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PostPosted: Wed Jan 05, 2011 9:29 am    Post subject: PML underdiagnosed in MS patients on Tysabri? Reply with quote

The author of this letter in the Lancet Neurology is affiliated with the Department of Neurology, Rabin Medical Center, Petach Tikva, 49100, Israel

Thanks to Julie Stachowiak who writes the AboutMS blog for calling attention to this letter in the Lancet Neurology (June 2010).
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PostPosted: Tue Jan 18, 2011 6:51 pm    Post subject: (Abstr.) PML under Tysabri--risk stratification... Reply with quote

From PubMed, January 18, 2011:

Quote:
Nervenarzt. 2011 Jan 16.

[Progressive multifocal leukoencephalopathy under natalizumab : Initial possibilities for risk stratification?]

[Article in German]

Warnke C, Adams O, Gold R, Hartung HP, Hohlfeld R, Wiendl H, Kieseier BC.

Neurologische Klinik, Heinrich-Heine-Universität, Moorenstr. 5, 40225, Düsseldorf, Deutschland.

Natalizumab (Tysabri®) is the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS) but while treatment is highly efficient, it carries the risk of progressive multifocal leukoencephalopathy (PML). Based on reports of confirmed cases of PML, the risk of PML might increase beyond 24 months of treatment. Thus, attempts to stratify patients treated with natalizumab into those carrying higher or lower risk for developing PML are currently being undertaken.

Among these strategies JC virus serology might potentially be the first tool available. As a large variety of methods have been published resulting in controversial results for JC virus seroprevalence, standardized testing will be mandatory when applying this method in clinical practice. In addition, risk management strategies for the seropositive majority of patients need to be redefined and optimized further.

PMID: 21240604


The abstract can be seen here.
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PostPosted: Thu Jan 20, 2011 7:02 pm    Post subject: Now 85 PML cases in MS patients on Tysabri Reply with quote

From Dow Jones Newswires, January 20, 2011:

Quote:
Biogen: Six More Cases Of Brain Infection In Tysabri Patients

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Biogen Idec Inc. disclosed six more cases of a rare brain infection in multiple sclerosis patients taking Tysabri, a medication it sells with Elan Corp., bringing the total number of cases to 85 as of Jan. 7.

The Weston, Mass., biotech company reported no new deaths among patients who have developed the infection--known as progressive multifocal leukoencephalopathy, or PML-- so the total stands at 16.

The number of PML cases is important because if the infection rate climbs too high, the drug's sales growth may drop. Regulators recently said that they watch the cases, but have concluded that the benefits of the medicine to MS patients outweigh the risks.

The overall global PML rate is now at 1.06 per 1,000 patients. Although that is above the typical one-in-1,000 rate commonly cited from those trials, Biogen spokeswoman Kate Weiss said the current PML figure falls within that seen in the trials' confidence interval, a statistical tool that helps show the precision of a measurement.

"The numbers are telling us what we already know, that overall risk of PML increases at more than two years, which is what is on the label," said Weiss.
Tysabri is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease. But the rising incidence of the infection has continued to raise concern among some Wall Street analysts as more options for treating the disease are developed.

Tysabri was temporarily withdrawn from the market beginning in 2005 and relaunched in 2006 with a strict access plan that monitors every patient using the drug.

Of the total PML cases, 36 were in the U.S., 44 were in the European Union and five in other areas.
The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months of use. Biogen warns that the drop is inconclusive, because there aren't enough data from patients at the longer duration to have confidence in that finding.

The most recent data translate to a rate of 1.63 cases per 1,000 for patients on the drug for a year or longer, but that rises to 2.13 per 1,000 for those on the drug for two years or longer.
Looked at another way, the rate is about 1.49 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.4 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

The company feels that the latter measure--which has been relatively stable--is the most accurate method of looking at the pool of data because it shows all patients over a fixed duration range of treatment.
There is hope that the development of a blood test may better determine the chances of patients contracting PML. Although the overall risk of the infection remains small, it can have devastating and permanent effects, so the test may make patients and physicians more comfortable with using the drug. Last month, Biogen and Elan proposed updating the label of Tysabri to include information about certain antibodies in the blood being a risk factor for acquiring the infection.

