Lymphocyte Dynamics During and After Fingolimod Therapy: Long-Term Data from the INFORMS Trial (P5.294)

OBJECTIVE: To evaluate the long-term effect of fingolimod on peripheral lymphocyte counts in patients with multiple sclerosis (MS). BACKGROUND: A reduction in peripheral blood lymphocytes is an expected pharmacodynamic outcome of fingolimod therapy. The INFORMS study, conducted in patients with primary progressive MS (PPMS), is the longest controlled trial of fingolimod (≥3 years) to date and provides an opportunity to evaluate the long-term effects of fingolimod on lymphocyte count dynamics. METHODS: INFORMS was an international, double-blind trial that randomized patients to fingolimod 0.5 mg (n=336) or placebo (n=487). Inclusion criteria included: a PPMS clinical diagnosis; disease duration 2-10 years; and objective evidence of disability progression within 2 years. Lymphocyte counts were measured at each study visit. Study drug was interrupted for patients with confirmed on-study lymphocyte counts 9 /L. RESULTS: Within 1 month of fingolimod 0.5mg initiation, mean (SD) lymphocyte counts were reduced to 29[percnt] of baseline values (baseline: 1.79X10 9 /L [0.54]; Month 1: 0.52X10 9 /L [0.28]; n=318). Mean counts remained stable with fingolimod 0.5 mg at 26-29[percnt] of baseline values for all time-points up to 4 years (Month 48: 0.49X10 9 /L [0.28]; n=59). Following fingolimod discontinuation, mean lymphocyte counts returned to 76[percnt] of baseline values at 3 months (1.39X10 9 /L [0.62]; n=74) and 86[percnt] at 6 months (1.70X10 9 /L [0.59]; n=35). Placebo-treated patients experienced no marked change in mean lymphocyte counts with values of 96-102[percnt] of baseline levels up to 4 years. The incidence of infection and infestation was comparable between the fingolimod 0.5mg and placebo groups, in line with previous studies in relapsing MS. CONCLUSIONS: Fingolimod induced a rapid reduction in lymphocyte counts that subsequently remained stable and did not increase the overall incidence of infections and infestations relative to placebo for up to 5 years treatment. Lymphocyte counts returned towards normal within 3-6 months of fingolimod discontinuation.Study Supported by Novartis Pharma AG Disclosure: Dr. Lublin has received personal compensation for activities with Acorda Therapeutics, Inc., Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience, Inc.,Genzyme, Sanofi, Celgene, Cognition Pharmaceuticals, Inc., Elsevier, NIH, and NMSS. Dr. Freedman has received research support from Bayer Healthcare and Genzyme. Dr. Cree has received personal compensation for activities with Abbvie, Biogen Idec, EMD Serono, Genzyme/sanofi aventis, Medimmune, Novartis and Teva. Dr. Cree has received research support from Acorda, EMD Serono, Hoffman La Roche, MedImmune, Novartis a Dr. Wolinsky has received royalty payments from Chemicon International through the University of Texas Health Science Center at Houston. Dr. Weiner has nothing to disclose. Dr. Lubetzki has received personal compensation for activities with BiogenIdec, Novartis, Genzyme, and Roche. Dr. Hartung has received personal compensation for activities with from Bayer, Biogen, GeNeuro, Genzyme as speaker, committee member, consultant. Dr. Montalban has received personal compensation for activities with Actelion, Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck u0026 Co., Inc., NeuroTex, Novartis, Octopharma, Receptos, and Roche Diagnostics Corporation as a speaker. Dr. Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Pharmaceuticals, Genzyme, and Roche. Dr. Merschhemke has received personal compensation for activities with Novartis as an employee. Dr. Li has received personal compensation for activities with Novartis Pharmaceuticals as an employee. Dr. Putzki has received personal compensation for activities with Novartis Pharma AG. Dr. Haering has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH.