In contrast to US Food and Drug Administration licensure,4 in Europe fingolimod is approved as a second-line treatment, when other disease-modifying-drugs (DMDs) fail or in very active disease de novo.3 Clearly, in the first setting a live VZV vaccine cannot be administered. With respect to possible DMD treatment, we propose checking for VZV immunoglobulin G antibodies in MS patients selleck without a clear history of chickenpox or a documented completion of the VZV immunization schedule at an early stage, before any MS-specific treatment is necessary, rather than waiting until fingolimod therapy is needed. The attenuated varicella vaccine is safe and does not seem to accelerate MS disease progression.7 The success of any vaccination during immunomodulating or immunosuppressive treatment should be determined by sufficient antibody titer increase following vaccination as a matter of principle. FTY720 (fingolimod) is a novel immunomodulator and representative of sphingosine 1-phosphate receptor FTY720 (fingolimod) is a novel immunomodulator and representative of sphingosine 1-phosphate receptor common AE with MMF treatment. Discontinuations due to AEs were higher in the FTY720 versus the MMF arm (22.9 versus 3.7%).
Sixteen patients (32.7%) in the FTY720 arm and nine (16.7%) patients in the MMF arm reported ophthalmic AEs. Macular edema was reported in six patients in AEB071 the FTY720 arm (12.2%) and five in the MMF arm (9.3%). However, patients with risk factors (diabetes, diabetic retinopathy, retinal vascular disease, past ocular surgery and uveitis) for macular edema were higher in the FTY720 versus the MMF arm (57.
1 versus 50.0%). Follow-up evaluations were not available in any of these cases. Three (6.1%) patients on FTY720 and none on MMF had blurring of vision. With both treatments, a transient decrease in heart rate was reported as an AE (FTY720: n ? 8, 16.3%; MMF: n ? 1, 1.9%) and events were not clinically manifested as SAEs. Systolic and diastolic blood pressure was not affected. Decrease in lymphocytes on Day 1 with both treatments recovered on Day 7 in theMMF treatment arm but remained <30% of the baseline value in the FTY720 arm? as would be expected from its known mechanism of action [6]. No serious or severe pulmonary/respiratory events were reported. Mean creatinine clearance (Cockcroft?Gault) at end-of-treatment [FTY720: 273.5 (27?439) days, n ? 46; MMF: 322 (67?469) days, n ? 52] was 62 mL/min in the FTY720 arm and 64 mL/min in the MMF arm. Renal/graft function (serum creatinine and creatinine clearance) was preserved in the patients who were treated for BPAR while continuing study drug (Supplementary table 1). One patient in each treatment arm had malignancy as AE?prostatic carcinoma (MMF) and T-cell lymphoma (FTY720).