Author's Reply

Sir,

We thank the respondents for expressing an interest in the article. Our comments are as follows:

Fingolimod (FTY 720) is a modulator of the sphingosine 1-phosphate receptor (S1P-R) on the surface of the lymphocytes and inhibits their ability to travel from the lymph nodes to the peripheral circulation and thereby ensuring the decreased entry of potentially encephalitogenic T cells to the CNS in multiple sclerosis.[1] The substantial decrease in blood lymphocyte counts that occurs in a Fingolimod-treated patient reflects their sequestration in the lymph nodes rather than a destruction of lymphocytes. Thus Fingolimod-treated patients may have preservation of many aspects of the immune system, including the capacity for lymphocyte activation in lymph nodes and tissues, the capacity to generate antibodies, and other innate immune responses.[2] This retaining of the functional capacity of the lymphocytes is very important and explains why Fingolimod-treated patients do not develop the frank clinical features of immune suppression.

The reference cited by the respondents mentioning that 2000 patients were taken as part of the FREEDOMS trial is a website of a commercial firm which deals in outsourcing of the drug development technology. However, we draw your attention to the original FREEDOMS trial published in NEJM which clearly mentions that 1272 patients were studied as part of this placebo-controlled trial.[3]

The TRANSFORMS trial witnessed two deaths; one patient died because of primary Varicella zoster infection and the other succumbed to herpes simplex encephalitis. Both the fatalities were seen in patients receiving 1.25 mg/day of Fingolimod.[4] It is too premature to directly implicate Fingolimod to these deaths at present. However, Fingolimod therapy has shown an association with an increased risk of certain viral infections particularly herpes infections[4] and further studies are likely to throw more light on this adverse event.