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.