Finland: Task Force Report On Pandemrix-Narcolepsy Link

 

 

 

# 5803

 

 

Just over a year ago reports began to come out of Finland suggesting a link between an increase in the rate of narcolepsy among adolescents and GSK’s adjuvanted Pandemrix vaccine.

 

For early coverage of this story, you may wish to revisit Finland Suspends Use of Pandemrix Vaccine and EMA To Review Pandemrix Vaccine, both of which I wrote in August of 2010.

 

Despite some conflicting and incomplete data the European Medicines Agency issued a statement last July recommending:

 

In persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people.

 

 

Note: The use of GSK’s 2009 monovalent Pandemrix vaccine has been largely supplanted by the introduction of last year’s trivalent vaccine, so the impact of this ruling should be minimal.

 

Stockpiles were released last winter in the UK during their surge in flu cases (see UK: To Release Pandemrix Vaccine Stockpile). 

 

The EMA maintained, however, that despite these concerns over the Pandemrix vaccine, the overall benefit-risk remains positive.

 

Since then, we’ve seen a study that linked an increase in narcolepsy to the flu virus itself (see Stanford Study Finds Influenza – Narcolepsy Connection) -  further confusing matters.

 

 

Today, Finland’s National Institute For Health and Welfare Narcolepsy Task Force has released a report where they find an association between the Pandemrix vaccine and increased rates of narcolepsy in children between the ages of 4 and 19.

 

 

Association between Pandemrix and narcolepsy confirmed among Finnish children and adolescents

1 Sep 2011

An association between Pandemrix and narcolepsy among children and adolescents in Finland is confirmed

 

In its final report, the National Narcolepsy Task Force confirms the tentative conclusion published in its Interim Report last January that the Pandemrix vaccine used in the winter of 2009–2010 contributed to the increased incidence of narcolepsy observed among 4–19-year-olds in Finland. According to the report, the increased risk associated with vaccination amounted to six cases of narcolepsy per 100 000 persons vaccinated in the 4–19 age group during the eight months following vaccination. This was 12.7 times the risk of a person in the same age group who had not been vaccinated. No increased incidence of narcolepsy was observed among children under the age of four or among adults over the age of 19.

 

In all the cases examined, narcolepsy associated with Pandemrix vaccination has been identified in persons who carry a genetic risk factor for narcolepsy. Because of this very strong association with the genetic risk factor which regulates immune responses, narcolepsy is considered an immune-mediated disease.

 

In approximately one quarter of those who developed narcolepsy following Pandemrix vaccination, the THL Immunology laboratory found antibodies binding to the AS03 adjuvant component of the vaccine. Adjuvants containing squalene have not previously been reported to induce the production of antibodies. The significance of this preliminary observation will be the subject of further research.

(Continue . . . )

 

 

While more research is needed to nail down exactly what happened, and why, a few key points to ponder.

 

• Of the 3 dozen countries that used the Pandemrix vaccine in 2009-2010, only Finland and Sweden have documented an increase in Narcolepsy that they can link to the Pandemrix vaccine.
• At least a dozen countries reported increased rates of narcolepsy during that time period, including some countries where the vaccine was not used.
• In all the cases the task force examined, narcolepsy associated with Pandemrix vaccination was identified in persons who carry a genetic risk factor for narcolepsy
• Regarding the use of the vaccine, despite the the `unforeseen and deeply regrettable cases of narcolepsy’, Finland’s Narcolepsy taskforce found that its use probably saved lives and that `overall benefit-risk balance remains positive.’
• While unsure of its significance, researchers found antibodies binding to the AS03 adjuvant component of the vaccine in roughly 25% of the cases examined.
• And finally, adjuvanted flu vaccines like Pandemrix were not used in the United States. 

 

Despite rare adverse side effects such as narcolepsy, flu vaccines have an excellent safety profile, and remain our best weapon against a virus that kills tens of thousands every year.

 

Taking any medicine – including a flu vaccine – entails a small degree of risk.  But those risks pale when compared to the risks from catching the flu.

 

And with the potential for seeing an increase in antiviral resistant flu viruses that might limit your treatment options in the future (see Australia Reports Cluster Of Antiviral Resistant H1N1), doing what you can now to protect yourself against infection this winter makes a lot of sense.