-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com


The article can be seen here.
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PostPosted: Fri Jan 21, 2011 6:59 pm    Post subject: Reply with quote

The chefarztfrau Website has posted some information on the new cases:

#80 - female, Germany, 29 months on Tysabri
#81 - female, USA, 34 doses of Tysabri
#82 - male, Poland, 50 doses of Tysabri
#83 - USA
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PostPosted: Mon Jan 31, 2011 1:21 pm    Post subject: (Abst.) Rare viral infections w/immunosuppressive therapy... Reply with quote

From PeerView Institute, NTK Watch, January 31, 2011 (from PubMed):

Quote:
Z Rheumatol. 2011 Jan 27.

[Rare viral infections during immunosuppressive therapy : A "normal" side effect?]

[Article in German]

Glück T.

Innere Abteilung, Kreisklinik Trostberg, Kliniken Südostbayern, Siegerthöhe 1, 83308, Trostberg, Deutschland, thomas.glueck@kreisklinik-trostberg.de.

The use of biologicals in the therapy of rheumatic diseases allows more effective treatment of patients with very active disease. Such regimens, however, can induce a more severe treatment-related immunosuppression and, as a consequence, opportunistic infections that are rarely seen with conventional immunosuppressive therapy appear to occur more frequently.

The majority of these opportunistic infections are common viral infections which become latent and only cause severe disease if they are reactivated in a severely immunocompromised host. However, some of the newer biologicals, especially natalizumab, efalizumab or rituximab, appear to carry a special risk for the reactivation of JC polyoma virus manifesting as progressive multifocal leukoencephalopathy, a severe, untreatable and often fatal encephalitis. Therefore, such treatments should be used with caution in patients who have been or are being treated with combined immunosuppressive therapy including corticosteroids.

Elderly patients are specifically at risk for this "normal" side effect.

PMID: 21267726


The abstract can be seen here.
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PostPosted: Sun Feb 06, 2011 7:03 pm    Post subject: 10 more PML cases--total now 93, with 19 deaths, up from 16 Reply with quote

The chefarztfrau lists 10 more PML deaths in MS patients on Tysabri. Though most of the entries are based on an "internal source," here they are:

case #84 - Italy, male, 17 months on Tysabri

case #85 - Austria, female, 41 months

case #86 - France, female, 35 months

case #87 - Greece, male, 34 months

case #88 - Greece, male, 35 months

case #89 - Germany, female, 26 months

case #90 - USA, female, 46 doses

case #91 - France, female, 40 months

case #92 - Belgium, male, 38 months

case #93 - USA, female, 20 doses

Two of the cases are in persons who were on Tysabri less than two years.

The deaths are mentioned here. The February 3 entry contains a link to a National MS Society article that is in English.
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PostPosted: Fri Feb 18, 2011 3:24 pm    Post subject: PML cases now total 95, with 20 deaths Reply with quote

Well, Biogen did say some time ago that we could expect to see more PML cases as time passed. Now there have been a total of 95 PML cases with 20 deaths:

http://www.reuters.com/article/2011/02/18/biogen-tysabri-idUSN1811430320110218


According to the chefarztfrau Website, this is what is known about the new cases so far:

#84 - Italy, male, 17 months on Tysabri
#85 - Austria, female, 41 months
#86 - France, female, 35 months
#87 - Greece, male, 34 months
#88 - Greece, male, 35 months
#89 - Germany, female, 26 months
#90 - USA, female, 46 doses
#91 - France, female, 40 months
#92 - Belgium, male, 38 months
#93 - USA, female, 20 doses
#94 - not known
#95 - not known
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PostPosted: Tue Mar 15, 2011 6:36 pm    Post subject: (Article) Biogen halts enrollment in Tysabri trial... Reply with quote

From Capital.gr, March 15, 2011 (this is a news release from Dow Jones as it appeared on a Greek financial Website):


Quote:
Biogen Halts Enrollment In Tysabri Trial, Citing Slow Pace

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Biogen Idec Inc. (BIIB) has halted enrollment in a large, long-term clinical trial aimed at testing the earlier use of multiple sclerosis drug Tysabri, citing a slower-than-expected pace of finding participants.

