Johnson et al. Reconstitution of circulating lymphocyte counts in FTY720-treated MS patients. Clin Immunol. 2010 Oct;137(1):15-20.
Background: FTY720 (Fingolimod) reduces multiple sclerosis disease activity by inducing lymphopenia and inhibiting lymphocyte re-entry from lymph nodes. Peripheral lymphocyte reconstitution following drug discontinuation has been considered relatively rapid (2-4 weeks), based on short-term studies.
Objective: We investigated the kinetics of lymphocyte reconstitution in MSers in open label extension phases of FTY720 clinical trials who discontinued therapy after prolonged use (>1-5 years), and examined histological features of a mediastinal lymph node obtained from a lymphopenic FTY720 MSer.
Results: Although three MSers showed reconstitution of peripheral lymphocytes within the predicted timeline, two MSers continued to be lymphopenic 9 and 34 months after therapy cessation. Lymph nodes from the latter MSer showed preserved architecture.
Conclusion: Notwithstanding preserved lymph node integrity, time for lymphocyte reconstitution after prolonged FTY720 therapy can be significantly greater than predicted by shorter-term studies. This is relevant for clinical decisions regarding management of MSer using this therapy and for introducing alternate therapies.
Rebound post fingolimod:
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Rebound MS disease activity post-fingolimod. From: Neurology. 2012 Nov 6;79(19):2006-7. |
Hakiki et al.Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases. Mult Scler. 2012 Nov;18(11):1636-9.
Objective: To report our experience on fingolimod suspension in MSers. Methods: We evaluated clinical and magnetic resonance (MR) outcomes in 6 MSers after fingolimod discontinuation. Results: Within 3 months from fingolimod suspension, 5 subjects returned to pre-treatment disease activity; one MSers, however, exhibited a clear rebound of clinical and MR activity. Conclusion: Our findings suggest that clinical and MR outcomes after fingolimod suspension can vary among MSers. Systematic collection of clinical, laboratory and imaging data is highly advisable to identify subjects who are at higher risk of rebound and to define effective management strategies in these subjects.