• Beta interferon 1a - known by the trade names AVONEX® and REBIF®
• Beta interferon 1b - known by the trade name  BETASERON®, EXTAVIA
• Glatiramer acetate  - known by the trade name COPAXONE® and the generic names GLATIMER^® and CAPAXON R
• Natalizumab - known by the trade name TYSABRI^®

Below you will find any general news stories with regards Disease Modifying Drugs.

You can access all the latest research news about Disease Modifying Drugs by going the Disease Modifying Drugs Ongoing Research page.

As chair of the Scientific Advisory Committee (SAG) of the Multiple Sclerosis Risk Sharing Scheme I strongly reject the suggestion that our advice is based on any considerations other than scientific rigour.¹

Members of DH and of the 4 companies attend meetings with observer status only. Final decisions relating to the scheme, e.g. on whether to apply price adjustments at any point, are taken between the parties to the scheme informed by advice from my committee.

I have no doubt that the scientific advice for which the SAG was responsible was correct – it would have been unsafe to draw any conclusions about the effectiveness of the MS drugs from the result of the two year follow up. The reasons for this conclusion are well set out in the BMJ paper describing these two year results.²

They relate in large part to the construction and interpretation of the counter-factual data-set (the data-set with which the RSS data were compared). It turned out that the scheme did not have access to the raw counterfactual data but only to data derived from the raw data.

Moreover it proved impossible to work out precisely how the derived data had been calculated from the raw data. The upshot is that we did not know how exactly to mimic the derivation process so that the two data sets could be compared on a level playing field.

For this and other reasons, I wrote to the Department of Health before the data analysis was undertaken to say that I did not think a valid comparison could be made at the two year point and to say that we were searching for an alternative counterfactual data set more suited to this particular purpose.

McCabe and colleagues ³ imply that biases can not explain the results later obtained but they are wrong, since the sensitivity analyses show that the conclusions can be reversed according to the assumptions made (only a proportion of which were discussed by McCabe). Do these authors really think that an uncertain analysis based on observational data at two years should trump the RCT results at the same time period?

The SAG is charged only with providing scientific advice on the risk sharing scheme. However, I would like to respond to some of the policy related comments in the critical articles as citizen, albeit with experience of the scheme.

I discern two broad policy relevant criticisms:

1. The price of the drugs should have been adjusted (downwards) notwithstanding the uncertain parameter estimates mentioned above.

2. The Risk Sharing Scheme was a bad idea.

Regarding the price adjustment (or lack thereof) critics argue that the rules determining price adjustment had been set in advance and hence the price should have been adjusted on the basis of the observed data quite irrespective of the massive sensitivity of the estimate of effectiveness to un-testable assumptions in the analysis plan. Since the methodology for the scheme had not been worked out when it was agreed in 2002,

I understood that one of the functions of the SAG was to advise the scheme on the validity of interim results. The results were silent on the actual effectiveness of the drugs which is what the parties to the agreement were betting on. At least in retrospect this was an unsound bet, since neither side understood the risks to which tax-payers and share-holders were exposed. Nullifying a bet is only a bad idea if it can lead to ‘moral hazard’. That can only arise if the intention is to repeat wagers of this type.

This takes me to the second point – the suitability of price adjustment schemes. I have some sympathy with Raftery’s argument that such schemes are a poor policy instrument and, if used at all, I do not think that they should be used for short term decision making.

My reluctance to accept observational data to measure effectiveness has been reinforced by the fiendish methodological difficulties encountered by this risk sharing scheme.

However, the story is not yet fully told – we have read only the first of five exciting instalments. Follow up in the clinical trials on which a licence was granted averages about two years. Cost-effectiveness estimates are based on a model in which the two year data are extrapolated over ten years. This model is more sensitive to long term outcomes than to outcomes at two years. Observations over 10 years of follow up will be a substantial improvement on extrapolation of data from trials that followed patients up for only two years. Moreover the risk sharing scheme plans to base further analysis on an alternative counter- factual data set that the SAG believes will overcome some of the difficulties described in the BMJ article, since we will now have access to raw data.

