Interferon benefits early multiple sclerosis.Maybe yes, maybe no.

[Lady]

Interferon benefits early multiple sclerosis
Wed Oct 4, 2006 10:14 PM ET



By Will Boggs, MD

NEW YORK (Reuters Health) - Early and ongoing treatment with interferon beta-1a can provide lasting benefits to patients with relapsing-remitting multiple sclerosis (MS), according to a report in the journal Neurology.

Multiple sclerosis is thought to be an autoimmune disease, a disease that occurs when the body's own immune system attacks a key protein covering on the nerves, resulting in serious movement problems and other symptoms.

With relapsing-remitting MS, the initial form of the disease in 85 percent of patients, MS attacks are separated by periods of relatively normal function.

"Long-term treatment with (interferon beta-1a) is feasible and tolerated by most patients with some evidence of sustained benefit regarding clinical disease progression and MRI related outcomes," Dr. Ludwig Kappos from University Hospital Basel, Switzerland told Reuters Health.

Kappos and colleagues report follow-up data for up to 8 years after entry of patients into the Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study.

Early treatment with interferon beta-1a, particularly at a high dose, helped prevent disease relapses, the researchers note. Moreover, early treatment appeared to slow long-term disease progression based on MRI findings.

Treatment with interferon was generally well tolerated, the investigators say, with no new safety concerns.

"This trial represents another enormous expenditure of effort to determine whether we are helping our relapsing-remitting MS patients with existing therapies," writes Dr. John H. Noseworthy from the Mayo Clinic College of Medicine, Rochester, Minnesota in a related editorial.

"I respect this effort," Noseworthy concludes, "but am cautious about the authors' conclusions that 'patients with relapsing-remitting MS can experience sustained benefit over many years from early interferon beta-1a...three times weekly therapy.' Perhaps this is true (I hope it is), but the evidence is not yet fully convincing to me."

Kappos responded: "Noseworthy is correct in that this study did only provide indicative evidence for efficacy as it did not have an untreated (comparison) group from year 3 onwards and because at the end of the day we do not know what the impact of those patients who did not complete the follow-up would have been."

Nonetheless, he concluded, "Justification of early treatment with interefron-beta...is not only based on this observation but also on data from early treatment studies and from new insights in the neuropathology of early and late phases of MS."

SOURCE: Neurology, September 2006.

http://today.reuters.com/news/articlenews.aspx?type=healthNews&storyID=2006-10-05T021351Z_01_TON508004_RTRUKOC_0_US-MS-INTERFERON.xml&WTmodLoc=NewsArt-L3-Health+NewsNews-3

[Cat Dancer]

So, if someone is willing to take the risk -- they have MS, right now it's relatively mild, so they're going to skip the meds, great...but it's not a risk *I'm* willing to take! Knowing all-too-well what just one serious exacerbation can bring (in my case, serious disability), it's not a viable risk.

[Lady]

Cat, I agree. Early treatment should be considered. Preventing attacks and progression is important.

But we know for fact that "Mayo Clinic College of Medicine" has taken the argument up that to wait and see if their patients with early MS attacks get worse, and then give the treatment options..
Lady

[lady_express_44]

Early treatment with interferon beta-1a, particularly at a high dose, helped prevent disease relapses, the researchers note. Moreover, early treatment appeared to slow long-term disease progression based on MRI findings.

Does anyone know what they mean by "early treatment appeared to slow long-term disease progression based on MRI findings"? How might they define disease progression based on our MRI findings?

As for a "reduction in relapses rates", do we know for a fact that this is really a good thing?

Curr Med Chem. 2006;13(19):2329-43.

Current status and future prospective of immunointervention in multiple sclerosis

Cavaletti G.
Dipartimento di Neuroscienze e Tecnologie Biomediche, Universita di Milano Bicocca, Via Cadore 48 - 20052 Monza (MI), Italy. guido.cavaletti@unimib.it.

Multiple sclerosis (MS) is a complex neurological disorder characterized by inflammation and degeneration of the central nervous system, primarily involving the white matter.

On the basis of a wide body of evidence in experimental models and in affected patients, several attempts to treat MS using drugs which modulate immune reactions have been performed or are currently ongoing.

However, it should be stressed that inflammation does not have only a detrimental effect in MS. In fact, parts of the inflammatory events are crucial for the control and conclusion of the acute phase of damage and it is probable that they actually favor regeneration and recovery.

Due to the above, several trials with immunosuppressant drugs failed or were suspended because of unexpected worsening of the course of MS.

The knowledge of MS immunopathogenesis is so rapidly evolving that any attempt to review it is in some way frustrating. On the other hand, this evolution is at the basis of the several new treatment options which can be hypothesized for this disease.

The current status of immunosuppression in MS and the possible future development of MS treatment will be reviewed, with particular reference to those treatments which have already been tested in clinical trials and which are based on sound evidence of a putative interference with specific events occurring in MS, with the sparing of general immunity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16918358&dopt=Citation

Cherie

[xo++]

Noseworthy certainly has valid reservations about the study: 30% of the people originally in the study (http://www.neurology.org/cgi/content/abstract/67/6/944) were not available for long-term followup, and of course the study became open label. How well or poorly this 30% fared could dramatically affect the statistics, and it seems more likely that the 30% did poorly than well.

