A Treat-to-Target Approach With Ustekinumab May Be Effective Among Some Patients With Crohn Disease

Crohn illness and intestine disease or crohns medical concept as human digestive colon with inflammation symptoms causing obstruction as a 3D illustration.
Investigators assessed the safety and efficacy of a treat-to-target strategy with ustekinumab dose escalation in patients with active Crohn disease.

Ustekinumab escalation using a treat-to-target strategy did not improve endoscopic outcomes among all patients with Crohn disease (CD) but may have some efficacy among certain subgroups. These findings, from an open-label, multicenter, randomized, phase 3b trial, were published in The Lancet Gastroenterology and Hepatology.

Patients (N=498) with moderate to severe CD were recruited at centers in 12 European countries for the STARDUST trial (ClinicalTrials.gov Identifier: NCT03107793). During an induction phase, patients received 6 mg/kg intravenous ustekinumab at baseline and 90 mg subcutaneous ustekinumab at week 8. Responders (n=440) were randomly assigned at week 16 to receive a treat-to-target (n=219) or standard-of-care (n=221) dosing strategy.

The primary endpoint was endoscopic response at week 48. For the treat-to-target strategy, patients who had <25% improvement were treated every 8 weeks starting at week 16 and those with ³25% improvement received treatment every 12 weeks starting at week 20.

The intervention and control cohorts were 52% and 50% women, aged median 36.0 (IQR, 27.0-48.0) and 34.0 (IQR, 25.0-47.0) years, body mass index was 23.05 (IQR, 20.28-26.85) and 23.36 (IQR, 20.70-26.01) kg/m2, 98% and 96% were taking ³1 concomitant medication, and 84% and 77% had uncomplicated CD, respectively.

Among the intervention cohort, 59% initially received ustekinumab every 12 weeks and 60% remained on that therapy through week 48. The remaining patients received therapy every 8 weeks and 40% remained on that schedule.

Endoscopic response was achieved by 38% of the treat-to-target and 30% of the standard-of-care recipients (P =.087). Using a last observation carried forward approach, more patients in the treat-to-target cohort achieved endoscopic response at week 48 (40% vs 31%; P =.046). Similarly, treat-to-target was favored for endoscopic response in the modified nonresponder imputation analysis (43% vs 32%; P =.036).

Fewer treat-to-target recipients exhibited a Crohn Disease Activity Index (CDAI-70) improvement response (adjusted treatment difference, -8.5; 95% CI, -16.7 to -0.4; P =.042).

In a subgroup analysis, treat-to-target was favored for patients with longer duration (greater median) disease (odds ratio [OR], 2.15; 95% CI, 1.17-3.94; P =.013) and among those who were older (greater median age; OR, 1.82; 95% CI, 1.00-3.31; P =.050).

Adverse events were reported by 86% of the treat-to-target and 81% of the standard care cohorts. Discontinuation due to adverse events occurred among 5% and 9% of patients, respectively.

This study was limited by its open-label design and by the fact that more patients in the intervention group (4%) refused the 16-week endoscopy.

This study found that a treat-to-target approach had similar outcomes as a standard-of-care approach for the treatment of moderate to severe CD using ustekinumab. However, among some patient groups, this treatment strategy may be more effective and warrants further analysis.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Danese S, Vermeire S, D’Haens G, et al. Treat to target versus standard of care for patients with Crohn’s disease treated with ustekinumab (STARDUST): an open-label, multicentre, randomised phase 3b trial. Lancet Gastroenterol Hepatol. Published online February 1, 2022. doi:10.1016/S2468-1253(21)00474-X