The study will provide important prognostic data along with information on the relationship between short and long term effectiveness. Such data are available for the common cancers but not for multiple sclerosis.⁴ In summary, I advocate long term observational studies when trials have been truncated before the collection of the most important long term data and I agree with Raftery that price adjustment mechanisms are a poor policy instrument for short term price adjustment.

¹. Raftery J Multiple sclerosis risk sharing scheme: a costly failure. BMJ 2010;340:C1672

². Boggild M, Palace J, Barton P, Ben-Shlomo Y, Bregenzer T, Dobson C, Gray R. Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator. BMJ. 2009;339:b4677.

³. McCabe et al. Continuing the multiple sclerosis risk sharing scheme is unjustified. BMJ 2010;340:C1786

⁴. Bowater RJ, Bridge LJ and Lilford RJ. The relationship between progression- free and post-progression survival in treating four types of metastatic cancer. Cancer Letters 262(1): 48-53; 2008.

Competing interests: I am chair of the Scientific Advisory Committee to the risk sharing scheme

Richard J Lilford,
Prof of Clinical Epidemiology
University of Birmingham

Source: British Medical Journal © 2010 BMJ Publishing Group Ltd. (08/06/10)

The scheme involved four drugs for multiple sclerosis launched in the 1990s, Biogen Inc's Avonex, Bayer's Betaseron, and Merck KGaA's Rebif, as well as Copaxone from Israel's Teva Pharmaceuticals, which were hailed as the first treatment to delay progression of the disabling neurological condition that affects 100,000 people in the UK.

It was set up in 2002 after the National Institute for Clinical Excellence (Nice) unexpectedly ruled that the drugs were not cost effective and should not be used on the NHS. To head off opposition from patient groups and the pharmaceutical industry, the Department of Health established the largest NHS "patient access scheme", to provide patients with the drugs, costing an average £8,000 a year, on the understanding that if they turned out to be less effective than expected, the drug companies would reduce the price.

The first report on the outcome was due after two years but was not published until last December, seven years later. It showed that the drugs failed to delay the onset of disability in patients – defined as walking with a stick or using a wheelchair – and may even have hastened it. On that basis, the drug companies would have had to pay the NHS to use them to make them cost effective.

Despite this finding, the price was not reduced and the scientific advisory group monitoring the scheme advised that "further follow up and analyses" were required. It said that disability may yet improve, the disease may have become more aggressive and the measure of disability used may have underestimated benefit. There were 5,583 patients in the scheme at a cost to the NHS of around £50m a year, amounting to £350m over seven years to 2009. The Multiple Sclerosis Society said twice as many patients were using the drugs outside the trial, implying a total NHS cost of £700m for a treatment that does not work.

In a series of articles in today's British Medical Journal, experts criticise the scheme. James Raftery, professor of health technology assessment at the University of Southampton and an adviser to Nice, said the scientific advisory group included representatives from the four drug companies, two MS groups, and the neurologists treating patients, all of whom had lobbied for the continued use of the drugs on the NHS.

"The independence of this group is questionable," he said. "Monitoring and evaluation of outcomes must be independent. Transparency is essential, involving annual reports, access to data, and rights to publish. Any of these might have helped avoid the current fiasco."

"The scheme was a success for the drug companies, who sold at close to full price to the NHS. For the NHS, however, the scheme can be judged only a costly failure."

Professor Christopher McCabe, head of health economics at the University of Leeds, writing with colleagues in the BMJ, said: "None of the reasons for delaying the price review withstand critical assessment." Professor McCabe told The Independent: "We should be asking questions about paying for these drugs. In terms of disability avoidance, the evidence is not there."

Alastair Compston, professor of neurology at the University of Cambridge, defended the scheme. He said that despite a disappointing outcome, the scheme had "advanced the situation for people with multiple sclerosis" by improving understanding and care of the disease. Neil Scolding, professor of neurosciences at the University of Bristol, said the proportion of British patients treated with drugs (10-15 per cent) was tiny compared to France and Germany (40-50 per cent). He said the scheme had also led to the appointment of 250 multiple sclerosis nurses.

