First randomised T2T trial using endoscopy to guide dose escalation

STARDUST is the first randomised treat-to-target (T2T) trial using endoscopy at week 16 to guide dose escalation in patients with Crohn’s disease [1]. After 48 weeks maintenance therapy with ustekinumab, a numerically higher proportion of patients achieved an endoscopic response in the T2T versus standard-of-care arm. Hence, T2T could be an additional tool for physicians to guide ustekinumab dosing decisions in Crohn’s disease.

T2T has been proposed as an effective strategy to optimise management of Crohn’s disease. The phase 3b STARDUST trial compared a T2T maintenance strategy with standard-of-care in 500 patients with active, moderate-to-severe Crohn’s disease who failed conventional therapy and/or 1 biologic.

Patients received intravenous, weight-based ustekinumab (~6mg/kg) at week 0 (baseline) and thereafter subcutaneous ustekinumab 90 mg at week 8. At week 16, CDAI 70 responders were randomised 1:1 to the T2T or standard-of-care arm. Patients in the T2T arm were assigned to subcutaneous ustekinumab every 12 or 8 weeks based on 25% improvement in Simple Endoscopic Score in Crohn’s disease (SES-CD) score versus baseline. From week 16-48, ustekinumab dose was increased up to every 4 weeks if the following targets were not met: CDAI <220 and ≥70-point improvement from baseline, and C-reactive protein ≤10mg/L or faecal calprotectin ≤250µg/g.

The current analysis evaluated endoscopic and clinical results after 48 weeks. A numerically higher proportion of patients in the T2T achieved the primary endpoint, namely ≥50% reduction in SES-CD versus baseline, at week 48 compared with the standard-of-care arm: 37.7% versus 29.9% (P=0.0933; non-responder imputation [NRI]). A statistically significant difference was reached in a sensitivity analysis: 40.0% T2T versus 30.8% standard-of-care (P=0.0494; last observation carried forward [LOCF]).

At week 48, high clinical response rates were achieved in both arms:

• T2T 68.2% versus standard-of-care 77.8% (P=0.02; NRI);
• T2T 89.5% versus standard-of-care 89.6% (P>0.05; LOCF).

Furthermore, high biomarker responses were achieved in T2T versus standard-of-care regarding improvement of ≥50% in faecal calprotectin (39.4% versus 46.5% (P>0.05; NRI); and 63.1% versus 60.6% (P>0.05; LOCF)) and C-reactive protein (41.7% versus 53.3% (P=0.032; NRI); and 53.2% versus 57.2% (P>0.05; LOCF)). No new safety signals were reported.

The current results suggest that T2T could be an additional tool for physicians to guide ustekinumab dosing decisions in Crohn’s disease.

 

1. Danese S. Clinical and endoscopic response to treat-to-target versus standard of care in Crohn's disease patients treated with ustekinumab: week 48 results of the STARDUST trial. UEG Week Virtual 2020, abstract LB11.

Posted on 2 November, 20208 April, 2024