Extension studies highlight ozanimod safety in moderate-to-severe UC
An analysis of patients with moderately to severely active ulcerative colitis (UC) highlighted the general safety of the oral sphingosine-1-phosphate (S1P) receptor 1 and 5 modulator ozanimod, according to a presentation at Digestive Disease Week 2021.
“Long-term treatment with ozanimod in patients with moderately to severely active UC has a manageable safety profile, consistent with the known safety profile for ozanimod, with no unexpected safety concerns or new safety signals,” said study author Professor Geert D’Haens from Amsterdam University Medical Centers, Amsterdam, the Netherlands, and co-authors.
Participants were individuals aged 18–75 years with moderately to severely active UC on stable doses of oral aminosalicylates, prednisone, or budesonide enrolled in the TOUCHSTONE and True North studies and their respective open-label extensions (OLE).
Participants in the phase II TOUCHSTONE study completed a 9-week induction and 24-week maintenance phase during which time they were randomized to receive ozanimod or placebo. Non-responders at week 9 and those who completed or relapsed during the maintenance phase could enrol in the OLE where they received ozanimod 1 mg for ≤6 years. In the phase III True North trial, participants were randomized to receive ozanimod or placebo during the 10-week induction and 42-week maintenance phases. Week 10 non-responders, patients who completed or relapsed during the maintenance phase, and those who completed ≥1 year in the TOUCHSTONE OLE phase received ozanimod 1 mg in the ongoing True North OLE.
The pooled analysis population comprised 1,158 patients (mean age 41.6 years) who had received ozanimod 1 mg for a median 65.79 weeks and 508 patients (mean age 42.4 years) who had received placebo for a median 17.21 weeks, amounting to 1,841.7 and 242.8 patient-years (PYs) of exposure, respectively. Of these, 716 and 322 patients had been on ozanimod 1 mg for ≥1 and ≥2 years, respectively. About 59 percent of the patients were male and about 90 percent were White. About 93 and 95 percent of ozanimod and placebo recipients were on concomitant medication, with 35.8 and 28 percent, respectively, on systemic corticosteroids.
During the pooled controlled induction period (496 and 281 patients in the ozanimod and placebo groups, respectively), treatment-emergent adverse event (TEAE) rates were similar between groups (37.9 percent vs 36.3 percent).
In the overall pooled population, TEAEs occurred in 68.7 and 40.7 percent of the ozanimod and placebo groups, respectively, translating to an incident rate (IR) of 94.9 and 112.1 per 100 PYs, respectively. Lymphopenia and decreased lymphocyte count occurred in ozanimod recipients (8.9 and 6.1 percent, respectively), with no incidence in placebo recipients. Other frequently occurring (≥5 percent of ozanimod recipients) TEAEs with ozanimod vs placebo were nasopharyngitis (7.4 percent vs 2.0 percent), anaemia (7.3 percent vs 4.1 percent), increased alanine aminotransferase levels (6.2 percent vs 0.4 percent), headache (6.0 percent vs 1.6 percent), arthralgia (5.4 percent vs 2.4 percent), and upper respiratory tract infection (5.1 percent vs 2.2 percent).
The incidence of bradycardia and macular oedema/cystoid macular oedema was low, with five ozanimod recipients experiencing each. There were no incidents of symptomatic bradycardia warranting treatment. Pulmonary events were reported in 10 patients and hepatic effects in 150 patients.
“Pulmonary events were reversible and not progressive [and] hepatic enzyme elevations were generally asymptomatic, resolved with continued treatment, and did not lead to severe drug-induced liver injury,” said D’Haens.
Twelve ozanimod and two placebo recipients experienced malignancies.
Infections occurred in 29.1 and 14.0 percent of patients in the ozanimod and placebo groups, respectively, with serious infections occurring in 2.2 and 1.4 percent, respectively. Herpes zoster occurred in more ozanimod than placebo recipients (2.2 percent vs 0.4 percent), though none were disseminated or serious events.
“Exposure-adjusted IRs of AEs across the pooled study groups was lower in patients treated with ozanimod than placebo,” presented D’Haens. Most AEs occurred in the first 3–6 months of ozanimod treatment. “As the time of exposure becomes longer, the [number of] patients who have TEAEs decreases,” he added.
“There was no evidence of new patterns of TEAEs with longer exposure to ozanimod. When adjusting for study duration, no TEAEs indicative of a long-term cumulative toxicity were observed,” the authors said.