"[Though] expensive and flawed, if it turns out to have been no better than a clever wooden horse, then the army of MS healthcare specialists it delivered may make it more than worthwhile," he wrote. The MS Society claimed success for the scheme up to 2007 but after publication of the results last December, withdrew its support.

MS: why the drugs don't work

Multiple sclerosis is a chronic disease. It may take 40 years to run its course. In developing drugs to slow its progression, doctors have used brain scans to show lesions which the drugs appeared to prevent, and gave quicker results. Some experts thought the lesions were the disease but little effort was made to check. But preventing lesion formation does not prevent disability caused by the condition. The drugs deal with the lesions, not the disease.

Multiple sclerosis risk sharing scheme: a costly failure - full BMJ article.

Source: The Independent Copyright 2010 Independent Print Limited  & Reuters © Thomson Reuters 2010 (04/06/10)

Biogen Idec Inc., the world’s largest maker of medicines for multiple sclerosis, sued Bayer AG, Pfizer Inc., and Merck KGaA’s Serono unit for patent royalties on drugs similar to its Avonex treatment.

Biogen Idec claims the drugs Rebif promoted by Pfizer and Serono, Bayer’s Betaseron, and a version sold by Novartis AG as Extavia infringe a patent issued in September. The complaint was filed May 28 in federal court in Newark.

“We believe our patent covers Avonex and other beta interferon treatments for multiple sclerosis,’’ said Christina Chan, a Biogen Idec spokeswoman. “We did offer to license this patent to other makers of beta interferon MS products, but no agreement was reached.’’

Avonex generated $2.3 billion in sales last year, 53 percent of Cambridge, Mass.-based Biogen Idec’s revenue. Bayer, Germany’s largest drug maker, filed a lawsuit May 27 in the same court, seeking a ruling that the patent is invalid or not infringed.

Biogen Idec has demanded royalties of as much as 8.5 percent on sales of Betaseron, which generates more than $1 billion a year in revenue, Bayer said in its complaint.

Rebif, sold by New York-based Pfizer and Darmstadt, Germany-based Merck, had global sales of $2.14 billion in 2009, according to Bloomberg data.

Novartis received approval last year to sell Extavia and pays royalties to Leverkusen, Germany-based Bayer. Novartis, based in Basel, Switzerland, said Extavia generated $20 million in sales in the first quarter.

Source: Boston.com © Copyright 2010 Globe Newspaper Company (02/06/10)

The European Medicines Agency has been formally notified by BioPartners GmbH of its decision to withdraw its application for Biferonex (interferon beta-1a), 6 million-international-unit solution for injection, prefilled syringes for subcutaneous administration.

Biferonex was expected to be used to treat patients with relapsing-remitting MS.

The application for the marketing authorisation for Biferonex was submitted to the Agency on 24 July 2007. On 19 February 2009, the Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation. Following this, the company requested a re-examination of the opinion, which was under review by the CHMP at the time of the withdrawal.

The company stated in its official letter that its decision to withdraw the application was based on the fact that the additional information provided in support of the re-examination had not changed the Committee's view on the benefit-risk balance of Biferonex.

More information about Biferonex and the state of the scientific assessment at the time of withdrawal will be made available in a question-and-answer document. This document, together with the withdrawal letter from the company, will be published on the Agency's website after the next CHMP meeting of 22-25 June 2009.

Source: Medical News Today © 2009 MediLexicon International Ltd (01/06/09)

Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS.

Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis (MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments.

Results: Centres consented 5560 patients.

Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively.

Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies.

Conclusions: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives.

However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed.

