RE: autoimmune digest

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1. Recent MS MEDLINE Abstract(s)

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Date: Mon, 17 Nov 2003 13:29:18 -0500

From: Irwin Mortman <irwin@...>

Subject: Recent MS MEDLINE Abstract(s)

1: Lancet. 2003 Nov 8;362(9395):1517-1526. Related Articles, Links

Cannabinoids for treatment of spasticity and other symptoms

related to multiple sclerosis (CAMS study): multicentre randomised

placebo-controlled trial.

Zajicek J, Fox P, H, D, Vickery J, Nunn A, A.

Peninsula Medical School, Plymouth, UK

Background Multiple sclerosis is associated with muscle

stiffness, spasms, pain, and tremor. Much anecdotal evidence suggests

that cannabinoids could help these symptoms. Our aim was to test the

notion that cannabinoids have a beneficial effect on spasticity and

other symptoms related to multiple sclerosis.Methods We did a

randomised, placebo-controlled trial, to which we enrolled 667

patients with stable multiple sclerosis and muscle spasticity. 630

participants were treated at 33 UK centres with oral cannabis extract

(n=211), Delta(9)-tetrahydrocannabinol (Delta(9)-THC; n=206), or

placebo (n=213). Trial duration was 15 weeks. Our primary outcome

measure was change in overall spasticity scores, using the Ashworth

scale. Analysis was by intention to treat.Findings 611 of 630

patients were followed up for the primary endpoint. We noted no

treatment effect of cannabinoids on the primary outcome (p=0.40). The

estimated difference in mean reduction in total Ashworth score for

participants taking cannabis extract compared with placebo was 0.32

(95% CI -1.04 to 1.67), and for those taking Delta(9)-THC versus

placebo it was 0.94 (-0.44 to 2.31). There was evidence of a

treatment effect on patient-reported spasticity and pain (p=0.003),

with improvement in spasticity reported in 61% (n=121, 95% CI

54.6-68.2), 60% (n=108, 52.5-66.8), and 46% (n=91, 39.0-52.9) of

participants on cannabis extract, Delta(9)-THC, and placebo,

respectively.Interpretation Treatment with cannabinoids did not have

a beneficial effect on spasticity when assessed with the Ashworth

scale. However, though there was a degree of unmasking among the

patients in the active treatment groups, objective improvement in

mobility and patients' opinion of an improvement in pain suggest

cannabinoids might be clinically useful.

PMID: 14615106 [PubMed - as supplied by publisher]

2: Lancet. 2003 Nov 8;362(9395):1513. Related Articles, Links

Oral cannabinoids for spasticity in multiple sclerosis: will

attitude continue to limit use?

Metz L, Page S.

Department of Clinical Neurosciences, Foothills Medical Center,

Alberta, T2N 2T9, Calgary, Canada

PMID: 14615102 [PubMed - as supplied by publisher]

3: Neurology. 2003 Nov 11;61(9):1303-4. Related Articles, Links

Multiple sclerosis presenting as lower motor neuron wasting and

weakness of the distal upper extremity.

Chong PS, Vucic S, Cros DP.

Massachusetts General Hospital, Boston.

PMID: 14610149 [PubMed - in process]

4: Neurology. 2003 Nov 11;61(9):1245-1249. Related Articles, Links

alphaB-Crystallin genotype has impact on the multiple sclerosis

phenotype.

Van Veen T, Van Winsen L, Crusius JB, Kalkers NF, Barkhof F, Pena

AS, Polman CH, Uitdehaag BM.

Departments of Neurology (Drs. van Winsen, Kalkers, Polman, and

Uidehaag, T. van Veen) and Clinical Epidemiology and Biostatistics

(Dr. Uidehaag, T. van Veen), Laboratory of Immunogenetics (Dr. Pena,

J.B.A. Crusius), and MS-MRI Center (Dr. Barkhof), VU University

Medical Center, Amsterdam, the Netherlands.

BACKGROUND: Both multiple sclerosis (MS) susceptibility and MS

clinical phenotype are in part genetically determined.

alphaB-Crystallin is a candidate autoantigen in MS, and there are

three polymorphisms in the promoter region of the encoding gene

(CRYAB): at positions -C249G, -C650G, and -A652G. METHODS: These

polymorphisms were studied in sporadic cases of MS, assessing disease

susceptibility, clinical phenotype, and MRI appearance. RESULTS: The

CRYAB polymorphisms influenced susceptibility as well as disease

expression in MS. CONCLUSION: rs of the rare allele CRYAB-650*C

had an increased likelihood of a noninflammatory, neurodegenerative

phenotype characterized by a relatively rapid, primary progressive

clinical disease course.

PMID: 14610128 [PubMed - as supplied by publisher]

5: Neurology. 2003 Nov 11;61(9 Suppl 5):S35-7. Related Articles, Links

Statistical approaches to assessing the effects of neutralizing

antibodies: IFNbeta-1b in the pivotal trial of relapsing-remitting

multiple sclerosis.

Petkau AJ.

Department of Statistics, University of British Columbia,

Vancouver, British Columbia, Canada.

Carefully conducted large-scale clinical trials have provided

strong evidence that type I interferons favorably influence clinical

and MRI outcomes in patients with multiple sclerosis. Some patients

develop neutralizing antibodies (NAbs) to these treatments,

reflecting an immune system response. The clinical significance of

these NAbs has been uncertain because titers vary widely, and even

highly elevated NAb titers decrease to undetectable levels in some

patients. Whether NAbs decrease the efficacy of these treatments is a

critically important scientific question. We argue that a

longitudinal data analysis is the most appropriate approach to

address this question.

PMID: 14610111 [PubMed - in process]

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End of AUTO-IMMUNE Digest - 13 Nov 2003 to 17 Nov 2003 (#2003-116)