TREMFYA - Use in Adult Patients with Fistulizing Crohn's Disease

SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 3 randomized clinical trial is ongoing to evaluate the efficacy and safety of TREMFYA in fistulizing, perianal Crohn’s disease (CD). Results up to week 24 are reported below. Additional details are available at clinicaltrials.gov: NCT05347095.^1,2

clinical data

FUZION Study

FUZION (NCT05347095) is a phase 3, randomized, double-blind, placebo (PBO)-controlled, multicenter study evaluating the efficacy and safety of TREMFYA in adult patients with active perianal fistulizing CD.²

Study Design/Methods

• Patients enrolled in this study met the following criteria:
  • Adults with ≥1 active draining perianal fistula confirmed by blinded central magnetic resonance imaging (MRI) review
  • Crohn’s Disease Activity Index (CDAI) <350
  • Intolerance or an inadequate response to oral corticosteroids, 6-mercaptopurine, azathioprine, methotrexate, or up to 2 advanced-therapy classes (anti-tumor necrosis factor [TNF] agents, vedolizumab, or Janus kinase inhibitors [JAKi]) and be refractory to antibiotics (i.e., ciprofloxacin and metronidazole)
• The study design is presented in Figure: FUZION Study Design.

• The primary endpoint was the combined fistula remission at week 24.
  • Combined fistula remission was defined as: (1) clinically assessed fistula remission: 100% closure of all treated external openings with no new fistulas or abscesses and no drainage from external openings (either spontaneous or upon gentle finger compression); and (2) radiologically assessed fistula remission: absence of perianal fistula collections >2 cm, as confirmed by blinded central review of MRI results.
• Multiplicity-controlled secondary endpoints were clinically assessed fistula remission at week 24 and clinically assessed fistula response (defined as a ≥50% reduction from baseline in the number of open or draining perianal fistulas) at week 24.
• The key secondary endpoint was clinically assessed fistula response at week 12.

Results

• Among 286 patients in the full analysis set, 113 received TREMFYA 100 mg SC Q8W, 115 received TREMFYA 200 mg SC Q4W and 58 received PBO; 91.3% completed 24 weeks of therapy. 
• Baseline characteristics are summarized in Table: Demographics and Baseline Characteristics - FUZION Study.

Efficacy

• At week 24, significantly greater proportions of patients treated with TREMFYA achieved the primary endpoint and secondary endpoints at week 24 vs PBO. See Figures: Primary Endpoint: Combined Fistula Remission at Week 24 and Multiplicity-Controlled Secondary Endpoints: Clinically Assessed Fistula Remission and Clinically Assessed Fistula Response at Week 24.

• Clinically assessed fistula response through week 24 is depicted in Figure: Clinically Assessed Fistula Response through Week 24.

Safety

• Through week 24, no opportunistic infections, anaphylactic or serum sickness reactions, major adverse cardiovascular event, clinically important hepatic disorders, venous thromboembolic events, or deaths were reported; 1 case of B-cell lymphoma (assessed by the investigator as unrelated to study treatment) occurred.
• All injection-site reactions were mild and did not result in treatment discontinuation.
• For adverse events, see Table: Summary of AEs through Week 24.

Case Report

Croitoru et al (2022)¹ described the case of a 43-year-old male patient with a history of fistulizing CD and who was referred for suspected hidradenitis suppurativa (HS).

• The patient was diagnosed with CD due to a 5-year presentation of weight loss and diarrhea, confirmed by endoscopic assessment. His CD progressed to pancolitis involving the rectum with multiple draining fistulas.
• After failing multiple treatments, including antibiotics, mesalamine, azathioprine, and various TNF inhibitors, he underwent surgical intervention initially with loop ileostomy, but his perianal disease continued to persist.
• Over the next year, the patient was treated with ustekinumab but developed pancolitis. This led to initiation of methylprednisolone treatment, bridged to a modified total proctocolectomy with end ileostomy. Perianal dissection was foregone, and a small stump was left in place.
• Over the following months, the patient was put on steroid taper and later treated with a TNF inhibitor. Addition of sulfasalazine, methotrexate, hyperbaric oxygen, and concurrent intralesional steroids minimally benefited.
• The arrangement of draining tract and inflammatory nodules led to suspicion for concomitant HS and the patient was referred to dermatology clinic for evaluation and management.
  • Upon further examinations, there were deep ulcerated fissures in the bilateral groin with linear sinuses with peripheral erosions and fibrinoid changes at the wound. There were also many tender and deep nodules and subcutaneous abscesses adjacent ulcers, which extended perianally. The patient described ongoing weight loss, without fever, and abdominal pain and minimal change in stoma output.
  • Given the patient's history of fistulizing CD and extensive wounds, it was suspected that he had ongoing occult inflammatory intestinal disease and fistulation to skin. MRI of the pelvis showed an intramural abscess in the most superior aspect of the rectal stump and multiple emanating fistulas.
  • Treatment with ertapenem drastically reduced perianal pain and discharge and the patient was subsequently started on TREMFYA 100 mg every 8 weeks.
  • Within 6 months of initiating TREMFYA, the patient experienced near complete resolution of all inflammatory nodules and abscesses with significant weight gain and improvement of the bilateral perineal ulcerations to near resolution. His serum C-reactive protein levels decreased from baseline (60 to 8.3).
  • Repeated MRI of the pelvis and abdomen showed interval resolution and improvement of multiple intestinal fistulas with reduction in size of intramural abscess. The patient underwent multidisciplinary re-evaluation for surgical candidacy to remove the remaining portion of his rectal stump.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 12 August 2026.