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#Post#: 184--------------------------------------------------
(Lancet) Cladribine and other new MS treatments--at what
long-term risk?
DIR 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.
--- End 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
>
>
--- End Quote ---
[Reference notes omitted.]
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