The Surpass study aims to test the effectiveness of Tysabri, sold with Elan Corp. (ELN), when patients switched from more widely used drugs. Tysabri has proved to be highly effective; however, because of a link to a rare brain infection, the patients taking the drug tend to be those who have stopped responding to other drugs or have aggressive cases of MS.

The study started a year ago and had aimed to enroll 1,800 patients to be followed for about two years, yielding data in 2013 or 2014. Enrollment was stopped last month, but participating patients will continue in the trial.

Biogen spokeswoman Kate Weiss declined to comment on the number of patients enrolled, citing policy. The company has decided to devote its resources toward "risk stratification" efforts for the drug and remains dedicated to studying its effectiveness, she said.

Tysabri has been linked in a small number of patients to a serious brain infection called progressive multifocal leukoencephalopathy, or PML. Global sales rose 16% to $1.2 billion last year, although growth has been lower than originally expected in recent years because of the risks of the infection.

Biogen is developing a blood test that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.

The Surpass trial was designed to measure Tysabri's effectiveness in patients with active MS that have switched from either Teva Pharmaceutical Industries Ltd.'s (TEVA) Copaxone or Rebif, sold by Pfizer Inc. (PFE) and Germany's Merck KGaA (MRK.XE, MKGAY).

The goal of the Surpass trial is to get physicians to use Tysabri when patients aren't responding to their current therapy, rather than switching them to more mainstream therapies and using Tysabri as a last resort.

But the design of the trial meant that patients weren't assured that they would switch treatments at all, something that proved to be a hurdle, Weiss said.

The difficulty comes as many new MS treatments are in development, and Novartis AG (NVS) recently launched Gilenya, the first oral treatment for the condition.

"The MS environment is changing and we need to adapt to that change," Weiss said. "This made it challenging to enroll in light of the current clinical trial landscape and the trial itself."


-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com




_________________
MS diagnosed 1980.

Avonex 2002-2005. Copaxone 2007-2010.


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PostPosted: Fri Mar 18, 2011 6:41 pm    Post subject: 7 more PML cases, 1 new death Reply with quote

From NASDAQ, March 18, 2011:



Quote:


Biogen Reports 7 More Infections In Tysabri Patients



By Thomas Gryta

Of DOW JONES NEWSWIRES



NEW YORK -(Dow Jones)- Biogen Idec Inc. reported seven more cases of a rare brain infection among multiple-sclerosis patients taking Tysabri, sold with Elan Corp. , bringing the total number of affected patients to 102 as of March 4.



The Weston, Mass., biotech company reported that one more of those patients has died, bringing total deaths to 21. The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.



The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease.

Biogen recently halted enrollment in a major clinical trial aimed at testing the earlier use of Tysabri, citing a slower-than-expected pace of finding participants and the desire to devote resources toward "risk stratification" efforts for the drug.



Biogen is developing a blood test that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.



Regulators have said that they monitor cases of PML as they occur and have concluded that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that monitors patients.



The overall global PML rate is now at 1.23 per 1,000 patients. A Biogen spokeswoman said the current PML figure is "still generally within what we saw in clinical trials."



Of the total PML cases, 42 were in the U.S., 55 were in the European Union and five in other areas.

The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months. Biogen is studying this drop and warns there is limited information from patients on the drug longer than 36 months.



The most-recent data translate to a rate of 1.87 cases per 1,000 patients on the drug for a year or longer, rising to 2.41 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years.



Looked at another way, the rate is about 1.68 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.44 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.



-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com



The article can be seen here.



