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The Janssen Pharmaceutical Companies of Johnson & Johnson announced new data showing treatment with a single intravenous (IV) dose of Stelara (ustekinumab) induces clinical remission and response in adults with moderate to severe ulcerative colitis (UC) who previously experienced an inadequate response or were intolerant to conventional or biologic therapies. 

Results from the induction phase of the Phase 3 UNIFI study show that treatment with a single IV dose of Stelara induced clinical remission in a significantly greater proportion of UC patients at week 8, compared with placebo, at both doses studied. Major secondary endpoints including the proportion of patients in clinical response, endoscopic healing, as well as improvement in health-related quality of life, were also significantly higher at week 8 among patients receiving Stelara compared with patients receiving placebo. About 50 percent of study participants are considered biologic refractory, and 17 percent have a history of inadequate response or intolerance to an anti-TNF and/or Entyvio (vedolizumab).

"Ulcerative colitis is a complex immune disease, and more than half of UC patients have not experienced remission with currently available conventional or biologic treatment options," said lead investigator Bruce E. Sands, MD, Dr. Burrill B. Crohn professor of medicine and chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai. "The significant rates of remission observed through the 8-week induction, coupled with a safety profile that is well-documented through years of research and use in other immune diseases, demonstrate the potential for ustekinumab as an effective treatment for UC."

Patients participating in the Phase 3 UNIFI study were randomized 1:1:1 at week 0 and received a single IV dose of placebo, Stelara 130 mg, or Stelara ~6 mg/kg (weight tiered dosing: patients weighing less than or equal to 55 kg received 260 mg; patients weighing more than 55 kg and less than or equal to 85 kg received 390 mg; and patients weighing more than 85 kg received 520 mg). At week 8, patients (n=961) were evaluated for clinical remission, endoscopic healing, clinical response, change from baseline in the IBDQ score, and mucosal healing (an endpoint that includes both endoscopic healing and histologic healing).

At week 8:

  • 15.6 percent of patients receiving Stelara 130 mg and 15.5 percent of patients receiving Stelara ~6 mg/kg achieved clinical remission compared with 5.3 percent of patients receiving placebo (p < 0.001). Remission was defined as a Mayo score ≤2 points, with no individual subscore >1.
  • 26.3 percent of patients receiving Stelara 130 mg and 27 percent of patients receiving Stelara ~6 mg/kg experienced endoscopic healing compared with 13.8 percent of patient receiving placebo (p<0.001). Endoscopic healing was defined as a Mayo endoscopy subscore of 0 (normal mucosa or inactive disease) or 1 (mild disease activity).
  • 51.3 percent and 61.8 percent of patients receiving Stelara 130 mg and Stelara ~6 mg/kg achieved clinical response compared with 31.3 percent of patients receiving placebo (p < 0.001). Clinical response was defined as a decrease from baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1.
  • 20.3 percent and 18.4 percent of patients receiving Stelara 130 mg and Stelara ~6 mg/kg achieved mucosal healing compared with 8.9 percent of patients receiving placebo (p < 0.001). Mucosal healing is defined as combined endoscopic healing (Mayo endoscopy subscore of 0 or 1) and histologic healing (defined as 0-<5% neutrophils in epithelium, no crypt destruction, and no erosions or ulcerations or granulations).

In addition, both doses of STELARA resulted in statistically significant improvements in the Inflammatory Bowel Disease Questionnaire (IBDQ), a health-related quality of life measure for patients with IBD, as well as markers of inflammation, including C-reactive protein (CRP), fecal lactoferrin and calprotectin.

Through week 8, adverse events (AEs), serious AEs and infections (including serious infections) were reported in similar proportions across Stelara and placebo treatment groups. No malignancies, opportunistic infections or tuberculosis were reported through week 8. One death from an esophageal varices hemorrhage was reported for a patient with no known history of cirrhosis or portal hypertension in the ~6mg/kg dose group prior to week 8.

"Stelara is the first biologic approved for any indication that targets interleukin (IL)-12 and IL-23 cytokines, which are believed to play a role in immune-mediated diseases, like ulcerative colitis," said Philippe Szapary, MD, MSCE, VP, clinical development, Janssen Research & Development, LLC. "These induction data from the Phase 3 UNIFI study underscore the potential for this pathway in the treatment of UC, which may lead to a new effective and safe treatment option for UC patients in the future."

In addition to the UNIFI study data, Janssen is also presenting results from the IM-UNITI open label long-term extension (LTE) for Stelara in the treatment of adults with moderate to severe Crohn's disease, including an oral presentation on long-term efficacy of Stelara with and without concomitant immunosuppressants through 2 years. A poster demonstrating the long-term efficacy and safety of STELARA through 3 years of treatment will also be presented.

About the UNIFI Trial 
UNIFI is a Phase 3 protocol designed to evaluate the safety and efficacy of Stelara induction and maintenance dosing for the treatment of moderate to severe ulcerative colitis in adults who demonstrated an inadequate response to or were unable to tolerate conventional (i.e., corticosteroids, immunomodulators) or biologic (i.e., one or more TNF blockers or vedolizumab) therapies.

Both the induction and maintenance studies are randomized, double-blind, placebo-controlled, parallel group, multi-center studies The Induction study was of at least 8 weeks duration for each participant. Participants achieving clinical response in the Induction study were eligible for the Maintenance study. The Maintenance study was 44 weeks duration. The primary endpoint of the induction study is clinical remission at week 8 and the primary endpoint for the maintenance study is clinical remission at week 44 among responders to a single IV Stelara infusion.

After completion of the maintenance study, a long-term extension will follow eligible participants for an additional 3 years.

(Source: The Janssen Pharmaceutical Companies of Johnson & Johnson)

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