Author: Mark Pickin, Cindy L Cooper, Timothy Chater, Anthony O'Hagan, Keith R Abrams, Nicola J Cooper, Mike Boggild, Jackie Palace, George Ebers, James B Chilcott, Paul Tappenden and Jon Nicholl

Source: BMC Neurology 2009, 9:1 (06/01/08)

A lack of funding has forced a Cardiff-based MS service to start a waiting list for patients who could benefit from beta interferon and copaxone.

Experts told the Western Mail that Health Commission Wales has also told the South Wales MS service to become more “efficient” to ensure more patients can be treated. But without adequate funding the service could be forced to cut back.

The funding crisis comes just a year after the service, which is based at the University Hospital of Wales, was hit by a similar cash shortfall. Now experts are concerned there will not be enough money to pay for the latest MS treatment, Tysabri,  which was approved by the National Institute for Health and Clinical Excellence last week.

Dr Trevor Pickersgill, a consultant neurologist at the University Hospital of Wales, said, “The money has run out and we are building up a waiting list.”

Beta interferon and copaxone cost an average of £10,000 per patient per year for the treatment alone.

The latest MS drug to be approved for use on the NHS, Tysabri, costs £14,000 per year, but also requires patients who suffer from frequent severe attacks to be admitted to hospital 12 times a year for treatment.

It is thought that at least 20 patients in South Wales would benefit from taking Tysabri, which is twice as effective as beta interferon.

A WAG spokesman said, “These issues have been raised and we will look at these in detail.”

Source: ICWales.co.uk © owned by or licensed to Western Mail & Echo Limited 2007 (10/07/07)

Immunomodulatory agents (IMAs) could slow the progress of the disease, but are only prescribed in a minority of cases, and mostly by neurologists.

Jagannadha Avasarala from Kansas Neurological Consultants, Wichita analysed treatment trends between 1998 and 2004 for all Federal Drug Administration (FDA) approved IMA drugs, together with colleagues from Wake Forest University School of Medicine, NC, and Ohio State University Medical Center. They used National Ambulatory Medical Care Survey (NAMCS) data to evaluate prescribing trends as well as type of physician and geographic location.

Avasarala found that an estimated 6.7million MS patient visits occurred during the study timescale: 3.4 visits per 1000 persons each year. Women were seen four times as often as men and Caucasians had a higher visit rate than African Americans (90% vs 8%). This may because MS is more prevalent amongst Caucasian women than any one ethnic group.

Neurologists prescribed IMAs more often than family practitioners or internists, with urban patients visited neurologists than their rural counterparts. The NAMCS data showed that 62% of established MS patients evaluated by neurologists and 92% of those seeing family medicine practitioners or internists were not being treated with IMAs. The higher treatment rate among neurologists probably reflects greater awareness of these drugs and familiarity with MS cases.

"Strategies for educating both neurologists and non-neurologists about the benefits of initiating IMA use in MS patients and in continuing their use remain critical to improving long-term patient outcomes in treatment of MS" Says Avasarala.  (05/04/07)

Intended audience: Neurologists, GPs, patients, healthcare providers.

Publication history information: Published March 2007.

Access: Available to the general public. Portable Document File / PDF requiring Adobe Acrobat Reader.

Download Guidelines here: http://www.theabn.org/downloads/ABN-MS-Guidelines-2007.pdf

(31/03/07)

Interferon-beta is used for multiple sclerosis therapy. An interferon-beta protein developed at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany, in collaboration with CinnaGen company, Tehran, Iran, is now the first therapeutic protein from a Fraunhofer laboratory to be approved as biogeneric / biosimilar medicine. Multiple sclerosis (MS) is the most common disease of the central nervous system. Estimates put the number of people with multiple sclerosis at about 2.5 million worldwide.

The only therapeutic successes achieved so far have been with interferon-beta, a protein produced naturally in the body. It slows down the progression of the illness and reduces the relapse rate. Biotechnological techniques make it possible to engineer this endogenous protein in bacterial or mammalian cells. An interferon-beta-1a, whose biotechnical engineering and production up to the pilot scale was optimised at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in collaboration with CinnaGen Company, has now been approved as biogeneric by the Iranian Food and Drug Administration (IFDA). It is produced and marketed in Iran as CinnoVex by the biotech company CinnaGen.

