Stelara Leads to High Clinical Response, Remission in Severely Active Crohn’s, Phase 3 Study Shows

Stelara Leads to High Clinical Response, Remission in Severely Active Crohn’s, Phase 3 Study Shows

Almost 80% of patients with severely active Crohn’s disease (CD) responded to treatment with Stelara (ustekinumab) and two-thirds achieved clinical remission, according to 16-week results from a Phase 3 clinical trial.

The results were presented at the 15th Congress of the European Crohn’s & Colitis Organization (ECCO) in an he abstract titled, “Intestinal ultrasound response and transmural healing after ustekinumab induction in Crohn’s disease: Week 16 interim analysis of the STARDUST trial substudy.”

Stelera, developed by Janssen Pharmaceuticals, part of Johnson & Johnson, is approved in the U.S. for the treatment of adults patients with moderately to severely active CD and moderately to severely active ulcerative colitis, the main types of inflammatory bowel disease (IBD), as well as other inflammatory diseases.

The biologic agent works by inhibiting two pro-inflammatory proteins, interleukin (IL)-12 and IL-23, both of which are highly expressed in IBD.

The Phase 3b STARDUST (NCT03107793) study is a randomized, international, clinical trial designed to evaluate the effectiveness of two treatment strategies: treat-to-target (T2T) maintenance treatment strategy and standard of care.

T2T is a proactive treatment strategy in which frequently monitored outcomes — such as endoscopic response, biomarkers and clinical symptoms — help guide use of the medication.

The primary endpoint was the proportion of patients that had an endoscopic response — defined as a greater than or equal to 50% reduction in simple endoscopic score for Crohn’s disease (SES-CD) — after 48 weeks.

The clinical trial was conducted with 500 participants, each of whom received one intravenous (IV) dose of 6 mg/kg of Stelara, followed by a 90 mg Stelara injection at week 8.

At week 16, patients who had a greater than or equal to 70-point (CDAI70) reduction in Crohn’s Disease Activity Index (CDAI) score were randomized to either a treat-to-target or standard-of-care group and followed up to week 48.

Among the 220 CDAI70 patients who were randomized to the treat-to-target arm, 37% achieved endoscopic response at week 16. There is no data available on patients in the standard-of-care group, as endoscopy at week 16 was measured only in the treat-to-target group.

“Crohn’s disease patients may respond to treatment while continuing to experience internal inflammation that can cause irreversible damage,” Silvio Danese, MD, PhD, head of the Inflammatory Bowel Diseases Center at Humanitas Research Hospital in Milan, said in a press release. “These patients may benefit from a more proactive, robust treatment approach and less invasive monitoring methods.”

STARDUST is the first study of the treat-to-target strategy for CD using endoscopic response to guide treatment. It is also the first study to use intestinal ultrasound (IUS) to monitor CD patients in a clinical trial.

IUS is based on evaluating bowel features, such as the thickness of the bowel wall and presence of hypervascularization (an increased number or concentration of blood vessels).

The 16-week data showed that the safety profile for Stelara in STARDUST was consistent with the established safety profile observed in other Phase 3 IBD clinical trials, as well as that seen in other indications.

There was a 79% clinical response rate and 67% clinical remission rate, and treatment with Stelara at week 16 was also associated with IUS response that was identified as early as week 4.

However, additional studies need to confirm whether an early IUS response at week 4 is predictive of long-term clinical and endoscopic outcomes for CD patients.

“I am encouraged by these data, [which] demonstrate the potential clinical utility of the noninvasive IUS method in helping guide treatment of CD and look forward to forthcoming data that may help us better understand the possible benefits of a treat-to-target strategy,” Danese said.

STARDUST represents a significant milestone in our commitment to helping Crohn’s disease patients and the physicians who treat them,” said Jan Wehkamp, MD, vice president of Janssen Research & Development. “The data from this study may provide us with key clinical insights which may inform future treatment strategies.”