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(DIR) Return to: GILENYA (fingolimod, FTY720)
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#Post#: 1110--------------------------------------------------
Rebound syndrome in MS patients after stopping Gilenya
By: agate Date: February 17, 2016, 2:44 pm
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Being presented at the annual ACTRIMS (Americas Committee for
Treatment and Research in Multiple Sclerosis) conference in New
Orleans, February 18-20, 2016.
[quote]Rebound syndrome in multiple sclerosis patients after
cessation of fingolimod
Ms. Stacy E Hatcher, BS1, Dr. Emmanuelle Waubant, MD, PhD2, Dr.
Bardia Nourbakhsh, MD1, Dr. Elizabeth Crabtree-Hartmann, MD1 and
Dr. Jennifer S Graves, MD, PhD, MAS2
1UCSF, San Francisco, CA, 2University of California, San
Francisco, San Francisco, CA
Background:
Rebound syndrome after natalizumab cessation has been
well-documented. However, rebound activity after discontinuation
offingolimod, a sphingosine-1-phosphate receptor modulator used
to treat relapsing remitting multiple sclerosis is less well
understood.
Objectives:
To describe multiple sclerosis (MS) rebound syndrome after
fingolimod cessation.
Methods:
We identified patients at the UCSF MS Center who experienced
severe relapse with multiple new enhancing lesions upon
cessation of fingolimod. Clinical and demographic data were
extracted from electronic medical records and magnetic resonance
images (MRI) were reviewed by UCSF MS neurologists. We conducted
a literature search and identified additional cases of severe
relapse upon fingolimod cessation.
Results:
Five women (ages 29-45) with a history of relapsing-remitting MS
experienced severe relapse at 4-16 weeks post fingolimod
cessation. Reasons for stopping therapy included pregnancy
attempts (n=2), clinical progression on fingolimod (n=2), and
medication side effects (n=1).
Despite varying prior disease course, all experienced
unexpectedly severe clinical relapses accompanied by drastic
increases in MRI lesion burdens. In three patients new lesion
development persisted for 3-6 months despite treatment with
corticosteroids and in two patients, initiation of B cell
depleting therapy. Eleven patients identified through literature
review were reported as having severe relapses consistent with a
rebound syndrome.
Conclusion:
These cases provide evidence for a rebound syndrome following
cessation of fingolimod. They highlight the need to determine
the best methods for sequencing or discontinuing MS therapies.
Further study is also needed to prevent rebound in women
[stopping] therapies for pregnancy. These issues will become
increasingly important as newer agents with strong immunological
effects are introduced on the market.
Inclusion in phase II clinical trials of at least a 2-3 month
observation phase for patients who discontinue study drug may
provide valuable information to clinicians prescribing [these
drugs and monitoring their patients in the transition to and
from them].[/quote]
#Post#: 1203--------------------------------------------------
(JAMA Neuro.) Article on rebound syndrome by same authors
By: agate Date: May 2, 2016, 8:08 pm
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An article by the same authors on the same topic appears inJAMA
Neurology, May 2, 2016, and is available in its entirety online.
This is the abstract:
[quote]Rebound Syndrome in Patients With Multiple Sclerosis
After Cessation of Fingolimod Treatment
Stacy Ellen Hatcher, BS1; Emmanuelle Waubant, MD, PhD1; Bardia
Nourbakhsh, MD1; Elizabeth Crabtree-Hartman, MD1; Jennifer S.
Graves, MD, PhD, MAS1
Author Affiliations
1Department of Neurology, University of California, San
Francisco
Importance
The appropriate sequencing of agents with strong immune system
effects has become increasingly important. Transitions require
careful balance between safety and protection against relapse.
The cases presented herein highlight that rebound events after
ceasing fingolimod treatment may happen even with short washout
periods (4 weeks) and may perpetuate despite steroid treatment
or the immediate use of fast-acting immune therapies, such as
rituximab.
Objective
To describe rebound syndrome in patients with multiple sclerosis
(MS) after cessation of fingolimod treatment.
Design, Setting, and Participants
Clinical and demographic data were extracted from electronic
medical records from the University of California, San
Francisco, Multiple Sclerosis Center from January 2014 to
December 2015. Magnetic resonance images were reviewed by MS
neurologists (J.S.G., E.W., B.N., and E.C.H.).
Rebound syndrome was defined as new severe neurological symptoms
after ceasing fingolimod treatment, with the development of
multiple new or enhancing lesions exceeding baseline activity.
We reviewed the PubMed database from January 2010 to December
2015 for similar cases of severe disease reactivation after
ceasing fingolimod treatment using search terms fingolimod and
either rebound or reactivation.
Participants were included if they stopped receiving fingolimod
between January 2014 and December 2015. Five patients were
identified who experienced rebound after ceasing fingolimod
treatment.
Exposures
Each patient received treatment with oral fingolimod for
various durations.
Main Outcomes and Measures
Occurrence of rebound after ceasing fingolimod treatment.
Results
The mean (SD) age of the 5 female patients presented in this
case series was 35.2 (6.4) years. Of the 46 patients who stopped
fingolimod treatment within the 2-year period, 5 (10.9%)
experienced severe relapse 4 to 16 weeks after ceasing
fingolimod treatment.
Despite varying prior severity of relapsing-remitting course,
all participants experienced unexpectedly severe clinical
relapses accompanied by drastic increases in new or enhancing
lesions seen on magnetic resonance imaging evidenced by a median
(range) increase of 9 (0->30) new gadolinium-enhancing lesions
and a median (range) of 9 (0->30) new T2 lesions. New lesion
development persisted for 3 to 6 months despite treatment with
corticosteroids (n = 3) and initiation of B-cell
depleting therapy (n = 2).
