Phase 3 FUZION Data Support Guselkumab in Perianal Fistulizing Crohn’s Disease

Perianal manifestations of Crohn's disease remain among the most difficult complications to manage, even in an era defined by expanding biologic options. Despite decades of therapeutic progress, durable fistula healing continues to be elusive for many patients, leaving a substantial unmet need for effective, evidence-based treatments.

Guselkumab Shows Efficacy in Perianal Fistulizing Crohn’s Disease

New findings from the phase 3 FUZION study presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, offer encouraging data for guselkumab in patients with active perianal fistulizing disease. In an interview with HCPLive, Laurent Peyrin-Biroulet, MD, PhD, highlighted both the clinical significance of the results and their potential to reshape treatment strategies in this historically challenging population.

As Peyrin-Biroulet emphasized, perianal Crohn’s disease is not only common, but also associated with significant morbidity, including abscess formation, repeated surgeries, and long-term bowel damage. While infliximab transformed management decades ago, limitations in efficacy and safety have underscored the need for additional options supported by robust randomized data.

Clinically Meaningful Fistula Remission at Week 24

The FUZION trial evaluated guselkumab in adults with ≥1 active draining perianal fistula and prior inadequate response to conventional or advanced therapies. Patients were randomly assigned to 2 dosing regimens of guselkumab or placebo, with the primary endpoint defined as combined fistula remission at week 24, a stringent measure requiring both clinical closure and radiographic resolution on MRI.

Results showed that guselkumab significantly outperformed placebo. Approximately 28% of patients receiving guselkumab achieved combined fistula remission at week 24, compared with just over 10% in the placebo group, representing a treatment difference of more than 15%. Clinical fistula response rates were even higher, with roughly one-third of patients achieving meaningful improvement.

“I think that this is something that we are very interested as clinicians, is that when you are looking there is already a statistical difference at week 12, after only 3 months of treatment,” Peyrin-Biroulet noted, pointing to the potential for relatively rapid clinical benefit in a population where treatment responses are often slow and incomplete.

Safety Profile and Dosing Considerations

Safety findings were consistent with the known profile of guselkumab, with no new signals identified. For clinicians, this contributes to what Peyrin-Biroulet described as a favorable risk-benefit balance, particularly when compared with older therapies associated with higher risks of infection.

The study also evaluated 2 dosing strategies, which showed similar efficacy at the population level. However, Peyrin-Biroulet noted that higher dosing may still play a role in specific subgroups, such as patients with more severe or refractory disease, where greater drug exposure may be required to achieve optimal outcomes.

Implications for First-Line Advanced Therapy

Beyond efficacy, the importance of FUZION is its contribution to a limited evidence base. Few randomized controlled trials have specifically targeted perianal fistulizing Crohn’s disease, making these findings particularly impactful.

According to Peyrin-Biroulet, the strength of the data positions guselkumab as a potential first-line advanced therapy option for patients with this phenotype, pending regulatory and access considerations.

“When you are looking at this data, clearly, there is a very good risk benefit profile, very good efficacy data, so it should be positioned as a first line treatment in case of a patient needing an advanced therapy,” he said.

As the treatment landscape continues to evolve, these results represent an important step toward improving outcomes in a patient population that has long been underserved by clinical research and therapeutic innovation.

Editors’ note: Peyrin-Biroulet reports relevant disclosures with Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Novartis, and others.

References

1. Peyrin-Biroulet L, Jairath V, Hart A, et al. GUSELKUMAB FOR PERIANAL FISTULIZING CROHN’S DISEASE: WEEK 24 RESULTS FROM THE PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER FUZION STUDY. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

2. Johnson & Johnson. Johnson & Johnson study shows TREMFYA® (guselkumab) is the first and only IL-23 inhibitor to demonstrate efficacy in perianal fistulizing Crohn’s disease. May 5, 2026. Accessed May 6, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-study-shows-tremfya-guselkumab-is-the-first-and-only-il-23-inhibitor-to-demonstrate-efficacy-in-perianal-fistulizing-crohns-disease