According to the chefarztfrau Website, which documents the cases as they occur based on information from "internal sources," what is known about the new cases is:



#96 - USA - female - 22 doses of Tysabri



#97 - Luxembourg - female - 35 months on Tysabri



#98 - Italy - female - 33 months



#99 - USA - male - 51 doses



#100 - USA - female - 22 doses



#101 - USA - female - 34 doses



#102 - Hungary - female - 37 doses
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PostPosted: Wed Apr 20, 2011 10:37 pm    Post subject: 9 more PML cases--total now 111 w/22 deaths Reply with quote

I can't bring myself to include the last sentence in this article when I post it on a larger board.

From the Wall Street Journal, April 20, 2011:

Quote:
Biogen: Nine New Cases Of Brain Infections In Tysabri Patients

By Thomas Gryta
Of DOW JONES NEWSWIRES

NEW YORK (Dow Jones)--Biogen Idec Inc. (BIIB) reported nine more cases of a rare brain infection among multiple-sclerosis patients taking Tysabri, sold with Elan Corp. (ELN, ELN.DB), bringing the number of affected patients to 111 as of April 1.

The Weston, Mass., biotech company reported that one more of those patients has died, bringing total deaths to 22. The cases of the infection--known as progressive multifocal leukoencephalopathy, or PML--are closely watched as the MS market becomes increasingly competitive.

The drug is generally regarded as highly effective, but mostly used for patients that have stopped responding to other drugs or have aggressive cases of the disease.

Biogen is developing a blood test to test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML. The test recently received CE Mark approval in Europe and the companies are conducting large studies of its effectiveness.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

European regulators recently recommended the label include language indicating that JC virus antibody status is a PML risk factor. In the U.S., Biogen and Elan have proposed making a similar change.

Also recently, the U.S. label was updated to include the updated incidence of PML.

Regulators monitor cases of PML as they occur and have said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that monitors patients.

The overall global PML rate is now at 1.31 per 1,000 patients. Of the total PML cases, 46 were in the U.S., 59 were in the European Union and six in other areas.

The risk of the infection generally increases with the number of monthly infusions that a patient receives, but that rate appears to drop after 30 months. Biogen is studying this drop and has warned there is limited information from patients on the drug longer than 36 months.

The most-recent data translate to a rate of 1.99 cases per 1,000 patients on the drug for a year or longer, rising to 2.5 per 1,000 for those on the drug for two years or longer, and dropping to 1.4 for more than three years.

Looked at another way, the rate is about 1.74 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.48 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

Biogen shares were unchanged after hours.

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PostPosted: Thu Apr 21, 2011 6:00 pm    Post subject: More information about the 9 new cases Reply with quote

The chefarztfrau Website has posted some information about the 9 new PML cases.

Case #102 is a female in Hungary, who had 37 doses of Tysabri.

Cases 103, 104, 105, and 106 are in the USA. No additional information yet.

Still no information about cases 107-111.


Last edited by agate on Wed Dec 07, 2011 5:40 pm; edited 1 time in total
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PostPosted: Sat Apr 30, 2011 4:51 pm    Post subject: Reply with quote

The revised FDA drug safety guidelines for Tysabri can be seen here.
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PostPosted: Tue May 03, 2011 6:26 pm    Post subject: Apparently 10 new PML cases--total now 121 Reply with quote

I don't have any other references for this but the chefarztfrau Website is now listing a total of 121 PML cases among MS patients on Tysabri.

