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#Post#: 184--------------------------------------------------
(Lancet) Cladribine and other new MS treatments--at what long-te
rm risk?
By: agate Date: February 22, 2014, 12:47 pm
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The Lancet Neurology, vol. 13, March 2014, pp. 235-37, contains
a short article in its "Comments" section, "New treatments for
multiple sclerosis: at what long-term risk?" focusing on
Cladribine and including a statement about proceeding with
caution when it comes to the newer MS drugs. A few excerpts:
[quote]
In The Lancet Neurology, Thomas Leist and colleagues present
the results of the ORACLE MS study and conclude that oral
cladribine delays conversion from a first clinical demyelinating
event to clinically definite MS.
Cladribine is a chemotherapeutic drug approved
for the treatment of hairy-cell leukaemia. Short
courses of cladribine induce prolonged lymphopenia
by selectively interfering with DNA synthesis and
repair in T and B lymphocytes. Because of this
immunosuppressive effect, cladribine has been studied
as a treatment for MS. Although cladribine was not
clinically effective for progressive MS, results from a
large 96-week placebo-controlled trial of two different
dose regimens of oral cladribine showed significant
benefits in relapsing-remitting MS. However, patients
receiving cladribine had a high incidence of prolonged
lymphopenia, a significant number of herpes zoster
infections, a fatal exacerbation of latent tuberculosis,
and three malignancies, one of which was fatal.
Because of the prolonged lymphopenia associated
with cladribine, and the potential long-term risks of
malignancy and infections, both the US and European
regulatory agencies refused to approve cladribine for
the treatment of relapsing-remitting MS.[/quote]
[The authors go on to summarize and comment on an article by
Leist et al. in the same issue of Lancet Neurology, "Effect of
oral cladribine on time to conversion to clinically definite
multiple sclerosis in patients with a first demyelinating event
(ORACLE MS): a phase 3 randomised trial."]
[quote]
Although cladribine delays conversion to clinically
definite MS after an initial demyelinating event and is
effective for treating relapsing-remitting MS, its safety
profile is a cause of concern. All medications, including
MS disease modifying therapies, come with risks. But
risks of treatment must be weighed against the risks
of the natural history of the disease. When treating
potentially fatal malignancies with a restricted armamentarium
of effective therapies, substantial risks are
acceptable. When treating MS, a disease that is rarely
fatal, has a highly variable course, and lasts decades
after diagnosis, the wisdom of accepting serious risks
such as opportunistic infections and malignancies
is questionable. The first generation of MS disease modifying
therapies such as the beta interferons and
glatiramer acetate are inconvenient since they require
self-injections. However, they are efficacious and have
proven to be safe for more than 20 years. We have not
been so fortunate with some subsequent therapies.
Mitoxantrone, a chemotherapeutic drug that suppresses
B-cell and T-cell activity, is effective for MS
but comes with the initially underappreciated longterm
risks of heart failure and treatment-related acute
leukaemia.
Natalizumab was released to market and
shortly thereafter was associated with development
of progressive multifocal leukoencephalopathy.
The lesson from these MS treatments is that we
should be cautious in embracing new treatments
that suppress the immune system and thus carry with
them unknown long-term risks. In this context, the
potential risks of cladribine seem to us to outweigh
the convenience of taking pills to achieve MS disease
control similar to that obtained with safer, yet less
convenient, treatments.
__________
Michelle H Cameron, Dennis Bourdette
Oregon Health & Science University, Neurology, 3181 SW Sam
Jackson Park Rd, Portland, OR 97239, USA
bourdett@ohsu.edu
MHC has received consultation and speaker honoraria from Acorda
Therapeutics and research support from the National MS Society,
the MS International Federation, the Collins Medical Trust,
Acorda Therapeutics, and the Department
of Veterans Affairs.
DB has received consultation and speaker honoraria from
Teva Neuroscience, Biogen Idec, Elan Pharmaceutical, and
Genzyme.
Published Online
February 5, 2014
This online publication has
been corrected.
The corrected version first
appeared at thelancet.com/
neurology on February 18,
2014
[/quote]
[Reference notes omitted.]
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