Guselkumab Shows Improved Outcomes in Crohn’s Disease: Insights From GALAXI, With Anita Afzali, MD

Recent findings from 2 post hoc subgroup analyses of GALAXI phase 2b and 3 trial highlight guselkumab’s improved clinical and endoscopic outcomes in treating patients with moderately to severely active Crohn’s disease (CD).

The data was presented in dual abstracts at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting by Anita Afzali, MD, MPH, Professor of Clinical Executive Vice Chair, Internal Medicine at the University of Cincinnati, who offered insights into the evolving landscape of inflammatory bowel disease and its effective treatments. The promising clinical effects of guselkumab, a dual-acting IL-23 antagonist and P19 inhibitor, have been proven in patients with moderately to severely active CD, defined as Crohn’s Disease Activity Index (CDAI) 220-450 and a mean daily stool frequency (SF) score >3 or AP score >1.1,2

In September 2025, the US Food and Drug Administration (FDA) approved subcutaneous induction of guselkumab, making it the first IL-23 inhibitor with a dual subcutaneous and intravenous induction option for the treatment of ulcerative colitis and CD. The randomized double-blind, placebo-controlled, parallel-group, multicenter, treat-through phase 3 study, ASTRO, showed early symptomatic response improvements in guselkumab-treated patients as early as 2 weeks into the trial and sustained through week 24.

Further analysis of GALAXI 2 & 3 phase 3 treat-through studies strived to determine whether increased maintenance doses would improve results in patients with greater inflammatory burden and disease severity at baseline. The clinical outcomes of clinical remission, a CDAI < 150, and endoscopic response, ≥50% improvement in simple endoscopic score (SES-CD) or SES-CD≤2, were compared in a randomly-assigned dosing of subcutaneous 100mg q84 versus 200mg q4w. Those with high disease activity at baseline, defined as CDAI >300 or SES-CD >12, greater inflammatory burden after induction, or who had not achieved an endoscopic response after induction, saw a greater clinical and endoscopic outcome when introduced to the higher dose of 200 mg q4w.1

“If there was a higher burden of inflammation, a higher baseline CDAI score, a higher SCS CD score, or the patient did not have an endoscopic response or a CRP response after induction doses, patients were more likely to achieve better outcomes if they were on the higher maintenance dose,” Afzali said in an interview with HCPLive. “This was a great post hoc to help us determine what we do when it comes to maintenance dosing. And I think for my actual clinical practice, I'm going to go straight to that 200 milligrams every 4 weeks because we have patients who have a high level of inflammatory burden, and these are the patients we want to get it right.”

Additional data from the phase 2b and 3 studies showed clinical improvement in 80 patients who were non-responsive to treatment by ustekinumab 90mg SC q8w when switched to 200 mg guselkumab q4w without IV induction. Investigators collected patient data 16 weeks after treatment, showing that more than 50% had achieved clinical remission. In a year, follow-up, 96 weeks after the treatment switch, 50% of patients achieved an endoscopic response.2

“So among these patients, without an induction, they were able to have efficacy, and we did not see any other safety concerns either. I think this really helps us when we talk about not just positioning, but also sequencing of therapies,” concluded Afzali. “A very common question I'm asked is, ‘Well, if my patient was previously on ustekinumab, may I or should I or could I still consider guselkumab?’ And this subgroup analysis offers a ‘yes’ to us for the right patient to determine that maybe this is an option for that right individual.”2

Editor's note: Afzali reports relevant disclosures with AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Johnson & Johnson, Takeda, and others.

References

1. Afzali A, Wolf D, Leong R, Van Rampelbergh R. Efficacy and Safety of Subcutaneous Guselkumab Rescue ... : Official journal of the American College of Gastroenterology | ACG. LWW. Published online October 2025. https://doi.org/10.14309/01.ajg.0001133276.53761.51

2. Alzali A, Hisamatsu T, Rubin D. S1452 Guselkumab Maintenance Dose Regimens in Patients With ... : Official journal of the American College of Gastroenterology | ACG. LWW. Published online October 2025. https://doi.org/10.14309/01.ajg.0001133268.32992.d0