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.
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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)