Key Facts
- Drug: guselkumab (Tremfya), IL-23 inhibitor
- Trial: phase 3 FUZION (NCT05347095)
- Indication: perianal fistulizing Crohn's disease
- Combined fistula remission: 28.3% (q8w) and 27.0% (q4w) vs 10.3% placebo
- Safety consistent with known profile
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Guselkumab Shows Efficacy in Perianal Fistulizing Crohn's Disease in Phase 3 FUZION Trial
The phase 3 FUZION trial found guselkumab achieved increased fistula remission rates than placebo in perianal fistulizing Crohn's disease.
Guselkumab (Tremfya) demonstrated significantly increased rates of combined fistula remission compared with placebo at week 24 in the phase 3 FUZION trial, marking what investigators describe as the first randomized controlled trial of an approved inflammatory bowel disease therapy to show efficacy in perianal fistulizing Crohn's disease in 2 decades. Johnson & Johnson announced the results on May 5, 2026, with the data presented as late-breaking findings at Digestive Disease Week (DDW) 2026.1
"The pain, swelling and persistent drainage associated with perianal fistulizing Crohn's disease can be profoundly disruptive to patients' daily lives," said Laurent Peyrin-Biroulet, MD, PhD, a study investigator and paid consultant for Johnson & Johnson. "Achieving durable fistula closure without repeated surgical interventions remains a significant unmet need."
What the Phase 3 FUZION Trial Showed
The FUZION study (NCT05347095) is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial evaluating guselkumab in adults with active perianal fistulizing Crohn's disease. 2 Eligible patients had one or more active draining perianal fistulas confirmed by blinded central MRI review, a Crohn's Disease Activity Index (CDAI) < 350, and inadequate response to conventional therapies or up to 2 advanced therapy classes. Patients were randomized in a 2:2:1 ratio to receive guselkumab 200 mg intravenously at weeks 0, 4, and 8 followed by either 100 mg subcutaneously every 8 weeks (q8w), 200 mg subcutaneously every 4 weeks (q4w), or placebo.
The primary endpoint, combined fistula remission at week 24, was defined as complete closure of all external fistula openings with no drainage, no development of new fistulas, and no evidence of underlying fluid collections on magnetic resonance imaging (MRI). This composite endpoint represents a stringent radiographic-clinical measure, requiring not only clinical closure but also confirmation of deep tissue healing on imaging.
Investigators observed combined fistula remission in 28.3% of patients in the 100 mg q8w group and 27.0% in the 200 mg q4w group, compared with 10.3% receiving placebo. Treatment differences were statistically significant for both dosing regimens (P = .007 and P = .013, respectively). Adverse events through 24 weeks were reported to be consistent with the known safety profile of guselkumab in Crohn's disease, though detailed safety data beyond this characterization were not disclosed in the announcement.1
Disease Burden and Unmet Need in Perianal Fistulizing Crohn's Disease
Perianal fistulizing disease affects nearly 25% of patients with Crohn's disease and represents one of its most disabling manifestations.3 In this disease, fistulas form when chronic inflammation drives ulceration through the full thickness of the bowel wall, creating abnormal channels between the intestine and the perianal skin or surrounding structures. Symptoms include persistent pain, swelling, drainage, recurrent abscess formation, and frequent need for surgical intervention, all of which carry significant quality-of-life consequences.
The last major randomized trial of an approved biologic in this specific population was conducted approximately 20 years ago, underscoring the longstanding evidence gap in this area. Remission rates remain low with existing approaches, and the stringent combined endpoint used in FUZION, requiring both clinical closure and MRI-confirmed absence of fluid collection, reflects the complexity of achieving meaningful disease control.
Guselkumab Mechanism and Regulatory History
Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 (IL-23) and is described as having dual-acting properties through additional binding to CD64, a receptor on IL-23-producing cells, although the clinical significance of this binding remains unknown and is based on in vitro data only.
The drug is currently approved in the United States for adults with moderately to severely active Crohn's disease, ulcerative colitis, moderate to severe plaque psoriasis, and active psoriatic arthritis, with pediatric indications in psoriasis and psoriatic arthritis for patients ≥ 6 years of age weighing ≥ 40 kg.
Limitations and Next Steps for Guselkumab in Fistulizing Crohn's Disease
The FUZION data as reported represent week-24 results; longer-term durability of fistula closure and maintenance of remission remain to be established. The press release did not include granular safety data, patient-reported outcome measures, or subgroup analyses. It is also worth noting that Peyrin-Biroulet, the quoted study investigator, is a paid consultant for Johnson & Johnson, which should be considered when interpreting his commentary. Johnson & Johnson has also announced the CHARGE study, described as the first head-to-head trial of IL-23 inhibitors in IBD, comparing guselkumab with risankizumab in Crohn's disease, with enrollment now open. 1
References
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. Press release. May 5, 2026. https://www.prnewswire.com/news-releases/johnson--johnson-study-shows-tremfya-guselkumab-is-the-first-and-only-il-23-inhibitor-to-demonstrate-efficacy-in-perianal-fistulizing-crohns-disease-302760610.html
ClinicalTrials.gov. A study of guselkumab in participants with fistulizing, perianal Crohn's disease (FUZION CD). NCT05347095. https://clinicaltrials.gov/study/NCT05347095?tab=researcher
Sulak A, et al. Where are we and where to next?—the future of perianal Crohn's disease management. J Clin Med. 2023;12(19):6379. doi:10.3390/jcm12196379
Spinelli A, Yanai H, Girardi P, et al. The impact of Crohn's perianal fistula on quality of life: results of an international patient survey. Crohns Colitis 360. 2023;5(3):otad036. doi:10.1093/crocol/otad036
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