Risk factors for fingolimod-induced lymphopenia in multiple sclerosis

Background Lymphopenia is a well-known adverse event of fingolimod, a disease-modifying drug for multiple sclerosis (MS). Objectives The objective of this paper is to investigate risk factors for predicting fingolimod-induced lymphopenia in MS by frequent hematological monitoring. Methods We retrospectively reviewed data of fingolimod-treated MS patients. Data assessed were sex, age, disease duration, medication history, body mass index, all attacks, Kurtzke's Expanded Disability Status Scale score, and absolute lymphocyte count (ALC) within two days before initiating fingolimod (baseline), on the day after first administration (day 2), and at least every other month after initiating fingolimod therapy. Results Of 41 MS patients, marked lymphopenia (ALC <200/µl) was confirmed in 12 patients (lymphopenia group) within one year. A significantly more frequent history of treatment with any interferon-beta and lower median baseline ALC was observed in the lymphopenia group than in the non-lymphopenia group (n = 29) (91.7% vs. 44.8%; p = 0.006 and 1469/µl vs. 1879/µl; p = 0.005). An ALC of ≤952/μl on day 2 was the most responsible risk factor for predicting marked lymphopenia (sensitivity, 92%; specificity, 76%; area under the curve, 0.823; p < 0.001). Conclusions Low baseline ALC and treatment history with any interferon-beta were risk factors for fingolimod-induced lymphopenia, possibly predicted from ALC on day 2.