Ustekinumab for fistulising perianal Crohn’s disease: a randomised placebo-controlled trial from the GETAID

Background Fistulising perianal Crohn’s disease (CD) remains a debilitating condition, with few randomised controlled trials conducted so far. Objective To evaluate the efficacy and safety of ustekinumab (UST) in patients with CD with active draining perianal fistulas ( NCT04496063 ) in a randomised placebo-controlled trial. Design In this double-blind, multicentre Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives trial, patients enrolled with active fistulising perianal CD were randomised 1:1 to receive UST (6 mg/kg intravenously at baseline followed by 90 mg subcutaneously at week 8, then every 8 weeks) or placebo, after standardised surgical management. The primary endpoint was combined clinical remission (absence of drainage from all external fistula openings) and radiological remission (absence of abscesses >2 cm on blinded central MRI) at week 12. At week 12, placebo non-responders could switch to UST, and UST non-responders could be intensified during the open-label phase. Results 32 patients were randomised (UST: 16; placebo: 16) across 10 French centres and 69% had prior anti-tumour necrosis factor failure. At week 12, combined remission was achieved in 62% with UST versus 25% with placebo (OR=5.1 (95% CI 1.07–24.4)). Clinical remission occurred in 62.5% vs 31% (OR=3.75 (95% CI 0.84 to 16.8)) and radiological remission in 87.5% vs 75% (OR=2.7 (95% CI 0.34 to 21.1)). Nine placebo-patients switched to UST during the open-label phase. Combined remission rates at week 48 were 50% in the placebo arm and 31% in the UST arm, respectively. Conclusion These findings suggest greater short-term clinical benefit with UST compared with placebo and support its use in patients with active fistulising perianal CD. Trial registration number NCT04496063 .