Absolute Lymphocyte Count Around Infections During Phase 3 and Open-label Extension Trials of Ozanimod in Participants with Relapsing Multiple Sclerosis
Hans-Peter Hartung1, Lawrence Steinman2, Amit Bar-Or3, James Sheffield4, Sarah Harris4, Jon Riolo4, Chun-Yen Cheng4, Jennifer Reardon4, Andrew Thorpe4, Bruce Cree5
1Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf Germany; Brain and Mind Centre, University of Sydney, Australia; Department of Neurology, Medical University of Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 2Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, 3Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 4Bristol Myers Squibb, Princeton, New Jersey, 5Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California
Objective:
Describe absolute lymphocyte count (ALC) at the time of a first infection in participants with relapsing multiple sclerosis treated with ozanimod 0.92 mg/d in phase 3 “parent” trials (SUNBEAM‒NCT02294058; RADIANCE‒NCT02047734) and an open-label extension (OLE) trial (DAYBREAK‒NCT02576717).
Background:
Sphingosine 1-phosphate receptor modulators decrease peripheral blood ALC by reducing lymphocyte egress from secondary lymphoid organs.
Design/Methods:
Participants in the parent and OLE trials (data cutoff: 02/01/2022) with ALC measured 92 days before or after their first infection were included and were divided into 5 ALC groups: ≥lower limit of normal (LLN) (group 1), 0.8×109/L‒<LLN (group 2), 0.5‒<0.8×109/L (group 3), 0.2‒<0.5×109/L (group 4), and <0.2×109/L (group 5). Incidences of total infections, serious infections, and opportunistic infections were assessed by ALC group in the parent trials (ozanimod 0.92 mg group) and the OLE (all subjects received ozanimod 0.92 mg).
Results:

During the parent trials, 762 ozanimod-treated participants had a postbaseline ALC assessment. At the time of any first infection, 3.9%, 3.5%, 15.4%, 13.0%, and 0.3% of the 762 participants had ALC in groups 1-5, respectively. At the time of first serious infection, 0.1%, 0.1%, 0.4%, 0.3%, and 0% had ALC in groups 1-5, and at first opportunistic infection, 0.4%, 0.1%, 0.7%, 0.5%, and 0% had ALC in groups 1-5, respectively.

During the OLE trial, 2251 participants had a postbaseline ALC assessment. At the time of any first infection, 8.4%, 6.6%, 23.3%, 21.9%, and 1.1% of the 2251 participants had ALC in groups 1-5, respectively. At first serious infection, 0.2%, 0.6%, 1.4%, 1.4%, and <0.1% had ALC in groups 1-5, and at first opportunistic infection, 0.7%, 0.4%, 1.5%, 2.9%, and 0.1% had ALC in groups 1-5, respectively.

Conclusions:
Most participants had ALC between 0.2×109/L and 0.8×109/L at the time of any first infection, opportunistic infection, or serious infection; few had ALC <0.2×109/L.
10.1212/WNL.0000000000204936