DX31
Lymphocyte Count Reductions in Relapsing-Remitting MS Patients Treated with Delayed-Release Dimethyl Fumarate: Integrated Analysis of the Placebo-Controlled Studies

Thursday, May 29, 2014
Trinity Exhibit Hall
J. Theodore Phillips, MD, PhD, FAAN , Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX
Robert J Fox, MD, FAAN , Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH
Ralf Gold, MD , Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany
Krzysztof Selmaj, MD, PhD , Department of Neurology, Medical University of Lodz, Lodz, Poland
Kartik Raghupathi, MS , Biogen Idec, Inc., Cambridge, MA
Huixing Yuan, PhD , Biogen Idec, Inc., Cambridge, MA
John O'Gorman, PhD , Biogen Idec, Inc., Cambridge, MA
Mark Novas, MD , Biogen Idec, Inc., Cambridge, MA
Vissia Viglietta, MD, PhD , Biogen Idec, Inc., Cambridge, MA
Nuwan C Kurukulasuriya, PhD , Biogen Idec, Inc., Cambridge, MA
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Background: Delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and an acceptable safety profile in placebo-controlled clinical trials, including a Phase 2b trial and the Phase 3 DEFINE and CONFIRM studies. The most common adverse events (AEs) with delayed-release DMF were flushing and GI events, but delayed-release DMF was also associated with a reduction in lymphocyte counts.

Objectives: To describe the clinical relevance of lymphocyte count reductions with delayed-release DMF, based on an integrated analysis of the placebo-controlled Phase 2b, DEFINE, and CONFIRM studies.

Methods: The analysis comprised 2,428 RRMS patients who received placebo (n=836) or delayed-release DMF 240mg twice (BID; n=769) or three times daily (TID; n=823) for up to 96 weeks. CONFIRM included a glatiramer acetate reference comparator arm (n=351; results not shown).

Results: In delayed-release DMF-treated patients, mean white blood cell and lymphocyte counts decreased by approximately 11% and 30%, respectively, through Week 48, then plateaued, but remained within normal limits throughout the observation period. Percentages of patients with worst post-baseline Common Terminology Criteria (CTC) Grades 1, 2, or 3, respectively, were higher in the BID (10%, 22%, 6%) and TID (8%, 18%, 3%) groups than in the placebo group (2%, 2%, <1%). Percentages of patients with >1 Grade 3 or 4 lymphocyte count were 0% (placebo), 3% (BID), and 1% (TID), and with consecutive Grade 3 or 4 lymphocyte counts were 0% (placebo), 2% (BID), and 1% (TID). The incidence of Grade 3 or 4 lymphopenia increased through Week 48, then stabilized. There was no clear pattern of increased incidence of infections or serious infections with increasing post-baseline lymphocyte CTC grade. No patients discontinued study drug due to lymphopenia. Four weeks after stopping delayed-release DMF, mean lymphocyte counts increased but did not return to baseline.

Conclusions: Treatment with delayed-release DMF was associated with decreased lymphocyte counts but no overall increased risk of infection.

See more of: Disease Management, Mechanisms, and Treatment (Poster)
See more of: CMSC
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