P954 Cumulative response to guselkumab through week 24 of induction in patients with moderately to severely active ulcerative colitis: Results from the phase 3 QUASAR induction study
Authors: Rubin D , Sands B , Lichtenstein G , Baker T , Huang K H , Germinaro M , Miao Y , Zhang H , Nancey S , Allegretti J , Feagan B , Hisamatsu T , Panés J , Dignass A , Bressler B , Peyrin-Biroulet L 
Published: January 2024

Background

The Phase 3 QUASAR induction study evaluated efficacy and safety of guselkumab (GUS), an IL-23p19 subunit antagonist, in pts with moderately to severely active UC. At Week (Wk) 12, GUS 200mg IV was more effective than placebo (PBO) in inducing clinical remission and clinical response.1 Pts not in clinical response at Wk 12 received GUS through Wk 24. Here, we report GUS cumulative efficacy and safety.

Methods

Pts with a modified Mayo score of 5-9 and a centrally reviewed Mayo endoscopy subscore ≥2 at baseline (BL) were randomized 3:2 to receive GUS 200mg IV or PBO at Wks 0, 4, and 8. Pts not in clinical response at Wk 12 received GUS at Wks 12, 16, and 20 (GUS 200mg IV→GUS 200mg SC; PBO→GUS 200mg IV) and were evaluated at Wk 24. Matching IV or SC PBO were used to maintain study blinding. Final safety assessments were conducted through Wk 32 (ie, 12 wks after last dose of GUS).

Results

The primary analysis population consisted of 701 pts. BL demographics were similar among treatment groups, and approximately 50% had a history of inadequate response/intolerance to advanced therapy (ADT-IR).

At Wk 12, clinical response was achieved by a higher percentage of GUS- vs PBO-treated pts (61.5% vs 27.9%, respectively; adjusted Δ [95% CI]: 33.8% [26.9%, 40.7%]; p&lt;0.001; Figure). Of GUS-treated pts who were not in clinical response at Wk 12 and received additional GUS treatment (GUS IV→GUS SC), 55% (66/120) achieved clinical response at Wk 24. Cumulative clinical response at Wk 12 or 24 was achieved by 77.2% of pts randomized to GUS at BL. Pts with and without history of ADT-IR benefitted from continued treatment with GUS SC through Wk 24 (51.4% and 60.9% achieved clinical response at Wk 24, respectively). Of PBO-treated pts who were not in clinical response at Wk 12 and received GUS treatment (PBO IV→GUS IV), clinical response rate at Wk 24 (69.7%) was similar to that at Wk 12 for pts randomized to GUS at BL (61.5%). Safety findings through the final safety visit were consistent with Wk 12 results;1 no new safety signals were identified (Table). The most frequent adverse events among GUS-treated pts (n=586) were COVID-19 (7.2%), anemia (5.1%), and worsening UC (4.6%).

Conclusion

Among pts randomized to GUS IV who did not achieve clinical response at Wk 12, continued treatment with GUS SC allowed 55% to achieve clinical response at Wk 24. Overall, more than three-quarters of pts randomized to GUS IV achieved clinical response at Wk 12 or 24. No new safety signals for GUS were identified.

1) Allegretti JR, Peyrin-Biroulet L, Feagan BG, et al. The efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 QUASAR induction study. UEG Journal. 2023;11(58):45-6.