Details about cases 107-121 are as follows:

#107 - USA, female, 52 doses
#108 - USA, male, 31 doses
#109 - Switzerland, female, 49 doses
#110 - Spain, female, 42 doses
#111 - USA, female, 55 doses
#112 - Germany, male, 52 doses
#113 - Germany, male, 42 doses
#114 - Iceland, female, 53 doses
#115 - USA, female, 45 doses
#116 - USA, male, 30 doses
#117 - Portugal, female, 50 doses
#118 - USA, male, 30 doses
#119 - Netherlands, male, 44 doses
#120 - Spain, female, 51 doses
#121 - Germany, female, 48 doses
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PostPosted: Thu May 12, 2011 6:39 pm    Post subject: New data at AAN conference alter safety considerations Reply with quote

Internal Medicine News, May 12, 2011, has an interesting article about safety considerations with Tysabri. The article can be seen here.

lady_express_44, please note that the Dr. John Foley you mentioned is quoted in this article though not on the topic you were looking for. He's with the Rocky Mountain MS Clinic in Salt Lake City, according to the article.
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PostPosted: Wed May 18, 2011 6:43 pm    Post subject: (Abstr.) Clinical outcomes of Tysabri-related PML Reply with quote

From PubMed, May 18, 2011:

Quote:
Neurology. 2011 May 17;76(20):1697-704.

Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy.

Vermersch P, Kappos L, Gold R, Foley JF, Olsson T, Cadavid D, Bozic C, Richman S.

Source

Biogen Idec, Inc., 14 Cambridge Center, Cambridge, MA 02142 sandra.richman@biogenidec.com.

OBJECTIVE:

Natalizumab, a therapy for multiple sclerosis (MS), has been associated with progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the CNS associated with the JC virus. We assessed clinical outcomes and identified variables associated with survival in 35 patients with natalizumab-associated PML.

METHODS:

Physicians provided Karnofsky scores and narrative descriptions of clinical status. Data were supplemented by the natalizumab global safety database.

RESULTS:

At the time of analysis, 25 patients (71%) had survived. Survivors were younger (median 40 vs 54 years) and had lower pre-PML Expanded Disability Status Scale scores (median 3.5 vs 5.5) and a shorter time from symptom onset to diagnosis (mean 44 vs 63 days) compared with individuals with fatal cases.

Of patients with nonfatal cases, 86% had unilobar or multilobar disease on brain MRI at diagnosis, whereas 70% of those with fatal cases had widespread disease. Gender, MS duration, natalizumab exposure, prior immunosuppressant use, and CSF JC viral load at diagnosis were comparable.

Most patients were treated with rapid removal of natalizumab from the circulation. The majority of patients developed immune reconstitution inflammatory syndrome and were treated with corticosteroids. Among survivors with at least 6 months follow-up, disability levels were evenly distributed among mild, moderate, and severe, based on physician-reported Karnofsky scores.

CONCLUSIONS:

Natalizumab-associated PML has improved survival compared with PML in other populations. Disability in survivors ranged from mild to severe. A shorter time from symptom onset to diagnosis and localized disease on MRI at diagnosis were associated with improved survival. These data suggest that earlier diagnosis through enhanced clinical vigilance and aggressive management may improve outcomes.

PMID:21576685


The abstract can be seen here.
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PostPosted: Thu May 19, 2011 9:25 pm    Post subject: Now 124 PML cases Reply with quote

From NASDAQ.com, May 19, 2011:

Quote:
Biogen: 13 More Cases Of Brain Infection In Tysabri Patients

By Thomas Gryta, Of DOW JONES NEWSWIRES

NEW YORK -(Dow Jones)- Biogen Idec Inc. reported 13 more cases of a rare brain infection occurring in multiple-sclerosis patients taking the drug Tysabri, sold with Elan Corp., bringing the affected patients to 124 as of May 4.

The Weston, Mass., biotech company said there was one more death among those patients, bringing total deaths to 23. The incidence of the infection-- progressive multifocal leukoencephalopathy, or PML--is updated monthly and is closely watched.

Tysabri is seen as a highly effective medicine for the debilitating condition, but it is mostly used for patients that have stopped responding to other MS drugs or have particularly aggressive cases.

Biogen is developing a blood test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML. The test received CE Mark approval in Europe earlier this year and the companies are conducting large studies of its effectiveness.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

European regulators recently recommended Tysabri's label include language indicating that JC virus antibody status is a PML risk factor. In the U.S., Biogen and Elan have proposed making a similar change. The U.S. label was updated last month to include the updated incidence of PML.

