After 44 weeks of maintenance therapy, endoscopic improvement was observed in 43.6% and 51.1% of patients treated with the study drug q12w and q8w, respectively.
Ustekinumab (Stelara) recently received United States Food and Drug Administration (FDA) approval to treat patients with moderate to severely active ulcerative colitis (UC). Administered as a single intravenous (IV) infusion, followed by subcutaneous injections for maintenance, it is the first and only approved UC treatment to demonstrate improvement of the colon. Previously, it was unknown whether the maintenance treatment affected mucosal healing resulting in endoscopic and histologic improvement.
As part of the phase 3 UNIFI trial of ustekinumab for patients with UC, investigators evaluated the effects of the maintenance regimen on histologic and endoscopic activity. Their results were presented at the American College of Gastroenterology’s Annual Scientific Meeting (ACG 2019) in San Antonio, Texas, and presenting author William Sandborn, MD, chief of the division of gastroenterology at University of California, San Diego, and clinical trial investigator, discussed the results of the study with MD Magazine®.
Data from 961 patients were included in the analysis. Those who demonstrated response 8 weeks after receiving the initial IV loading dose were then randomized to receive a maintenance regimen of either subcutaneous ustekinumab 90 mg or placebo every 8 (q8w) or 12 weeks (q12w).
Endoscopic improvement was defined as a Mayo endoscopy subscore < 1, and histologic improvement was defined as displaying the following Geboes score-based criteria: absence of erosions or ulcerations, absence of crypt destruction, and < 5% of crypts with neutrophil infiltration. Histo-endoscopic mucosal healing was defined as achievement of both endoscopic and histologic improvement.
Investigators collected 2 colonic biopsies from the distal colon at screening, as well as at Weeks 0 and 44 of the maintenance regimen.
After 44 weeks of maintenance therapy, endoscopic improvement was observed in 43.6% and 51.1% of patients treated with the study drug q12w (p=0.002 vs placebo) and q8w (p< 0.001), respectively, compared with 28.6% in the placebo arm. At week 44, histologic improvement was achieved in 32.9%, 54.0%, and 59.3% of patients treated with placebo, ustekinumab q12w, and ustekinumab q8w, respectively (p< 0.001 for both q12w and q8w).
A total of 24.1%, 38.8%, and 45.9% of patients treated with placebo, ustekinumab q12w (p=0.002), and ustekinumab q8w (p=0.001) achieved histo-endoscopic mucosal healing, respectively.
Overall, histologic improvement demonstrated at week 44 was significantly associated with endoscopic improvement and mucosal healing (p< 0.001). The achievement of both endoscopic and histologic improvement after 8 weeks of ustekinumab treatment was associated with clinical remission and steroid-free clinical remission at week 44 (p< 0.05).
“Among patients with moderately-to-severely active UC, those receiving [subcutaneous ustekinumab] maintenance had higher rates of [endoscopic improvement], [histologic improvement], and [mucosal healing] than those receiving placebo,” the research team concluded. “Both [endoscopic improvement] and [histologic improvement] are associated with subsequent clinical remission and steroid-free clinical remission.”
The study, Effects of Ustekinumab Maintenance Therapy on Endoscopic Improvement and Histologic Improvement in the UNIFI Phase 3 Study in Ulcerative Colitis, was presented Wednesday, October 30, 2019, at the American College of Gastroenterology Annual Scientific Meeting (ACG 2019) in San Antonio, Texas.