Lymphopenia in Multiple Sclerosis Patients Treated with Delayed-Release Dimethyl Fumarate: Analysis of 2 Electronic Health Record Databases in the US

Background: In clinical trials, delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) significantly reduced clinical and neuroradiological disease activity and exhibited a favorable benefit–risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). DMF treatment was also associated with severe (Grade 3) lymphopenia (absolute lymphocyte counts [ALC] <500 cells/µL) in 6% of patients. More robust data on a large cross-center cohort is needed to understand the effects of DMF on ALCs in the real-world setting.

Objectives: Evaluate ALCs in patients with MS treated with DMF using data from two US electronic health record (EHR) databases.

Methods: Using 2 US EHR databases (Geisinger Health System and Humedica), we identified patients with a diagnosis of MS (ICD-9: 340). Patients included in the analyses received ≥1 prescriptions for DMF and had ALC values available at baseline (within 6 months prior to DMF initiation) and at one or more times during DMF treatment. ALC ≥1000 cells/µL was considered normal.

Results: A total of 1014 patients (201 Geisinger and 813 Humedica) met the inclusion criteria; demographic characteristics of patients were similar (71% and 77% female, respectively; mean age: 44 and 47 years, respectively). Among patients who had both baseline and 12-month ALC values, mean ALCs decreased from 1881 to 1272 cells/µL (32% decrease) in Geisinger and from 1858 to 1339 cells/µL (28% decrease) in Humedica. Among patients who had a normal ALC at baseline, 6% (Geisinger) and 5% (Humedica) developed severe lymphopenia (≥1 ALC <500 cells/µL) during DMF treatment. Mean time from DMF initiation to severe lymphopenia was approximately 9 months.

Conclusions: ALC profiles in DMF-treated patients were generally stable throughout time in the real-world setting. Findings in terms of percentage reduction in ALCs at 12 months, proportion of patients who developed severe lymphopenia, and time to severe lymphopenia were similar to observations in clinical trials. Results indicate that the overall benefit–risk profile remains favorable. Additional analyses are being conducted to examine ALC recovery in severely lymphopenic patients.

Study Supported by: Biogen, Inc.