Regulators monitor cases of PML as they occur and have said that the benefits of the medicine outweigh the risks. Tysabri was withdrawn from the market in 2005 and relaunched in 2006--because of its effectiveness--with a strict access plan that regularly monitors patients.

The overall global PML rate is now at 1.44 per 1,000 patients. Of the total PML cases, 49 were in the U.S., 69 were in the European Union and six in other areas.

The risk of the infection generally increases with the number of monthly intravenous infusions that a patient receives, but that rate drops after 30 months. Biogen is studying this apparent decrease, warning that there is limited information from patients on the drug longer than 36 months.
The most-recent data translate to a rate of 2.18 cases per 1,000 patients on the drug for a year or longer, rising to 2.76 per 1,000 for those on the drug for two years or longer, and dropping to 1.6 for more than three years.

Looked at another way, the rate is about 1.89 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.49 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

Biogen shares recently traded down 36 cents, to $97.40, while American Depositary Shares of Elan fell 7 cents, to $8.66.
-By Thomas Gryta, Dow Jones Newswires; 212-416-2169; thomas.gryta@dowjones.com


No details yet about the 3 additional cases.

The article can be seen here.
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PostPosted: Sat May 28, 2011 7:06 pm    Post subject: Indolent course of PML during Tysabri treatment in MS Reply with quote

At last, some information on one of the PML cases. I don't have the original article by Vennegoor et al., though.

From Neurology, May 25, 2011:

Quote:
Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in MS

Michael Y. Ko, Assistant ProfessorDusan Stefoski, Roumen Balabanov
1653 Rush University Medical Ctr, W. Congress Parkway, Chicago, Illinois 60612

Vennegoor et al. reported MRI abnormalities 4 months prior to the onset of clinical symptoms for progressive multifocal leukoencephalopathy (PML). [1] We also treated a similar natalizumab-associated PML multiple sclerosis (MS) patient with an 18-month course of progressive left lower extremity weakness before PML was confirmed.

At onset and during the subsequent 12 months, repeated brain and spine MRIs did not reveal any new or changing lesions from baseline. At one year, the MRI demonstrated a significant enlargement of a previously known right precentral gyrus demyelinating lesion. PML was suspected, but CSF JC virus (JCV) viral load—assays for 50 or greater copies—was negative. However, the suspicion of PML persisted and natalizumab was discontinued after 14 months after the onset of symptoms.

Throughout our patient’s course, the weakness progressed despite several rounds of IV corticosteroids. After 18 months, the brain MRI revealed further enlargement of the gyral lesion and two new non-enhancing lesions suggestive of PML. Repeat CSF JCV viral PCR [polymerase chain reaction] was positive. After receiving the published empiric therapy for PML and corticosteroids for immune reconstitution inflammatory syndrome, the patient improved and later returned to work. [2] PML can present with a protracted clinical course as seen in our patient. However, unlike Vennegoor et al.'s case, our patient had unchanged brain MRIs and a negative CSF JCV PCR even as symptoms progressed. We detected MRI abnormalities after the PML spread into the local white matter but conventional MRIs may not easily detect cortical PML lesions. [3]

Additionally, the protracted clinical course could have caused a slower rise in CSF JCV viral load, which is more difficult to detect by PCR. The sensitivity of diagnosing PML could be increased with serial PCR testing as the JCV viral load increases with disease progression. [4] Even with negative studies, PML was further suspected because IV corticosteroids did not improve the symptoms. In addition, the initial lesion enlarged.

We believe that natalizumab did not accelerate the progression of symptoms or time to confirm PML in our patient although 14 natalizumab infusions were given after symptoms appeared. Natalizumab may have initiated PML without altering its course.

References
1.Vennegoor A, Wattjes MP, van Munster ETL, et al. Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in MS. Neurol 2011;76:574-576.

2. Clifford D, DeLuca A, Simpson DM, et al. Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases. Lancet Neurol 2010;9:438-446.