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EMA Recommends Interim Measures For Pandemrix Vaccine

 

 

 

# 5494

 

The supposed link between GSK’s Pandemrix Vaccine and an increase in narcolepsy among children and adolescents in a handful of countries has been covered often in this blog over the past 6 months.

 

Today, new we’ve information from the EMA.  But first, a quick review of the story to date.

 

In late August of 2010, shortly after the declared end of the H1N1 pandemic, reports of a possible increase in narcolepsy among children and adolescents who received GSK’s adjuvanted Pandemrix vaccine began to emerge from Finland.

 

On August 25th, I reported Finland Suspends Use of Pandemrix Vaccine, and two days later I blogged on the European Medicines Agency’s plan to review the evidence (see EMA To Review Pandemrix Vaccine).

 

Since then we’ve seen several interim reports that failed to find conclusive evidence of a link between the Pandemrix vaccine and narcolepsy, but which did find reasons to continue the investigation.

 

Sweden: No Link Between Pandemrix And Narcolepsy

EMA Update On The Pandemrix-Narcolepsy Investigation

 

On February 1st, Finland’s National Institute for Health and Welfare released an interim report on what they called a probable link between GSK’s Pandemrix vaccination, and an increase in narcolepsy in children and adolescents 4-19 years of age.

 

Finland: Statement On Pandemrix And Narcolepsy Link

 

A week later, the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) has issued a statement on the potential link between GSK’s Pandemrix vaccine and an increase in rates of narcolepsy among recipients aged 4 to 19.

 

 

While stating that further investigation is warranted concerning narcolepsy and vaccination against influenza (H1N1) 2009 with Pandemrix and other pandemic H1N1 vaccines the advisory group also states that this does not appear to have been a world-wide phenomenon.

 

WHO: GACVS Statement On Narcolepsy And Vaccination

 

Roughly 10 days later, the European Medicines Agency (EMA) released a statement (see EMA: Added Concern, But Insufficient Evidence To Link Vaccine To Narcolepsy) that stated that that its Committee for Medicinal Products for Human Use (CHMP) has reviewed Finnish data on the suspected link between Pandemrix vaccine and an increase in narcolepsy, and has concluded that the new evidence `added to the concern’, but was as yet insufficient to establish a causal relationship.

 

 

Today (April 15th, 2011), in the latest installment in this ongoing investigation, the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Pandemrix’s product information be amended to include concerns over a suspected link to narcolepsy.

 

 

15/04/2011

European Medicines Agency recommends interim measures for Pandemrix

Updated prescribing advice highlights preliminary results from epidemiological studies on narcolepsy; further research needed

 

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the product information for Pandemrix should be amended to advise prescribers to take into account preliminary results from epidemiological studies on Pandemrix and narcolepsy, and to perform an individual benefit-risk assessment when considering the use of Pandemrix in children and adolescents. This is an interim measure pending the outcome of the European review, expected to conclude in July 2011.

 

The CHMP reviewed all available data, including new findings from Sweden and France on the suspected link between narcolepsy in children and adolescents and Pandemrix. The CHMP concluded that, following the earlier results of an epidemiological study from Finland, the new evidence strengthened the signal in children and adolescents, but that the data had methodological limitations. The relationship between Pandemrix and narcolepsy is still under investigation.

 

Preliminary results of the Swedish registry study from October 2009 to December 2010 on Pandemrix vaccination and the risk of narcolepsy indicates a four-fold increase of cases of narcolepsy in children and adolescents (below 20 years of age) who received Pandemrix compared with unvaccinated people of the same age. The additional risk corresponds to an additional 3-4 narcolepsy cases per 100,000 vaccinated subjects. These results are broadly in line with the study results from Finland indicating an association between Pandemrix and narcolepsy in children and adolescents. The study did not identify any increased risk in adults. The CHMP concluded that the study was well conducted, although it has inherent limitations.

 

An analysis of narcolepsy reports in France provides some further evidence.

 

The lack of a clear increase in reports of narcolepsy following Pandemrix in other EU and non-EU countries may point towards the influence of other unknown factors affecting the trend seen in some countries. Also, there is currently no clearly identified biological plausibility for an association between Pandemrix and narcolepsy, and further non-clinical studies, especially in the juvenile setting, are needed.

