab group and the placebo arm as early as week 1, with a difference of 9.5 percentage points (P <.01).By week 12, the difference between groups was 37.0 percentage points (P <.001). A statistically significant difference between groups in symptomatic remission was seen at week 4, with a difference between groups of 9.9 percentage points (P <.001). By week 12, the difference in symptomatic remission rates was 29.4 percentage points (P <.001).
"We see a rapid onset of efficacy, beginning at week 1 and increasing over time to week 12, there was symptomatic response that was better than the placebo group. In a similar vein, starting at week 4, this achieved significance for symptomatic remission and continued to differentiate until week 12," lead investigator Gary Lichtenstein, MD, from the University of Pennsylvania, said during a presentation of the results. "This was a relatively refractory population, so this may not represent a population one sees. Others may perhaps do much better."
In the QUASAR induction trial, patients were randomized 3:2 to receive guselkumab at 200 mg intravenously (n = 421) or matched placebo (n = 280) at baseline and weeks 4 and 8. The mean age of patients was 40.5 years and patients had a mean duration of UC disease duration of 7.52 years. Nearly two-thirds of patients (64.5%) had severe UC, as indicated by a Modified Mayo score of 7 to 9. The mean modified Mayo score was 6.9. "This is a refractory population that is being evaluated," Lichtenstein noted.
Across all patients, approximately half (49.1%) had a history of inadequate response, loss of response, or intolerance to conventional therapies and/or advanced therapies. Of these patients (n = 344), the most common treatment received were tumor necrosis factor alpha antagonists (87.5%), vedolizumab (54.1%), and/or tofacitinib (18.0%). Nearly half had received 2 or more advanced therapy classes (47.4%) and 12.2% had received 3 advanced therapy classes.
A significant difference in stool frequency (SF) subscore of 0 or 1 was seen at week 1 between groups. At this point, there was a 6.9 percentage point difference between guselkumab and placebo (P <.05). By week 12, 60.1% of patients had an SF of 0 or 1 compared with 31.8% in the placebo group (P <.001), a difference of 28.5 percentage points. Rectal bleeding subscore of 0 reached a statistically significant difference between groups at 4 weeks, with a 14.1 percentage point difference (P <.001). By week 12, 64.6% had a rectal bleeding sub score of 0 in the guselkumab arm vs 28.6% in the placebo group, for a 36.2 percentage point difference (P <.001).
"Beginning as early as week 1 and increasing over time until week 12 there was difference between active therapy vs placebo in achieving a stool frequency subscore of 0 or 1," said Lichtenstein. "In a similar vein, rectal bleeding subscore had a similar pattern over placebo, achieving a rectal bleeding score of 0 over time."
The change in absolute stool number from baseline was statistically different at week 1 between arms. In the guselkumab arm, there was a -0.77 change vs a -0.37 change for placebo (P <.05). By week 12, there was a mean difference of 1.79 between arms, with a -3.15 change in absolute stool number in the guselkumab arm vs a -1.36 change in the placebo group. A -0.1 difference in rectal bleeding was seen at week 1 (P <.05) and by 12 weeks the difference was -0.7 (P <.001).
"The absolute numbers are perhaps more clinically relevant, and this was a continuous variable assessed during the study. You can see early differentiation and increase over time of the absolute stool number as well as the rectal bleeding subscore," said Lichtenstein. "This is a relatively rapid onset of benefit."
At this point, guselkumab has not yet been approved for ulcerative colitis. It is approved for patients with moderate to severe plaque psoriasis and active psoriatic arthritis.
Lichtenstein GR, Dignass A, Rubin DT, et al. Early Symptomatic Improvement With Guselkumab Induction Treatment in Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3 QUASAR Induction Study. Presented at: ACG 2023 Annual Meeting; October 20-25, 2023. Abstract 34.