ORLANDO — Ozanimod induced clinical, endoscopic and histologic remission in patients with ulcerative colitis, and all three of these endpoints were highly correlated, according to a poster presented at AIBD 2016.
Ozanimod (RPC1063, Receptos) is an investigational, oral, small molecule sphingosine 1-phosphate 1 and 5 receptor modulator in development for inflammatory bowel disease and other immune-inflammatory indications.
William J. Sandborn
“Histologic remission at week 32 following treatment with ozanimod was highly concordant with mucosal healing and clinical remission, and less concordant with the individual stool frequency and rectal bleeding scores,” William J. Sandborn, MD, professor of medicine, chief of the division of gastroenterology and director of University of California San Diego Inflammatory Bowel Disease Center, told Healio Gastroenterology. “Histologic remission is achievable with ozanimod and may be a future treatment goal in ulcerative colitis.”
In the phase 2 TOUCHSTONE trial, Sandborn and colleagues randomly assigned 197 patients with UC to receive 1 mg or 0.5 mg of ozanimod or placebo. At weeks 8 and 32, a significantly greater proportion of patients achieved clinical remission, response, and endoscopic mucosal healing with the 1 mg dose of ozanimod.
The investigators then evaluated whether ozanimod leads to histologic improvement and healing by assessing biopsies collected at baseline and weeks 8 and 32, which were scored from 0 to 22 using the Geboes score. Histologic remission was defined as a Geboes score of less than two.
At baseline, the mean Geboes score was 12.92 in the 1-mg group, 14.36 in the 0.5-mg group and 13.94 in the placebo group, which were comparable.
The 1-mg group had greater histologic improvement compared with the placebo group at week 8 (P = .0345), and at week 32 (P = .0033), while the 0.5-mg group showed numerical but not significant improvements compared with placebo at both time points.
At week 8, 22.4% of the 1-mg group achieved histologic remission compared with 10.8% of the placebo group (P = .0705), while 13.8% of the 0.5-mg group achieved histologic remission at this time point.
At week 32, 31.3% of the 1-mg group achieved histologic remission (P = .0006 vs. placebo), as did 23.1% of the 0.5-mg group (P = .0164 vs. placebo), and 7.7% of the placebo group.
Notably, endoscopic (87.1%) and clinical remission scores (82.6%) were “highly concordant” with histologic remission at week 32 in both ozanimod dose groups. There was high concordance between endoscopic and histologic remission at this time point in both the 1-mg (83.6%) and 0.5-mg groups (90.8%).
Most (86.1%) ozanimod-treated patients in histologic remission were also in endoscopic remission (86.1%), and among ozanimod-treated patients in endoscopic remission, 72.1% were also in histologic remission.
Finally, histologic remission showed concordance with normalized Patient Global Assessment (75.8%), absence of diarrhea (73.5%) and rectal bleeding (65.2%).
“Ozanimod was effective in the induction of clinical, endoscopic, and histologic remission at week 32 in patients with moderate to severe UC [and] histologic remission at week 32 following treatment with ozanimod is highly concordant with endoscopic and clinical remission,” Sandborn and colleagues wrote. – by Adam Leitenberger
Sandborn WJ, et al. Abstract P-010. Presented at: Advances in Inflammatory Bowel Diseases; Dec. 8-10, 2016; Orlando, Fla.
Disclosures: Sandborn reports financial relationships with Celgene, Receptos and numerous other financial relationships and patents.