Treatment with guselkumab results in significantly higher rates of combined fistula remission at week 24 in adults with active perianal fistulizing Crohn’s disease (PFCD) compared with placebo, according to the FUZION trial presented at DDW 2026.
PFCD affects approximately one-fourth of patients, often leading to perianal abscesses, pain and persistent drainage/discharge, and faecal incontinence, as well as impaired quality of life. Despite combined medical and surgical interventions, achieving durable fistula healing remains a major unmet need.
“FUZION is the first successful international phase III trial assessing the combined clinical and MRI primary endpoint, and the first in more than two decades showing the efficacy of an advanced therapy in PFCD,” said study author Prof Laurent Peyrin-Biroulet from Nancy University Hospital in France.
This phase III, double-blind, treat-through study included 286 patients (mean age 36.5 years, 71.7 percent male) with ≥1 active draining perianal fistula confirmed by blinded central MRI review and a Crohn’s Disease Activity Index of <350 who had an inadequate response to conventional or advanced therapy. Participants were randomized 2:2:1 to receive intravenous guselkumab 200 mg Q4W during the induction period, followed by either subcutaneous guselkumab 100 mg Q8W (n=113) or 200 mg Q4W (n=115) during the maintenance period, or placebo (n=58).
The primary endpoint of the study was combined fistula remission (assessed clinically and radiologically) at week 24, defined as complete closure of all external fistula openings, without development of new fistulas and drainage, and the absence of fluid collection >2 cm in the perianal fistulas as confirmed by MRI.
At week 24, the primary endpoint of combined fistula remission was achieved by 28.3 percent of patients in the guselkumab 100-mg group and 27 percent of those in the guselkumab 200-mg group compared with 10.3 percent of patients in the placebo group (p=0.007 and p=0.013, respectively). [DDW 2026, abstract 1058b]
Significantly more guselkumab-treated patients achieved a clinically assessed fistula response, defined as a ≥50-percent reduction in the number of open or draining perianal fistulas from baseline, as early as week 12 (24.6 percent [both dosing regimens] vs 12.1 percent; pnominal=0.041), which persisted through week 24 (32.7 percent; p=0.008 [100 mg] and 35.7 percent; p=0.003 [200 mg]) compared with placebo-treated patients. Peyrin-Biroulet noted that “this result is very interesting for our patients, because every month matters.”
Adverse events were consistent with the known safety profile of guselkumab. Its benefit-risk profile was favourable, with no new safety signals observed, he noted.
Overall, the study’s primary endpoint was met, according to Peyrin-Biroulet.
“The results from the FUZION study demonstrated the ability of guselkumab to achieve combined fistula remission. This is an exciting step forward for patients, expanding what’s possible for managing this debilitating and chronic condition,” the author noted.
Guselkumab induction and maintenance therapy was efficacious through week 24 in a study population with bio-naïve and -exposed patients with PFCD, he concluded.