Guselkumab demonstrates superior efficacy in landmark clinical trials and offers new hope to Crohn’s disease patients

Guselkumab is the first biologic shown in identically designed, 48-week, double-blind trials to outperform another leading biologic—ustekinumab, a monoclonal antibody that blocks both IL-12 and IL-23—for key markers of disease remission and gut healing in Crohn’s disease. The design allowed for head-to-head comparisons to both placebo and ustekinumab. The studies enrolled 1,048 patients worldwide and randomly assigned participants to one of four groups:

• guselkumab 200 mg intravenously (IV) at weeks 0/4/8, then guselkumab 100 mg subcutaneously (SC) every eight weeks beginning at week 16

• guselkumab IV at weeks 0/4/8, then guselkumab 200 mg every four weeks beginning at week 12

• ustekinumab ~6 mg/kg IV at week 0, then ustekinumab 90 mg SC every eight weeks beginning at week 8

• placebo

Guselkumab demonstrated statistically significant improvements across multiple endpoints, including endoscopic response and deep remission. Safety outcomes, based on adverse events and laboratory findings, were favorable and consistent with the known profile of guselkumab in approved indications.

Beyond symptom control, the therapy’s corticosteroid-sparing effect further underscores its clinical value, especially for patients seeking alternatives to long-term steroid use.

The GALAXI 2 and 3 trials were sponsored by Johnson & Johnson and enrolled patients with prior biologic treatment failures.

Dr. Sands, the Chief of Mount Sinai’s Dr. Henry D. Janowitz Division of Gastroenterology, is a renowned expert in inflammatory bowel disease. He previously co-authored the pivotal UNITI trial, and was both the lead author and corresponding author on the UNIFI trials. Both of these trials helped establish ustekinumab’s place in IBD care. His latest work builds on that legacy, demonstrating not only the effectiveness of IL-23 inhibition but its potential to redefine front-line treatment.