Future studies should focus on subgroups of patients with Crohn’s disease treated with ustekinumab.
New research shows very little difference between treat-to-target strategies and standard-of-care therapy for patients with Crohn’s disease treated with ustekinumab.
A team, led by Silvio Danese, MD, PhD, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, assessed whether a treat-to-target approach with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity is advantageous for endoscopic improvement at week 48 compared to a clinically driven maintenance strategy for patients with Crohn’s disease.
Treat-to-target strategies are often advocated for some chronic disorders, including inflammatory bowel disease.
In the open-label, multicenter, randomized phase 3b STARDUST study, the investigators examined 440 adult patients with moderate-to-severe active Crohn’s disease that were treated with ustekinumab.
Each participant had a Crohn’s Disease Activity Index [CDAI] score of 220-450 and a Simple Endoscopic Score in Crohn’s Disease [SES-CD] of at least 3. Each patient received intravenous ustekinumab 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8.
In addition, at week 16 patients with a Crohn’s Disease Activity Index score improvement of at least 70 points was randomized to receive standard-of-care treatment (n = 221) or treat-to-target maintenance treatment (n = 219) through week 48.
Patients in the treat-to-target cohort received ustekinumab every 12 weeks or 8 weeks based on Simple Endoscopic Score in Crohn’s Disease improvements from baseline. The dosing could have escalated to every 4 weeks through week 48 if predetermined targets were missed.
In the standard-of-care arm, patients received ustekinumab every 8 or 12 weeks, with those who received treatment every 12 weeks able to escalate per European labeling.
The investigators sought primary efficacy endpoints of endoscopic response at week 48, defined as a SES-CD score of at least 50%, analyzed by non-responder imputation.
Overall, there was no significant difference in endoscopic response between the 2 groups (n = 83; 38% vs n = 66; 30%; P = 0.087). This was also true for endoscopic remission (n = 25; 11% vs n = 32; 15%; P = 0.334), mucosal healing (n = 31; 14% vs n = 37; 17%; P = 0.449), and clinical remission (n = 135; 62% vs n = 154; 70%; P = 0.072).
However, 1 difference did stand out. Clinical response was significantly lower in the treat-to-target group (n = 149; 68% vs n = 172; 78%; P = 0.020) compared to the standard-of-care group.
Other endoscopic, clinical, or biomarker outcomes were generally not significantly different between the 2 arms.
For safety, the most commonly reported treatment-emergent adverse events were nasopharyngitis (n = 29; 13%; n = 29; 13%), abdominal pain (n = 23; 11%; n = 19; 9%), arthralgia (n = 24; 11%; n = 19; 9%), and headache (n = 24; 11%; n = 21; 10%).
“Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone,” the authors wrote. “Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab.”
The study, “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,” was published online in The Lancet Gastroenterology & Hepatology.