Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

BMC Neurology, Aug 2014

Background Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of fingolimod on MRI outcomes compared to natalizumab treatment has not been investigated in (head to head) clinical trials. Clinical experience with natalizumab is much more extended and in general practice often preferred. Case presentation This case describes a 31-year old woman with RRMS, who experienced severe side effects on natalizumab. After a voluntary four months treatment free period, a severe relapse appeared which was treated with prednisone and plasmapheresis; thereafter fingolimod was initiated. In the following months MRI signs improved spectacularly. Conclusion This case suggests that fingolimod might be a good alternative for natalizumab, especially for use in RRMS patients, with highly active, advanced disease, when natalizumab treatment is stopped due to side effects or even after a severe relapse.

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Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

Anne-Hilde Muris 0 1 Linda Rolf 0 1 Jan Damoiseaux Ellen Koeman Raymond Hupperts 0 1 0 Academic MS Center Limburg, Orbis Medical Center , Sittard , the Netherlands 1 School for Mental Health and Neuroscience, Maastricht University Medical Center , Universiteitssingel 40, Maastricht, theNetherlands Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFN) or placebo. The effect of fingolimod on MRI outcomes compared to natalizumab treatment has not been investigated in (head to head) clinical trials. Clinical experience with natalizumab is much more extended and in general practice often preferred. Case presentation: This case describes a 31-year old woman with RRMS, who experienced severe side effects on natalizumab. After a voluntary four months treatment free period, a severe relapse appeared which was treated with prednisone and plasmapheresis; thereafter fingolimod was initiated. In the following months MRI signs improved spectacularly. Conclusion: This case suggests that fingolimod might be a good alternative for natalizumab, especially for use in RRMS patients, with highly active, advanced disease, when natalizumab treatment is stopped due to side effects or even after a severe relapse. - Background Fingolimod (FTY720, Gilenya, Novartis Pharma AG, Basel, Switzerland) is like natalizumab (Tysabri, Biogen Idec Inc, Weston, MA, USA) a single disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS) patients. Fingolimod is registered in 80 countries across the world. In some countries, like the USA, Switzerland, Australia and Russia, fingolimod is approved as a first line treatment while in Europe and Canada fingolimod is a second line therapy especially for those patients who are non-respondent to at least one other DMT like interferon beta (IFN) or glatiramer acetate (GA) or who have rapidly evolving MS [1-3]. Fingolimod is an oral sphingosine 1-phosphate receptor modulator and acts as a functional antagonist reducing the amount of circulating pathogenic lymphocytes by inhibiting mainly nave T cells and central memory T cells to egress from the lymph nodes. It might also play a role in the neuroprotection of the central nervous system (CNS) [4]. Phase II and phase III studies with fingolimod have shown a decrease in annual relapse rate, as well as a reasonable decline in gadolinium (Gd) enhancing lesions on MRI, both in number and volume, after up to 36 months of fingolimod treatment compared to either first line treatment with IFN or placebo [5-7]. The effect of fingolimod compared to natalizumab treatment has never been investigated in a head-to-head clinical trial. However, natalizumab was approved approximately five years before fingolimod and therefore the clinical experience with natalizumab is much more extended and in general practice often preferred [1,2,8]. When natalizumab is discontinued, because of various reasons, a switch to fingolimod is an obvious next step. However, reactivation of disease in patients switching from natalizumab to fingolimod is reported in a considerable proportion of patients [9-11]. Here we describe a case of a patient who suffered from highly active RRMS which was treated with fingolimod following a severe relapse after discontinuation of natalizumab and a treatment free interval of four months. We consider this case as a striking example of the positive effect that fingolimod treatment may have especially on MRI outcome, even after successful natalizumab treatment. Case presentation A 31-year old woman was diagnosed with RRMS at the age of 25. Three years before diagnosis she presented with a first event of one-sided optic neuritis. She did not have any further medical history. Several first line treatments, i.e. GA and IFN-1b had insufficient effect: exacerbation rate remained high and MRI showed a slight increase in lesion number (Figure 1A). While second line therapy was not indicated because of patients desire to become pregnant, treatment with intravenous immunoglobulins was initiated. Immunoglobulins are not a registered therapy in MS, but can be used off-label if no other options are available [12]. However, relapse rate remained high and one and a half year after IFN-1b was stopped, she was still in a moderate clinical condition and MRI showed multiple new T1 Gd enhancing lesions. Therefore, after a third relapse during immunoglobulin treatment, treatment with natalizumab was initiated. The one relapse she experienced during the natalizumab treatment was in an early phase, and therefore might have been still the result of the highly active MS before the effects of natalizumab. MRI, 11 months after initiation of natalizumab, showed a slight increase in white matter lesions on T2 (FLAIR) MRI without any T (...truncated)


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Anne-Hilde Muris, Linda Rolf, Jan Damoiseaux, Ellen Koeman, Raymond Hupperts. Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions, BMC Neurology, 2014, pp. 164, 14, DOI: 10.1186/s12883-014-0164-5