Guselkumab (Tremfya) showed higher 24-week fistula remission than placebo in adults with perianal fistulizing Crohn disease.
Johnson & Johnson reported late-breaking Phase 3 data at Digestive Disease Week 2026 indicating that guselkumab (Tremfya) achieved higher rates of combined fistula remission than placebo at 24 weeks in adults with active perianal fistulizing Crohn disease.1 The finding is notable for clinical trial operations and inflammatory bowel disease investigators because randomized controlled data in this specific Crohn disease phenotype have been limited, despite its substantial morbidity and frequent need for multidisciplinary care.2,3
“The pain, swelling and persistent drainage associated with perianal fistulizing Crohn’s disease can be profoundly disruptive to patients’ daily lives,” study investigator Laurent Peyrin-Biroulet, MD, PhD, said in the company announcement. He added that durable fistula closure without repeated surgical intervention remains a major unmet need.1
The randomized, placebo-controlled, double-blind, multicenter FUZION study (NCT05347095) enrolled adults with one or more active draining perianal fistulas confirmed by blinded central MRI review, Crohn Disease Activity Index scores less than 350, and inadequate response to conventional therapies or as many as 2 advanced therapy classes.1,4 Patients were assigned in a 2:2:1 ratio to guselkumab 200 mg IV at weeks 0, 4, and 8 followed by either 100 mg subcutaneously every 8 weeks or 200 mg subcutaneously every 4 weeks, or placebo.1,4
The primary endpoint was combined fistula remission at week 24, defined as complete closure of all external openings with no drainage, no new fistulas, and no evidence of underlying fluid collections on MRI.1 In the sponsor’s report, remission rates were 28.3% with guselkumab 100 mg every 8 weeks and 27.0% with guselkumab 200 mg every 4 weeks, compared with 10.3% for placebo; both comparisons were statistically significant (P = .007 and P = .013, respectively).1
The company said adverse events through 24 weeks were consistent with the known safety profile of guselkumab in Crohn disease, but detailed event rates were not disclosed in the announcement.^1
For clinical teams, the MRI-based composite endpoint is relevant because perianal fistula trials have been challenged by variability in definitions of response and the limitations of external drainage assessment alone. A combined clinical-radiologic endpoint may offer a more stringent and operationally reproducible measure, although full interpretation will depend on the complete dataset, including baseline anatomy, concomitant surgical management, seton use, and durability beyond 24 weeks.
Perianal fistulizing disease affects roughly 1 in 4 patients with Crohn disease and is associated with pain, drainage, abscess formation, impaired quality of life, and repeated procedures.2,3 Management typically combines medical and surgical approaches, with anti-tumor necrosis factor therapy historically serving as the principal biologic option with supportive randomized evidence for fistula closure. Even so, remission remains difficult to sustain, and recurrence is common.2
Guselkumab was the first FDA-approved, fully-human, dual-acting monoclonal antibody to block interleukin (IL)-23—a significant driver of the pathogenesis of inflammatory diseases—by attaching to the p19 subunit of IL-23 and to CD64, a receptor on cells that produce IL-23. The drug is indicated to treat adult patients with moderate to severe plaque psoriasis who may benefit from systemic therapy or phototherapy; for adult patients with active psoriatic arthritis; and most recently for adult patients with moderately to severely active ulcerative colitis.
The role of guselkumab in luminal Crohn disease has been supported by regulatory review and prior Phase 3 development, but perianal fistulizing disease has remained a distinct evidence gap because patients with complex fistulas are often underrepresented or analyzed separately in registrational programs.1
The new signal should be interpreted cautiously until peer-reviewed publication or full congress presentation materials provide additional granularity. Important unanswered questions include comparative effectiveness versus anti-tumor necrosis factor agents, outcomes in biologic-exposed subgroups, need for concomitant antibiotics or surgery, and maintenance of remission after week 24.
For trial operators, the study also underscores the feasibility of enrolling a narrowly defined fistulizing Crohn population using central MRI confirmation, a design element that may influence future protocol development in this space.4
Johnson & Johnson also said it is opening enrollment for CHARGE, a head-to-head study comparing guselkumab with risankizumab in Crohn disease, although that study is not specific to perianal fistulizing disease.1 Whether the FUZION results ultimately affect labeling, guidelines, or treatment sequencing will depend on regulatory review and the availability of complete efficacy and safety data.