IGB's project group "Genetic Engineering" under Professor Bernd Otto in Hannover, Germany, successfully cloned the human protein into a suitable expression vector and established the production of the natural protein by a stable transfection in a mammalian cell line. The interferon-beta-1a hereby obtained is glycosylated like the human protein. In vitro it shows a higher biological activity than interferon-beta-1b, which is produced in bacteria and is not glycosylated.

In the Fraunhofer IGB Stuttgart laboratories a multi-disciplinary team developed the production of the pharmaceutical protein up to pilot scale. "We have developed the fermentation process as well as the downstream processing, resulting in a highly purified protein. We identified the protein by amino acid sequencing and proved its antiviral effects," explains Professor Herwig Brunner, Director of Fraunhofer IGB. The Iranian CinnaGen gave proof of its clinical effectiveness within three years, including appropriate quality control and clinical trials.

Developing a medicine involves a great deal of time and expense.

"Fraunhofer supports pharmaceutical and biotechnology enterprises through the development and biotechnological production of generic proteins, as well as the development of new therapeutic proteins," Professor Brunner describes the IGB strategy. A more soluble variant of interferon-beta also engineered at the IGB is for example being clinically investigated by the Vakzine Projekt Management (VPM) GmbH in Braunschweig, Germany. In addition, functional genome and proteome analysis technologies established at IGB have led to a large number of potential target molecules for the therapy of infections by the pathogenic yeast Candida albicans and have thus opened possibilities for new medical drugs. Preclinical tests of promising active substance candidates can be supported by IGB's organoid test systems on the basis of three-dimensional human cell structures, thus helping to avoid animal testing. Further potential therapeutic peptides and proteins have been developed at Fraunhofer IGB, representing a good source for companies interested in filling their product pipeline.

Source: Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB (26/01/07)

The Department of Health has told NHS Trusts that they must continue to fund disease modifying drugs – the beta interferons (a and b) and glatiramer acetate – for people with MS who stand to benefit.

Stada Arzneimittel AG said it is no longer to pursue its Interferon-beta project to treat multiple sclerosis, as limited marketing opportunities did not justify completion of the project.

The company said that the project, which was launched in 2001, did not have a completion date or a potential peak sales figure.

Source: Forbes.com Copyright AFX News Limited 2006. All rights reserved.(21/11/06)

Wales Health Minister Dr Brian Gibbons today announced an additional £700,000 to meet the increasing demands for high cost drugs to treat Welsh patients with Multiple Sclerosis.

The £700,000 is additional to the existing annual allocation for Disease Modifying Therapies (DMTs) of £2.5million. The additional funds will be given to the hospitals that treat Welsh MS patients. This will help to ensure that all MS patients who are eligible for DMTs under the criteria set by the Association of British Neurologists can start treatment at the earliest opportunity.

Dr Gibbons said: “The demand for DMTs in Wales has increased beyond anticipated levels. It is because of this that I am announcing a further £700,000 to support people with MS in Wales.

“This decision has been reached after careful consideration of all issues relating to the provision of Disease Modifying Therapies for MS. This money will help patients who will really benefit from this treatment to start receiving it soon.

“We have considered a number of options to help resolve the growing difficulties associated with supplying DMTs to MS patients in Wales. We have decided that this additional money will be accompanied by a review of the latest evidence and research findings on managing and treating MS together with an assessment of the future epidemiological trends in MS in Wales.”

Source: onlineWales Internet copyright 1999-2006 (30/10/2006)

The Minister for Health and Social Services in Wales has finally agreed to find additional funding for the disease modifying drug therapies – beta interferons and glatiramer acetate.

Until now, a refusal to honour legal commitments led to many people in Wales being denied access to these drugs. MS patients who meet the prescribing criteria should now be able to start treatment as soon as is practical.