In addition, 11 patients were identified through literature
review reported as having severe relapses consistent with a
rebound syndrome and similar features to our 5 cases.
Conclusions and Relevance
These cases provide evidence for a fingolimod rebound syndrome
at a clinically relevant frequency, highlighting the need to
determine the best methods for sequencing or discontinuing MS
therapies. A large prospective registry or population-based
study would be helpful to confirm this rebound phenomenon and to
determine contributing factors, including immune biomarkers,
that increase risk for this syndrome.[/quote]
The entire article can be seen here
(HTM) http://archneur.jamanetwork.com/article.aspx?articleID=2516773.
#Post#: 1209--------------------------------------------------
Rebound syndrome in MS patients after stopping Gilenya (JAMA Ed
itorial)
By: agate Date: May 7, 2016, 8:59 pm
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The same issue (May 2) of JAMA Neurology contains an editorial
about the article above. It points out that both Tysabri and
Gilenya have involved rebound effects when patients stopped
taking the drug, while the older disease-modifying drugs have
not involved a rebound effect.
The editorial goes on to summarize a couple of instances of
combinations of drugs--indicating that estriol combined with
Copaxone showed good results in a Phase 2 trial in terms of the
relapse rate.
(HTM) http://app.jamanetwork.com/#page=issuesContainer
(HTM) http://app.jamanetwork.com/#page=issuesContainer
NOTE: Using the above link, you need to click on "Continue
without promo code" to see the text of the editorial.
#Post#: 1384--------------------------------------------------
Re: Comments and authors' reply on fingolimod rebound syndrome a
rticle
By: agate Date: September 26, 2016, 1:18 pm
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A couple of letters and an authors' reply about this article, in
JAMA Neurology, September 26. The first is from some Novartis
employees, and the second is from an MD in psychopharmacology,
and they are followed by the authors' reply.
(HTM) http://amaprod.silverchaircdn.com/data/Journals/NEUR/0/nle160035.pdf.gif
(HTM) http://amaprod.silverchaircdn.com/data/Journals/NEUR/0/nle160037.pdf.gif
(HTM) http://amaprod.silverchaircdn.com/data/Journals/NEUR/0/nlr160022.pdf.gif
#Post#: 1677--------------------------------------------------
(AAN abst.) Rebound of MS disease activity after fingolimod cess
ation
By: agate Date: May 11, 2017, 6:38 pm
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Presented at the AAN annual meeting in Boston (April 2017):
[quote]Rebound of Multiple Sclerosis Disease Activity Following
Fingolimod Cessation
Afagh Garjani1, Esmaeil Nikfekr1, Jithin George1
1
Neurology Department, University Hospitals Leicester NHS Trust
Objective:
To describe the rebound of multiple sclerosis (MS) disease
activity after cessation of fingolimod treatment.
Background:
Fingolimod is a sphingosine 1-phosphate receptor modulator which
prevents lymphocyte release from lymphoid tissue. While rebound
of disease activity in MS after discontinuation of natalizumab
is well-known, evidence of rebound after stopping fingolimod has
emerged recently. Further studies on the impact of fingolimod
cessation on relapses would have implications in planning the
transition between disease modifying treatments.
Design/Methods:
We retrospectively reviewed medical records of patients with MS
from the University Hospitals of Leicester, United Kingdom who
had fingolimod discontinued since 2013.
In this case series, we present the clinical, laboratory, and
imaging findings of five patients [who] experienced severe
recurrence of MS relapses after fingolimod withdrawal which
exceeded their baseline disease activity.
We reviewed the literature from PubMed database using the search
term ‘fingolimod rebound’.
Results:
Five (31.2%) of the 16 patients with relapsing-remitting MS
[who] stopped receiving fingolimod suffered from an
unexceptionally severe clinical relapse 2 weeks to 6 months
after fingolimod cessation.
The mean (SD) duration of fingolimod treatment in these female
patients was 21.8 (13.9) months. In all five cases, fingolimod
was discontinued for escalation to natalizumab as a result of
highly active MS. All patients demonstrated substantial
new and enhancing lesions on magnetic resonance imaging (MRI).
Three patients had tumefactive demyelinating lesions.
All patients received corticosteroids. One patient with
encephalopathy and positive John Cunningham virus antibody
required further treatment with cyclophosphamide.
Conclusions:
These cases along with similar reports in the literature
highlight the need to establish a scheme for switching from
fingolimod to other therapies. Further investigations that
incorporate patients who have discontinued fingolimod
for reasons other than highly active MS, such as adverse effects
of fingolimod or progression to secondary progressive MS, can
help to identify predictors of MS rebound after fingolimod
discontinuation. [/quote]
#Post#: 2288--------------------------------------------------
FDA warns of rare risk of severe worsening in MS disability afte
r stopping Gilenya
By: agate Date: November 27, 2018, 8:40 pm
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From Multiple Sclerosis News Today (November 27, 2018), "FDA
Warns about Rare Risk of Severe Worsening of MS Disability after
Stopping Gilenya":
(HTM) https://multiplesclerosisnewstoday.com/2018/11/26/fda-warns-about-risk-of-severe-worsening-of-ms-disability-after-stopping-gilenya/
#Post#: 3625--------------------------------------------------
(Abst.) Risk of fingolimod rebound after switch to cladribine or
rituximab
By: agate Date: April 25, 2022, 11:00 am
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From PubMed (April 25, 2022)--"Risk of fingolimod rebound after
switching to cladribine or rituximab in multiple sclerosis":
(HTM) https://pubmed.ncbi.nlm.nih.gov/35462167/
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