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New QUASAR analysis shows patients with intolerance or failed response to advanced therapies nonetheless achieved benefit with guselkumab.
Induction of intravenous (IV) guselkumab 200 mg for the treatment of moderately to severely active ulcerative colitis (UC) was associated with greater improvement to clinical, symptomatic and endoscopic outcomes versus placebo, regardless of patient history of advanced therapy intolerance.
Though the new data from the phase 3 QUASAR induction study did show most significantly greater benefit of treatment in patients without an intolerance to advanced therapy options, the findings provide confidence that a prior intolerance to agents like tumor necrosis factor (TNF) antagonists or Janus kinase (JAK) inhibitors should not deter use of guselkumab for patients with UC.
The findings from the QUASAR study were reported in a poster presentation at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, BC this week.
Led by Brian Bressler, MD, MS, of St. Paul’s Hospital in Vancouver, the international team of investigators sought to analyze induction efficacy results for guselkumab versus placebo in QUASAR trial participants based on individual history of inadequate response, loss of response, or intolerance to advanced therapy. The phase 3 pivotal QUASAR study was a randomized, double-blind, placebo-controlled trial evaluating the interleukin 23 (IL-23) antagonist in patients with moderately to severely active UC and a history of difficulty in care with drug classes including corticosteroids; immunosuppressants; TNF antagonists; JAK inhibitors like tofacitinib; or integrin receptor antagonists like vedolizumab.
In QUASAR, patients were randomized 3:2 to either IV guselkumab 200 mg or placebo at every 4 weeks through week 8. Eligible patients for the primary analysis had a modified Mayo score of 5 – 9, as well as a centrally reviewed endoscopy subscore of ≥2, at baseline. Bressler and colleagues sought a primary endpoint of UC clinical remission at week 12. The team additionally assessed for symptomatic remission; clinical response; endoscopic improvement; histo-endoscopic mucosal improvement (HEMI); and endoscopic normalization at week 12.
The final primary analysis included 701 patients. Approximately half (n = 357 [50.9%]) had no history of intolerance to advanced therapy; of that subgroup, 95.0% were naïve to advanced therapy. The remaining 344 (49.1%) patients had a history of advanced therapy intolerance.
Patients with a history of failed treatment with advanced therapies for their UC had longer disease duration at baseline (mean, 8.9 years) versus patients without such a history (mean, 6.2 years). They additionally reported greater rates of severe endoscopic disease per subscores of ≤3 (78.5% vs 57.7%), higher median CRP (5.3 mg/L vs 3.4 mg/L) and greater median fecal calprotectin (1647 mg/kg vs 1589 mg/kg) at baseline than patients without a history of advanced therapy failure.
Respective rates of inadequate response, loss of response, or intolerance to certain advanced therapies were as follows among the 344 patients:
Bressler and colleagues observed that treatment differences among the guselkumab and placebo arms were generally greater among the subgroup of patients without a history of advanced therapy intolerance compared to those with such prior issues. However, overall, a greater proportion of patients receiving the IL-23 treatment achieved the primary and key secondary endpoints in both subgroups versus the placebo subgroups at week 12.
“Induction treatment with guselkumab 200 mg IV versus placebo resulted in greater improvements across key clinical, symptomatic, and endoscopic/histologic outcomes at week 12 among moderately to severely active UC patients with and without a history of advanced therapy intolerance,” investigators concluded.
Bressler B, Peyrin-Biroulet L, Allegretti JR, Huang KHG, et al. 34 - Early Symptomatic Improvement With Guselkumab Induction Treatment in Moderately to Severely Active Ulcerative Colitis: Results from the Phase 3 QUASAR Induction Study. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.