WHO - Statins may induce upper motor neurone lesions

[xrn]

Hello to all. A brief note about this issue looks as if it is starting to grab appropriate attention. It is inevitable that enough case reports will cause a change in approach and it saddens me that so many people have to be harmed before anyone takes notice. Nevertheless, I am glad to learn of this report.

Kind regards,
xrn

Drug Saf. 2007;30(6):515-25.
Statins, neuromuscular degenerative disease and an amyotrophic
lateral sclerosis-like syndrome: an analysis of individual case
safety reports from vigibase.Edwards IR, Star K, Kiuru A.

The WHO Foundation Collaborating Centre for International Drug
Monitoring, the Uppsala Monitoring Centre (UMC), Uppsala, Sweden.

BACKGROUND:
The WHO Foundation Collaborating Centre for International Drug Monitoring (Uppsala Monitoring Centre [UMC]) has received many individual case safety reports (ICSRs) associating HMG-CoA reductase
inhibitor drug (statin) use with the occurrence of muscle damage, including rhabdomyolysis, and also peripheral neuropathy. A new signal has now appeared of disproportionally high reporting of upper motor neurone lesions.

AIM AND SCOPE:
The aim of this paper is to present the upper motor neurone lesion cases, with other evidence, as a signal of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like syndrome. The paper also presents some arguments for considering that a spectrum of severe neuromuscular damage may be associated with statin use, albeit rarely.

The paper does not do more than raise the signal for further work and analysis of what must beregarded as a potentially very serious and perhaps avoidable or reversible adverse reaction, though it also suggests action to be taken if an ALS-like syndrome should occur in a patient using
statins.

METHODS: The 43 reports accounting for the disproportional reports in Vigibase (the database of the WHO Programme for International Drug Monitoring) are summarised and analysed for the diagnosis of an ALS-like syndrome. The issues of data quality and potential reporting bias are considered.

RESULTS: 'Upper motor neurone lesion' is a rare adverse event reported in relationship to drugs in Vigibase (a database containing nearly 4 million ICSRs). Of the total of 172 ICSRs on this reported term, 43 were related to statins, of which 40 were considered further: all but one case was reported as ALS. In 34/40 reports a statin was the sole reported suspected drug. The diagnostic criteria were variable, and seven of
the statin cases also had features of peripheral neuropathy. Of a total of 5534 ICSRs of peripheral neuropathy related to any drug in Vigibase, 547 were on statins. The disproportional reporting of statins and upper motor neurone lesion persisted after age stratification, and such disproportionality was not seen for statins and Parkinson's disease, Alzheimer's disease, extrapyramidal disorders, or multiple sclerosis-like syndromes.

DISCUSSION:
Because the cases were sometimes atypical we propose the use of the term 'ALS-like syndrome' and speculate whether this is part of a spectrum of rare neuromuscular damage. The diagnosis of ALS is often problematic, and the insidiousness and chronicity of the disease make causality with a drug difficult to assess. The disproportionally high reporting makes this an important signal nevertheless, since ALS is serious clinically and statins are so widely used. Wide use of the statins also makes a chance finding more probable, but is unlikely to cause disproportional reporting when there are no obvious biasesidentified.

CONCLUSION: We emphasise the rarity of this possible association, and also the need for further study to establish whether a causal relationship exists. We do advocate that trial discontinuation of a statin should be considered in patients with serious neuromuscular disease such as the ALS-like syndrome, given the poor prognosis and a possibility that progression of the disease may be halted or even reversed.

PMID: 17536877 [PubMed - in process]

[carbuffmom]

Hi xrn:

Wow! Thanks for the great info. I am seeing an ALS specialist tomorrow. I have printed it and am going in armed with this new info. I will keep you posted. Thanks.

DEB

[xrn]

xrn:
Hi Deb. I thought it would be of interest. I wish you the very best for your meeting tomorrow. This stuff is very hot off the presses so don't be surprised if the specialist does not have knowledge of this. It ought to help you to make a case that should ring loud alarm bells, if your ALS specialist reads this information.

Kind regards,
Jeff

[Biologist]

That's MAJOR !

Thanks, xrn.

Biologist

[cjbrooksjc]

All: Ever tire of wrestling with a complex problem so long you get frustrated, walk down the hall into another's office or pick up the phone and begin to explain why you are stumped; then, halfway through, feel epiphany rising over your shoulder with answers you hadn't considered alone? That's what this forum has been like for me. The websites I get introduced to by the Spacedoc membership prompt me to think, and I can't say how grateful I am for all the invaluable bits of information I have gleaned over the last few months just by having someone to use as a sounding-board while that thinking process goes on... I'd like to add my thanks to ALL THOSE who take the time to investigate and contribute; there are just too many to list; you know who you are. (actually I'm worried I'll forget to mention someone) Be assured I know who you are!

Best regards,

Brooks