 

The CHMP considers it important to gather more data on the use of Pandemrix and related vaccines in a variety of countries to further assess this concern. A variety of research efforts are now ongoing. These include an epidemiological study of narcolepsy and pandemic vaccines conducted by the European Centre for Disease Prevention and Control (ECDC) through a network of research and public health institutions (VAESCO) in nine European Union Member States, and an epidemiological study conducted by Glaxo Smith Kline (the marketing authorisation holder of Pandemrix) in Canada. Preliminary results of the VAESCO study and of the Canadian study are expected by July 2011.

 

The CHMP is working with experts from across the EU to assess the possible safety concern and any impact on the benefit-risk balance of Pandemrix. The CHMP plans to hold an expert meeting with participation of international experts, the World Health Organization (WHO) and ECDC.

 

The European Medicines Agency will provide updates as new information becomes available.

(Continue . . . )

 

 

The increase in narcolepsy among children in just a few of the nations that deployed the Pandemrix vaccine remains a medical mystery.   Investigations continue.

 

While some link between the vaccine and the condition may well exist, researchers are looking for a third factor – an unknown catalyst – that may have affected residents of some countries but not others.

 

The Pandemrix vaccine was not used in the United States.

 

This is an evolving story, and for now there are more questions than answers.

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GSK Statement On Pandemrix-Narcolepsy Report

 

 

# 5275

 

 

GlaxoSmithKiline (GSK), the manufacturers of the Pandemrix vaccine which some researchers believe may be linked to an increase in narcolepsy among children aged 4-19 (see Finland: Statement On Pandemrix And Narcolepsy Link), has released a statement of their own today.

 

With other investigations underway, GSK believes it is premature to draw any conclusions on any link between their vaccine and increases in narcolepsy. 

 

I’ve just excerpted a few paragraphs from this press release.  Follow the link below to read it in its entirety.

 

 

Update on Pandemrix™ and interim Finnish report on narcolepsy

Issued: 1 February 2011

GSK is aware of today’s interim report by the Finnish National narcolepsy committee ^[1] on their investigation into reported cases of narcolepsy in Finland. This investigation is independent of a broader ongoing European Medicines Agency (EMA) investigation initiated in 2010. GSK is reviewing the report and believes it would be premature to draw any conclusions on a potential association between Pandemrix and narcolepsy until this European investigation has been completed.

 

Patient safety is of paramount importance to GSK and we have been working closely with the EMA and other national regulatory organisations to better understand the situation since reports of narcolepsy after vaccination with Pandemrix were first received. The company recognises the value of ongoing independent research to add further information.

 

The EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed all of the available data on the suspected link between narcolepsy and Pandemrix in September 2010 and stated at that time that the benefit risk balance for Pandemrix remained positive.  Since then GSK has continued to provide EMA with information on narcolepsy cases being reported to the company and to date there has been no change in EMA’s position.

 

(Continue . . . )

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Sweden: No Link Between Pandemrix And Narcolepsy

 

 

# 4888

 

 

From CIDRAP News tonight, a report by Lisa Schnirring on the findings of Sweden’s Medical Products Agency’s investigation into a possible link between GSK’s Pandemrix vaccine and narcolepsy.

 

The preliminary investigation has found no apparent link between the vaccine and the neurological disorder, as many of the recent cases never received the vaccine. 

 

Follow the link to read the entire report.

 

Sweden finds no link between H1N1 vaccine, narcolepsy

Lisa Schnirring Staff Writer

Sep 9, 2010 (CIDRAP News) – Preliminary results from an investigation by Swedish regulators into reports of narcolepsy in people who received a 2009 H1N1 vaccine found no link between the immunization and the condition.

In a report yesterday from the country's Medical Products Agency, investigators said they found that narcolepsy developed both in people who had and who had not received the vaccine, Finland-based YLE News reported yesterday.

(Continue . . . )

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GSK Press Statement On Pandemrix Investigation

 

 

 

# 4866

 

 

GSK (Glaxo Smith-Kline), manufacturers of the adjuvanted Pandemrix vaccine that has been linked by media reports to a small number of cases of narcolepsy in children – has released a statement today for journalists and investors.