Leading scientists have raised serious concerns about a major government study into the effectiveness of drugs used by thousands of people with MS. The study was originally being conducted by an established team at Sheffield University.

But it has been switched to Parexel - a company with commercial links to three of the four pharmaceutical companies involved in the study.

The concerns are outlined in a report to be aired on BBC Radio Five Live.

There are also concerns about how much of the research will be made public.

It is feared patients currently taking expensive drugs like beta interferon may be kept in the dark even after the ten year study is complete.

The National Institute for Health and Clinical Excellence decided in 2001 not to sanction beta interferon - or another MS drug, glatiramer acetate - for use on the NHS, ruling they did not represent value for money.

However, after a sustained campaign by the pharmaceutical companies, charities and patients, the government rejected the advice of its own advisory body.

Long-term effect

Instead, they came up with an alternative approach known as the Risk Sharing Scheme.

Under its terms, the government committed around £500 million to providing the MS drugs over a ten year period while scientists studied their long-term effectiveness.

If the study reveals the drugs are not as effective as the pharmaceutical companies say, they will have to drop the price of their products to the NHS. The original contract to evaluate the progress of the thousands of MS patients on the scheme was given to the Sheffield team.

However, sources have told the BBC that the contract was re-tendered last year following a dispute over the university's right to publish independently on their findings.

Sir Iain Chalmers, editor of the James Lind Library, which reviews scientific research, is uneasy about the decision.

He said: "I think it's a totally unreasonable expectation, that information which may be important to patients and prescribers should potentially be suppressed because a company does not find it in its interests to see it made public".

'Not a veto'

One of the pharmaceutical companies involved in the scheme has denied that any of the research will be suppressed, even though each company in the risk sharing scheme has the right to decide if any research involving their own drugs should be published.

Pete Smith, managing director of Biogen Idec in the UK and Ireland, said: "It may look like a veto but it really isn't a veto.

"We are very confident that our drug is going to demonstrate its value here in the UK and to those patients who are in need of care and we are quite frankly looking forward to those results being published at the completion of this study."

The move to a commercial company has also dismayed one of the world's experts on Multiple Sclerosis whose research data was being used by the scientists at Sheffield University.

George Ebers, professor of clinical neurology at Oxford University, said: "I think you'd have to have a pretty good reason to change horses in the middle of what is a pretty rocky and rapid stream.

"One has a certain bit of worry here that you've got an academic group with a well-established and well earned reputation in this whole business and in particular MS, and then for reasons which I don't understand they're replaced by a clinical research organisation.

"I have reservations about this being a clinical research organisation that's going to be involved in determining efficacy."

Questions remain

Experts in the field of scientific research claim that any question marks hanging over the value of the MS drugs are unlikely to be satisfactorily answered by the study.

Sir Iain Chalmers said: "I think we remain, I would say, almost irresponsibly ignorant about what these drugs really do have to offer and I'm not confident that the current arrangements for so-called evaluation of the longer term effects of these drugs are actually going to produce reliable evidence."

The scheme was being overseen by a project management group that included the MS Trust charity, four pharmaceutical companies, the Department of Health and several others including scientists and academics.

However, the BBC understands that the group as a whole was not consulted about the decision to appoint Parexel, which was taken instead by the drugs companies, the Department of Health and the MS Trust.

The Five Live Report: Drugs On Trial will be broadcast within the Julian Worricker Show on Sunday, 30 July 2006, at 1000 BST on BBC Radio Five Live.

Source: BBC News Copywrite BBC 2006 (29/07/06)

An editorial accompanying a published debate on the pros and cons of starting treatment early in the course of multiple sclerosis comes down in favor of early treatment for this potentially devastating disease.

This opinion coincides with a consensus paper published by the US National MS Society.

The April issue of the Archives of Neurology features both sides of this debate on early treatment for MS.

