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DIR Return to: TECFIDERA (dimethyl fumarate, BG-12, Fumaderm)
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#Post#: 1003--------------------------------------------------
4th PML case for Tecfidera
By: agate Date: November 13, 2015, 6:19 pm
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From MedPage Today, November 13, 2015:
[quote]Will 4th PML Case Change Tecfidera Risk Profile?
Most recent case occurred in patient with only moderate
lymphopenia
by Kristina Fiore
Staff Writer, MedPage Today
Biogen has reported a fourth case of PML with Tecfidera -- this
one in a patient with only moderate lymphopenia -- to U.S. and
European regulators, raising new questions about the drug's
safety.
The latest case occurred in a 61-year-old female with
relapsing-remitting multiple sclerosis, who'd been taking
Tecfidera for 22 months before being diagnosed with PML.
She had grade 2 lymphopenia, at 600 cells/mm3, for 6 months
before developing symptoms of PML, which included left arm
weakness and apraxia, according to information provided to
MedPage Today. Severe grade 3 lymphopenia occurs when lymphocyte
levels drop below 500 cells/mm3.
"To my understanding, at least one of the cases did not
demonstrate grade 3 lymphopenia but only grade 2," said Ari
Green, MD, of the University of California San Francisco. "This
complicates using lymphocyte counts as a means to track risk of
PML, as a not insignificant portion of patients on Tecfidera
develop grade 2 lymphopenia." (Those estimates range from 11% to
21%.)
Few other details about the case were made available. Neither
Biogen nor the FDA or the European Medicines Agency (EMA) would
comment further on the case.
This is not the first case of a patient with moderate
lymphopenia developing PML while taking a dimethyl fumarate
product. Last April, researchers reported in the New England
Journal of Medicine the case of a 64-year-old female patient who
died from PML after 2 years on a compounded formulation of
dimethyl fumarate for psoriasis (Psorinovo). Her lowest
lymphocyte count was 792 cells/mm3.
Another patient taking Biogen's Fumaderm dimethyl fumarate brand
for psoriasis developed PML with only moderate grade 2
lymphopenia at a range of 724 to 738 cells/mm3. The case was
reported in Neurology.
Although questions remain about the best way to use lymphopenia
to determine PML risk with Tecfidera, some experts have raised
concerns about the interval of lymphocyte screening on the
drug's label.
Tecfidera's label calls for a baseline lymphocyte count,
followed by another check-in after 6 months and then regular
checks every 6 to 12 months thereafter. Physicians should
consider stopping therapy in those whose levels stay below 500
cells/mm3 for 6 months.
However, European regulators recently recommended checking
lymphocyte counts every 3 months, and reconsidering treatment in
patients who maintain grade 3 lymphopenia for longer than 6
months.
The EMA also recommends checking lymphocyte count monthly for
those on Fumaderm, and stopping therapy in all patients who
develop grade 3 severe lymphopenia.
Tecfidera's label also only mentions one case of PML, which is
outdated given the total of four cases now reported.
Nor does the label discuss the potential role of JCV antibody
testing to determine PML risk -- despite the fact that many
clinicians are already performing such screening on MS patients.
They use it, however, mostly to determine whether patients
should go on natalizumab (Tysabri), which carries a stronger
risk of PML than most other MS drugs.
Tecfidera is currently seen as a safer choice if a patient is
indeed JCV antibody positive.
"The risk [of PML] does not appear to be high enough to warrant
routine assessment of JCV antibody status in all patients on
Tecfidera," Green said. "Many antimetabolites have a low risk of
PML and I would consider both Gilenya and Tecfidera in that risk
class for now."
Most of the specialists contacted by MedPage Today said they're
not so concerned with FDA label changes, but they would like
drugmaker Biogen to be more forthcoming about the details of the
PML cases.
"I think the current FDA warning letter is sufficient --
although without a risk mitigation and registration program from
the FDA we can't be sure that there aren't more cases for
Tecfidera than what has been reported," Green said.
...
Tecfidera has been available on the U.S. market as a treatment
for MS since 2013.
A Biogen spokesperson confirmed that there have been 588 cases
of PML with natalizumab since 2004, representing a global
incidence of four per 1,000 treated patients.
The company pulled the drug from the market shortly after it was
approved in 2004 -- after two PML cases were discovered -- and
relaunched it 16 months later with a risk evaluation and
mitigation strategy (REMS) in place.
[/quote]
The article can be seen here
HTML http://www.medpagetoday.com/Neurology/MultipleSclerosis/54704.
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