 

 

Reports of narcolepsy in Europe following vaccination with Pandemrix™

WEBWIRE – Friday, September 03, 2010

London UK - GSK initially became aware of possible cases of narcolepsy following vaccination with the adjuvanted H1N1 pandemic vaccine Pandemrix through adverse event reports received by the Swedish Medical Products Agency, and subsequently via media reports in Finland.

 

Information on the individual cases remains limited at present, but GSK is conducting its own investigation in an effort to gather as much additional data as possible regarding the reported cases, and is working closely with key regulatory authorities, including the European Medicines Agency (EMA).

(Continue . . .)

 

 

Although some media reports – particularly those by anti-vaccination activists – have worded stories to suggest that a `probable link’ between the vaccine and these cases of narcolepsy has been established . . .  right now, there is no proof of causation.

 

With further investigation, a link may be established. Flu vaccines have a good safety record, but on rare occasions serious side effects have been noted.

 

That said, the background rates of narcolepsy are poorly understood, and the condition is generally believed to be under-diagnosed.

 

It will take time to know whether the vaccine was responsible for this upsurge in reported cases. 

 

But other possibilities exist.

 

Greater scrutiny, better reporting systems, and the public’s concern over the vaccine’s safety might well account for a greater number of diagnoses of narcolepsy in children over the past 6 months.

 

Essentially, the harder we look for diseases, the more we are likely to find.

 

We’ll simply have to wait to see where these investigations lead.

 

 

 

»» Read More

EMA To Review Pandemrix Vaccine

 

 

# 4840

 

 

The EMA (European Medicines Agency) is a London based EU regulatory agency that is responsible for the scientific evaluation of drugs developed by pharmaceutical companies for use in the European Union. 

 

It is roughly the EU equivalent to the United State’s FDA.

 

Today the EMA announced that they will review GSK’s Pandemrix vaccine to see if they can ascertain any causal link between it - and reports of unusual occurrences of narcolepsy – mostly in children, reported in Sweden and Finland  (see Finland Suspends Use of Pandemrix Vaccine) in recent days.

 

For now, no causal link has been established and the number of reported cases of narcolepsy (which afflicts several thousand  Europeans each year) remains small. 

 

Still, the number of cases among recently vaccinated children has been sufficient to raise concerns, and an investigation will be conducted.

 

 

The EMA press release (h/t Ironorehopper on FluTrackers) provides additional details.

 

 

European Medicines Agency starts review of Pandemrix

The European Medicines Agency has launched a review of Pandemrix on the request of the European Commission to investigate whether there is a link between cases of narcolepsy and vaccination with Pandemrix. A limited number of cases was reported, all collected through spontaneous reporting systems, mainly in Sweden and Finland. Pandemrix, an influenza vaccine, has been used since September 2009 for vaccination against H1N1 influenza in at least 30.8 million Europeans.

 

Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. Its precise cause is unknown, but it is generally considered to be triggered by a combination of genetic and environmental factors, including infections.

 

Although the cases of narcolepsy have been reported in temporal association with the use of Pandemrix, it is at present not known if the vaccine caused the disorder. The Agency’s Committee for Medicinal Products for Human Use (CHMP) will look carefully at all of the available data to determine whether there is evidence for a causal association. As part of this evaluation the Committee will also consider the so-called background rate for narcolepsy, i.e. the number of cases that would normally be expected to be diagnosed.

 

The Committee will be working with experts from across the EU to assess this possible safety concern and any impact on the benefit risk balance of Pandemrix. The Committee will consider at its September 2010 meeting the need for any provisional measures pending completion of the evaluation.

 

The Agency is also liaising with the European Centre for Disease Prevention and Control (ECDC), international regulatory partners and the World Health Organization (WHO).

 

The European Medicines Agency will provide updates as new information becomes available.

Notes:

1. On 24 August 2010, Finland’s National Institute for Health and Welfare recommended that vaccination with Pandemrix be discontinued until the suspected link with narcolepsy is thoroughly evaluated.
2. Pandemrix has been authorised in the European Union since September 2009. The vaccine was extensively used during the 2009 (H1N1) pandemic, with at least 30.8 million Europeans vaccinated.

 

 

 

The Pandemrix vaccine was an adjuvanted monovalent pandemic H1N1 shot, and as such, was not licensed for use in the United States.

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