Ozanimod Could be an Alternative to Anti-TNF Drugs for Crohn's Disease

Brian Feagan, MD

Ozanimod could soon be added to the ever growing stable of potential treatments for Crohn’s disease.

A team, led by Brian G. Feagan, MD, University of Western Ontario, evaluated the effects of ozanimod, an oral agent that selectively targets sphingosine-1-phosphate receptor subtypes 1 and 5, on endoscopic disease activity for patients with Crohn’s disease.

While tumor necrosis factor antagonists have improved Crohn’s disease in recent years, fewer than 50% of patients have achieved sustained benefits. The investigators believe durable maintenance therapy with orally administered could be an alternative treatment.

In the phase 2, uncontrolled, multicenter trial dubbed STEPSTONE, the investigators examined 69 adults with moderately to severely active Crohn’s disease recruited at 28 hospital and community research centers in Canada, the US, Hungary, Poland, and Ukraine.

Each patient began treatment with a 7-day dose escalation that included 4 days on ozanimod 0.25 mg daily and 3 days of ozanimod 0.5 mg daily.

Next, the patients received ozanimod 1.0 mg oral capsules daily for an 11 additional weeks followed by a 100-week extension.

The investigators sought primary endpoints of the change in Simple Endoscopic Score for Crohn’s Disease (SES-CD) from baseline to week 12, which was determined by a blinded central reader.

At week 12, the mean change from baseline in SES-CD was -2.2 (SD, 6.0), while 16 (23.2%; 95% CI, 13.9—34.9) patients achieved an endoscopic response.

The investigators also identified a reduction from baseline in Crohn’s Disease Activity Index (CDAI) scores (mean change −130.4; SD 103.9).

They also found clinical remission (CDAI <150 points) in 27 (39.1%; 95% CI, 27.6—51.6) patients and response (CDAI decrease from baseline ≥100) in 39 (56.5%; 95% CI, 44.0–68.4) participants.

The mean change from baseline in two-item patient-reported outcome (PRO2, stool frequency, abdominal pain scores) score was −66.1 (SD, 65.4). and the mean change from baseline in Geboes Histology Activity Score (GHAS) was -5.9 (SD, 11.0) and in Robart’s Histopathology Index (RHI) was -10.6 (25.1).

The investigators did identify some adverse events, which Crohn’s disease flares found in 18 (26.0%) patients. The most commonly reported serious treatment-related adverse events were Crohn’s disease in 6 patients (9%) and abdominal abscess in 2 individuals (3%).

“Endoscopic, histological, and clinical improvements were seen within 12 weeks of initiating ozanimod therapy in patients with moderately to severely active Crohn's disease. Phase 3 placebo-controlled trials have been initiated,” the authors wrote.

Recently, researchers presented data showing another treatment—upadacitinib&mdash;is effective treating Crohn’s disease.

In the randomized, double-blind, phase 2 trial, the investigators tested 220 adults with moderate to severe Crohn’s disease who had an inadequate response or intolerance to immunosuppressants or tumor necrosis factor antagonists.

Equal amounts of patients received either 3, 6, 12, or 24 mg of the oral selective Janus kinase 1 inhibitor, or a placebo twice daily or 24 mg upadacitinib once daily.

Of the 220 patients, 13% achieved clinical remission receiving 3 mg of the study drug, while 27% of patients receiving 6 mg upadacitinib (P <0.1 vs placebo), 11% of patients receiving 12 mg upadacitinib, and 22% of patients receiving 24 mg upadacitinib twice daily, and by 14% of patients receiving 24 mg upadacitinib once daily, compared to 11% of patients receiving placebo achieved remission.

Endoscopic remission was achieved by 10% (P < .1 vs placebo), 8%, 8% (P < .1 vs placebo), 22% (P < .01 vs placebo), and 14% (P < .05 vs placebo) of patients receiving upadacitinib, respectively, while none of the patients receiving placebo achieved endoscopic remission.

The study, “Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study,” was published online in The Lancet Gastroenterology & Hepatology.