Treatment with the sphingosine1-phosphate 1 (S1P) and 5 (S1P5) receptor modulator ozanimod led to clinical, endoscopic, and histologic remission in patients with moderate-to-severe ulcerative colitis (UC), data from the ongoing TOUCHSTONE study have shown, offering hopes for novel oral therapeutics with distinct mechanisms of action.
Ozanimod works by blocking lymphocyte egress from lymph nodes, inducing peripheral lymphocyte sequestration and preventing lymphocyte trafficking into the gastrointestinal tract in patients with UC.
At week 32, endoscopic and clinical remission (82.6 and 87.1 percent, respectively) were highly concordant with histological remission in colitis patients treated with ozanimod (n=197), but were less concordant with Patient Global Assessment (PGA, 75.8 percent), absence of diarrhoea, and rectal bleeding (65.2 percent). [AIBD 2016, abstract P-010]
“Ozanimod was effective in the induction of clinical, endoscopic and histologic remission at week 32 in patients with moderate-to-severe UC,” said study author Dr William Sandborn of the University of California San Diego and colleagues.
TOUCHSTONE was a randomized, double-blind, placebo-controlled phase II trial involving 197 patients with moderate-to-severe UC (Mayo clinic score, 6-12; endoscopic subscore, 2 or 3) who were randomized to ozanimod 1 mg or 0.5 mg vs placebo once daily for 8 weeks. Patients who achieved a clinical response at week 8 (n=103) continued with their original regimen through week 32 in a maintenance period. Ninety-one completed their dose. Those without a response were allowed to cross over to optional open-label treatment.
At baseline, histologic remission was comparable among the three groups. At weeks 8 and 32, patients treated with ozanimod 1 mg had greater histologic improvement (p=0.0345 and p=0.0033, respectively) vs those taking placebo.
At week 8, histologic remission occurred in 22.4 percent of the 1 mg cohort (p=0.0705), 13.8 of the 0.5 mg cohort (p=0.6294), and 10.8 percent of the placebo cohort. At week 32, histologic remission rates were 31.3 percent (p=0.0006) 23.1 percent (p=0.0164), and 7.7 percent, respectively.
Oral formulations such as ozanimod hold great promise for the treatment of UC. However, more studies are warranted to establish ozanimod’s safety in the long term. The drug has recently entered two phase III trials – the first will assess ozanimod as an induction/and maintenance therapy for up to 52 weeks in patients with UC while the second is an open label extension study in patients, with up to 5 years of follow-up.