DX05
Analysis of Lymphocyte Counts and Infection Rates with Fingolimod in Patients with Primary Progressive Multiple Sclerosis over the Informs Trial

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Edward J. Fox, MD, PhD , Central Texas Neurology Consultants, Round Rock, TX
Fred Lublin, MD , Icahn School of Medicine at Mount Sinai, New York, NY
Jerry S Wolinsky, MD , McGovern Medical School, UTHealth, Houston, TX
Jeffrey A Cohen, MD , Cleveland Clinic Foundation, Cleveland, OH
Xiangyi Meng, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Marina Ziehn, PhD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Scott Kolodny, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Norman Putzki, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ
Bruce AC Cree, MD, PhD , UCSF Neurology, Weill Institute for Neurosciences, San Francisco, CA
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Background:

INFORMS was a double-blind, phase 3, randomized trial assessing efficacy and safety of fingolimod versus placebo over 36–60 months in patients with primary progressive multiple sclerosis (MS). Peripheral lymphopenia is an inherent mechanistic effect of fingolimod, and was not associated with increased infection risk in controlled trials in MS.

Objectives:

To assess whether degree of reduced lymphocyte count (LC) is associated with differences in infection rates in patients with MS during controlled fingolimod treatment.

Methods:

In INFORMS, patients were randomized to fingolimod 0.5 mg (N=336; exposure, 908.1 patient-years) or placebo (N=487; exposure, 1423.5 patient-years). LC was measured at each study visit. Rates of infection-related adverse events (AEsinf) per 100 patient-years were assessed post hoc for subgroups of patients stratified by on-study nadir LC (NLC).

Results:

Mean LC reductions remained stable during treatment with fingolimod, as did the percentage of patients with very low LCs (<0.2×109/L) at any study visit (range 2.5–6.8%; fingolimod discontinuation owing to LC decrease, n=1). Rates of AEsinf/100 patient-years were similar with fingolimod (53.6 [95% confidence interval (CI), 46.9–61.0]) and placebo (51.9 [95% CI, 46.5–57.7]). There was no apparent relationship between NLC and rate of AEsinf/100 patient-years with fingolimod (patients with NLC <0.2×109/L [n=59], 63.9; NLC 0.2–0.4×109/L [n=179], 46.3; NLC >0.4×109/L [n=98], 64.5). AEsinf of interest for fingolimod appeared independent of NLC, including the rates/100 patient-years of respiratory tract infections (overall, 16.4 [95% CI, 13.5–19.7]; NLC subgroups, 6.8–24.9) and herpes infections (overall, 2.5 [95% CI, 1.6–3.8]; NLC subgroups, 0.0–4.2); these rates were broadly similar to those with placebo (respiratory tract, 18.1 [95% CI, 15.6–20.9]; herpes, 2.5 [95% CI, 1.7–3.5]).

Conclusions:

These data suggest that, during fingolimod treatment, degree of reduction of peripheral LC was not associated with increased risk of respiratory tract or herpes infections, or with overall infection rates.

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