Severe CD4 Lymphocytopenia in Patients with Multiple Sclerosis Treated with Fingolimod
Journal of Allergy and Clinical Immunology
RATIONALE: Fingolimod, a sphingosine 1-phosphate receptor modulator is approved as an oral daily therapy for relapsing - remitting multiple sclerosis (MS). It works by reducing lymphocyte egress from lymphocytes, thereby limiting their autoimmune effects in the CNS. This medication is known to causes a lymphopenia and leukopenia but its immunosuppressive potential is not well appreciated by practicing physicians. METHODS: Two women taking fingolimod for MS were referred to our immunology clinic for evaluation of hypogammaglobulinemia. Additional immune testing was initiated. The published medical literature on the immune effects of fingolimod was reviewed. RESULTS: Patient #1 was age 59 and had four separate bouts of zoster prior to starting therapy with fingolimod. She had a fifth zoster event while on the medication. Patient #2 was age 67. Neither patient had prior therapy with immunosuppressive drugs or natalizumab. The immune studies in both patients revealed lymphopenia, mild leukopenia, mild hypogammaglobulinemia, a severe CD4 lymphocytopenia (/L absolute) and lymphocyte subset phenotypes indistinguishable from that seen in patients with advanced AIDS. Tests for HIV were negative. To date, increase in zoster infections, multiple basal cell skin cancers and 15 cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fingolimod. CONCLUSIONS: Profound immune changes, especially with severe CD4 lymphocytopenia, can occur in patients on fingolimod therapy. There is a need to better define the risks for opportunistic infections and tumors treated with this medication.
Lauter CB, Aneese AM, Rodriguez FF, Eilender L. Severe CD4 Lymphocytopenia in Patients with Multiple Sclerosis Treated with Fingolimod. Journal of Allergy and Clinical Immunology. 2019 Feb 1;143(2):AB111.