Background: Currently five therapies are approved by the U.S. Food and Drug Administration for the treatment of multiple sclerosis. These agents can reduce future disease activity for many individuals with relapsing forms of MS, including those with secondary progressive disease who continue to have relapses. The National MS Society's Medical Advisory Board recommends that initiating MS therapy with an immunomodulating drug (such as FDA-approved interferons or glatiramer acetate) should be considered as soon as possible following a definite diagnosis of MS with a relapsing course, and for selected patients with a first attack who are at high risk for MS. Some clinicians disagree, however, choosing to defer treatment until the extent of disease activity is more clearly established.

The Debate: E. M. Frohman, MD, PhD (University of Texas Southwestern Medical Center at Dallas) and an international panel of coauthors present the following arguments in favour of early treatment in an article titled, "Most Patients with Multiple Sclerosis or a Clinically Isolated Demyelinating Syndrome Should Be Treated at the Time of Diagnosis" (Archive of Neurology 2006;63:614-619):

• Most who have MS will develop significant disability over time, and when MS is initially diagnosed, it is impossible to determine whether its course will be disabling or benign (mild course of disease).
• Studies show that injury to nerve fibres - which leads to the progression of disability that can occur in people with MS - begins early in the course of the disease. Even if a person appears to be doing well, with few clinical relapses, there may be evidence on MRI of tissue damage and loss that is associated with eventual disability.
•  The approved agents decrease the number and severity of relapses, the number and size of new lesions (areas of damage to nerve-insulating myelin), and progression of disability. These treatments work best early in the course of MS, and do not work as well during progressive stages.
• Delaying treatment has been associated with more progression of disability and a larger volume of disease damage as seen on MRI.

The authors conclude that, given that therapies can significantly reduce MS disease activity, then "almost every" patient early in the course of MS should be offered disease-modifying therapy.

On the other hand, Sean J. Pittock, MD, and colleagues (Mayo Clinic, Rochester, MN) cite the reasons for delaying treatment until the course of MS becomes more apparent in an article titled, "Not Every Patient with Multiple Sclerosis Should Be Treated at Time of Diagnosis" (Archives of Neurology 2006;63:611-614):

• If left untreated, MS often runs a "favourable" course, but it becomes difficult to distinguish a favourable course from treatment success if people are treated for a long time.
• The approved treatments are only partially effective in the short-term; it has not been proven that they can prevent long-term disability.
• Drawbacks to treatment include the cost, adverse effects, neutralizing antibodies (immune system proteins that can interfere with the effectiveness of interferons), and some patients' reluctance to make a long-term commitment to taking injected medications.

The authors suggest that monitoring people with MS regularly with clinical examinations and MRI scans may help to identify people whose course requires treatment with disease-modifying therapies. They conclude that well-designed studies are required to determine whether early, versus delayed, treatment of relapsing MS makes a clinically meaningful difference in terms of the development of disability.

In an accompanying editorial, E. S. Roach, MD (Wake Forest University School of Medicine, Winston-Salem, NC) comments on the two reports and concludes in favour of early treatment (Archives of Neurology 2006;63:619).

"One approach, as proposed by Pittock and colleagues, is to defer treatment until the patient's course is better established, possibly allowing those with less aggressive disease to avoid years of unnecessary treatment," comments Dr. Roach. "But as Frohman and colleagues counter, most people with newly diagnosed MS do progress, and we must consider that treatment could be less effective if started later in the course of the illness."

Dr. Roach notes the necessity for finding specific evidence that some people do not need treatment. "Without such evidence for individuals with MS, it will be difficult to know for sure whether it is ever safe to defer treatment," he concludes. "While it would be wonderful if we could avoid treating some patients with MS, until we can distinguish these individuals from the others, it is probably better to offer treatment to all patients except in the setting of a clinical trial."

Source: News-Medical.net ©2006 News-Medical.Net (23/05/06)

While some symptoms remain relatively stable over time in depressed patients with multiple sclerosis (MS), mood symptoms are significantly more variable, according to a study published in the Journal of Neurology, Neurosurgery, and Psychiatry.

