Relationship Between Infections and Absolute Lymphocyte Count During Phase 3 and Open-label Extension Trials of Ozanimod in Patients With Relapsing Multiple Sclerosis
Hans-Peter Hartung1, Lawrence Steinman2, Amit Bar-Or3, James K. Sheffield4, Sarah Harris4, Jon V. Riolo4, Chun-Yen Cheng4, Diego Silva4, Bruce A. C. 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, 2Beckman 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:

To describe the absolute lymphocyte counts (ALC) at the time of first infection in patients with relapsing multiple sclerosis (RMS) who received ozanimod 0.92 mg/d in phase 3 parent trials (SUNBEAM‒NCT02294058; RADIANCE‒NCT02047734) and an open-label extension (OLE) trial (DAYBREAK‒NCT02576717).

Background:

Ozanimod is a sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator for treatment of adults with relapsing multiple sclerosis (RMS). S1P receptor modulators decrease ALC by reducing lymphocyte egress from secondary lymphoid organs.

Design/Methods:

Patients in the parent/OLE trials with ALC measured 92 days before or after their first infection were divided into  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). The incidence of total infections, serious infections, and opportunistic infections was assessed by group in the parent trials and the OLE trial.

Results:

During the parent trials, 762 patients had a postbaseline ALC assessment. At the time of first infection, 3.9%, 3.5%, 15.4%, 13.0%, and 0.3% of patients 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 patients had a postbaseline ALC assessment. At the time of first infection, 7.4%, 5.9%, 21.5%, 20.7%, and 1.0% of patients had ALC in groups 1-5, respectively. At first serious infection, 0.1%, 0.3%, 1.1%, 1.2%, and 0.04% had ALC in groups 1-5, and at first opportunistic infection, 0.7%, 0.3%, 1.4%, 2.6%, and 0.1% had ALC in groups 1-5, respectively.

Conclusions:

At the time of first infection, most patients had ALC between 0.2×109/L and 0.8×109/L; few had ALC <0.2×109/L. There was no association between infections and lymphopenia degree in patients receiving ozanimod.

10.1212/WNL.0000000000202336