Nevertheless, shorter, double-blinded studies of interferons (CHAMPS study (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11006365&query_hl=1&itool=pubmed_docsum) and the comparable Rebif study (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=11377645)) have conclusively demonstrated that interferons delay conversion from a clinically isolated syndrome suggestive of MS to clinically definite MS (when considered across a population).

ECTRIMS provides two further studies regarding early use of interferons. One study looks at the CHAMPS clinical trial under a new light. Patients with a milder presentation or fewer lesions benefitted the most in terms of delaying conversion to clinically definite MS, but all groups benefitted.

A double-blinded, placebo controlled, Iranian study of 200 people who presented with a syndrome suggestive of MS, with positive MRI evidence, found that after three years, 57% of the placebo group but only 38% of the Avonex group had converted to clinically definite MS.

Cherie, I haven't read the paper (only the abstract) so I can't say what they meant -- the abstract states that there were no differences between groups on an MRI measure of brain atrophy (BPF), but treatment favorably impacted T2 burden of disease. The abstract also states that EDSS was lower in the original treatment group (but that's a clinical measure not an MRI measure).

Thanks for the post FL. :)

Mark

Intramuscular interferon beta-1a delays conversion to clinically definite multiple sclerosis in patients with a clinically isolated syndrome: subgroup analyses based on new diagnostic criteria

R.P. Kinkel, P.W. O'Connor, M. Kremenchutzky (Boston, USA; Toronto, London, CAN)

In CHAMPS, treatment with intramuscular (IM) interferon (IFN) beta-1a (30 mcg once weekly) significantly delayed conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) (adjusted hazard ratio 0.49, 95% CI 0.33, 0.73; p<0.001).

Patients who participated in CHAMPS were characterized as monosymptomatic on the basis of the predominant symptom of their presenting syndrome; asymptomatic signs identified upon neurologic examination reflecting multifocal involvement were not taken into account. Recent changes to diagnostic criteria and interpretations of presenting symptoms have been incorporated into the description of patients participating in some early treatment trials.

The purpose of this study was to use a new standardised classification scheme for a reanalysis of the CHAMPS study population. Patients’ presenting syndromes were assessed using an algorithm derived from Uitdehaag and colleagues (2005), which employed a stepwise neurologic evaluation. Patients were reclassified as monofocal or multifocal.

The ability of IM IFN beta-1a to delay progression to CDMS in subgroups based on disease onset (monofocal, multifocal) and baseline magnetic resonance imaging (MRI) characteristics, including number of T2 lesions (<9, >=9) and presence of gadolinium-enhancing (Gd+) lesions (0, >=1) was assessed.

Although all patients were considered monosymptomatic at CHAMPS randomisation, 30% of patients were classified as multifocal on reanalysis. Over 3 years of IM IFN beta-1a treatment, monofocal patients experienced a greater reduction in risk of developing CDMS than multifocal patients (52% vs 24%).

Patients with <9 T2 lesions at baseline experienced a greater reduction in risk of developing CDMS than those with >=9 baseline T2 lesions (58% vs 38%). Risk reductions were lower for patients lacking Gd+ lesions at baseline than for patients with at least 1 baseline Gd+ lesion (37% vs 66%).

The treatment effect was consistent for all different subgroups (p>0.05 for the interactions). Two-year results will also be presented. IM IFN beta-1a was effective when initiated at the time of a first demyelinating attack whether the disease was clinically monofocal or more disseminated, either by clinical or MRI criteria.

IM IFN beta-1a effectively prolongs time to conversion to CDMS in patients with early disease as defined by an updated evaluation of presenting symptoms. This finding is consistent with that of the original CHAMPS analysis.


Effect of early interferon-beta1-a therapy on conversion to clinically definite multiple sclerosis in Iranian patients with a first demyelinating event

H. Pakdaman, A. Fallah, R. Pakdaman, A. Shirani, M. Sahraian (Tehran, IR)

Background: Interferon beta has been shown to reduce clinically assessed and MRI- measured disease activity in multiple sclerosis (MS). Two recent studies have demonstrated a delay in conversion of patients to MS using interferon beta-1a. The goal of this study was to assess the effect of early treatment with interferon beta-1a (Avonex) on the risk of conversion to clinically definite MS in Iranian patients.

Methods: This was a multi-centre double-blind placebo-controlled randomized trial. Eligible patients had presented with a first episode of neurological dysfunction suggesting MS within the previous 3 months and had positive brain MRI Scan.

Patients were randomly assigned interferon beta-1a (Avonex) 30 µg or placebo intramuscularly once weekly for 3 years. Neurological and clinical assessment and brain MRI scan was done on a regular basis. The primary outcome measure was conversion to clinically definite MS.

Results: 200 completed the study. Fewer patients converted to clinically definite MS in the Avonex group than in the placebo group during the 3-year study (36% vs. 57%, p<0.003). The number of new or enlarging T2-weighted MRI lesions and T1-weighted enhancing lesions were significantly lower in Avonex group.

Conclusion: Avonex treatment at an early stage of MS delays conversion to clinically definite MS and is recommended in Iranian patients as well. It has also positive effects on clinical and MRI outcomes.