"Lifetime prevalence estimates of depression in MS patients are high, typically falling around 50 percent," write Dr. Peter A. Arnett, of Penn State University, University Park, and Dr. John Randolph, of Dartmouth Medical School, Hanover, New Hampshire. Although many studies have looked at a cross section of MS patients with depression, few longitudinal studies have been conducted.

The researchers therefore examined the longitudinal course of and change in clusters of depression symptoms in 53 MS patients. They also assessed the association between interferon beta therapy and the ability of patients to cope with their symptoms of depression. The subjects completed two tests used to evaluate depression -- the Beck Depression Inventory (BDI) and the Chicago Multiscale Depression Inventory (CMDI) - taken at two time points 3 years apart.

Highly significant correlations were observed between time one and time two for BDI scores and most components of the CMDI, and these results changed little over time, according to the authors. However, the component of the CMDI that assessed mood did not correlate well with other components of the CMDI.

The researchers also found that patients who had improvements in their mood used significantly more active coping strategies, whereas those whose mood symptoms worsened used significantly less active coping.

Compared with patients whose depressed mood improved, those whose mood worsened were significantly more likely to be using interferon beta drugs at both time points. Differences in demographic or illness variables did not appear to be related to depressed mood symptoms, according to the authors.

"Nonetheless, it is possible that other variables, not measured as part of this study, contributed more to patients' increased mood disturbance than interferon beta use," the investigators write.

"One possibility is that patients inclined to depressed mood to begin with were more likely to complain about illness related problems and, as such, physicians treating them may have been more likely to prescribe disease-modifying drugs such as interferon beta preparations."

SOURCE: Journal of Neurology, Neurosurgery and Psychiatry, May 2006. (03/05/06)

The Department of Health has sent a reminder to health authorities to fulfil their obligations to MS patients by providing beta interferon and glatirmater acetate (Copaxone) to eligible patients.

The note says they “should be taking steps to prepare for implementation [of prescribing centres], to ensure that prescriptions may be initiated at the earliest opportunity.” It emphasises that “there is a statutory obligation to fund the cost of drugs themselves and any infrastructure costs needed to assess and support patients.”

For further information, refer to the Department of Health.

The Department has now issued a briefing :

Drug treatments for multiple sclerosis (beta-interferons and glatiramer acetate): risk-sharing scheme (HSC 2002/004) briefing note November 2006.

The Risk-Sharing Scheme commenced in May 2002. A cohort of over 5,000 patients with MS is being routinely monitored over 10 years. The purpose of this note is to remind PCTs and Hospital Trusts that there is a statutory duty under directions made under the NHS Act 1977 to fund treatment for eligible patients, including those who are not subject to routine monitoring.

Background

Health Service Circular 2002/004, announcing the risk-sharing scheme, was issued to the NHS on 4 February 2002. The scheme makes provision for MS patients to be eligible for treatment on the NHS with disease modifying drugs. A large cohort of patients is being monitored in order to assess the long-term cost effectiveness of the products. Ministers have expressed their commitment to seeing effective implementation of the scheme. In England this commitment has taken the form of directions under the NHS Act 1977 (see annex D of HSC 2002/004), which place the same statutory funding obligations on NHS bodies as apply to positive recommendations from NICE.

Progress with the Scheme

The Scheme is an observational hypothesis-testing study over 10 years. The study is being conducted as part of routine clinical practice, with data being collected for around 5,200 patients across 70 UK prescribing centres. The recruitment of such a large number of patients represents a considerable achievement. Progress of the disease for patients receiving treatment will be compared with a group of patients who did not receive treatment to gauge the extent to which patients benefit from treatment. Analyses will be conducted on a regular cycle and the first is expected to be completed in summer 2007. The treatments involved are Avonex, Betaferon, Copaxone and Rebif, and if they do not perform as anticipated their prices to the NHS might reduce.

Action for Strategic Health Authorities

Strategic Health Authorities are asked to ensure that their PCTs and Trusts continue to meet their obligations to fund the treatment of eligible patients under the scheme.

Source: Department of Health

© Multiple Sclerosis Resource Centre