3. De Toffol B, Vidailhet M, Gray F, et al. Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI. Neurol 1994;44:2352-2355.

4.Landry ML, Eid T, Bannykh S, Majors E. Case report. False negative PCR despite high levels of JC virus DNA in spinal fluid: Implications on diagnostic testing. J Clin Vir 2008;43:246-249.

Disclosures:

Dr. Michael Ko received consulting fees from Biogen Idec and serves on the speakers’ bureau for Biogen Idec, EMD Serono, and Pfizer. Dr. Stefoski serves on the speakers’ bureau of and received consulting fees from Biogen Idec, Accorda, Teva Pharmaceutical and Novartis; receives royalties from Accord; listed as a co-inventor in a patent application describing the utility of cell free plasma DNA in biomarker development. Dr. Balabanov received consulting fees from Biogen Idec, Teva Pharmaceutical, and Novartis; receives research support from the National Institute of Health and the National Multiple Sclerosis Society; is a co-inventor in a patent application describing the utility of cell free plasma DNA in biomarker development.


Reply from the authors:

Quote:
A. Vennegoor, MS Center AmsterdamM.P. Wattjes, E.T.L. van Munster, J. Killestein, and C.H.
MS Center Amsterdam, the Netherlands

We thank Ko et al. for their interest in our article and sharing their experience with PML in a natalizumab-treated relapsing-remitting MS patient.

Their case underlines that the course of PML can be clinically and radiologically protracted despite continuing natalizumab treatment. It confirms our message that clinical and radiological vigilance is vital.



The article and the letter can be seen here.
_________________
MS diagnosed 1980.

Avonex 2002-2005. Copaxone 2007-2010.


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PostPosted: Tue Jun 07, 2011 6:35 pm    Post subject: Update shows higher incidence of Tysabri-associated PML Reply with quote

From Medscape Medical News from the CMSC (Consortium of Multiple Sclerosis Centers) annual meeting, June 7, 2011:

Quote:
Update Shows Higher Incidence of Natalizumab-Associated PML

Kate Johnson


June 7, 2011 (Montreal, Quebec) — Numbers are higher than previously reported for the postmarketing incidence of progressive multifocal leukoencephalopathy (PML) associated with the use of natalizumab (Tysabri, Biogen Idec), according to an update presented here at the Consortium of Multiple Sclerosis Centers 25th Annual Meeting.

As of May 2011, there have been 124 reported cases of natalizumab-associated PML worldwide among 83,300 patients treated for multiple sclerosis (MS), said John Foley, MD, from Rocky Mountain Multiple Sclerosis Clinic, in Salt Lake City, Utah, and a consultant for the company.

That is an overall incidence of 1.4 cases per 1000 patients — an increase from the 1.2 per 1000 rate announced by the US Food and Drug Administration (FDA) and reported by Medscape Medical News in April.

Rare Opportunistic Infection

Natalizumab was first approved by the FDA in 2004 to treat relapsing forms of MS but was temporarily withdrawn from the market the following year because of its association with PML — a rare opportunistic infection of the central nervous system infection caused by the John Cunningham virus (JCV).

The drug was reintroduced in 2006 with stricter safety warnings and monitoring recommendations, and this spring, labeling was updated to quantify postmarketing PML incidence rates according to duration of exposure.

Now, a further update presented at this meeting shows the highest PML incidence continues to be in patients who have received 2 to 3 years of monthly natalizumab infusions — in whom there is a current PML rate of 1.89 cases per 1000 patients, up from the previously reported 1.5 cases, reported Dr. Foley.

In contrast, patients who have received between 3 and 4 years of infusions continue to have a lower incidence, at 1.10 cases per 1000 — up from 0.9 cases.

"We're, of course, very interested in what's happening here," commented Dr. Foley. "Is this real or a statistical artefact? We still have small numbers of patients out in this range."

Finally, the lowest PML rates continue to be in patients who have received 2 years or less of monthly infusions, in whom the most recent incidence is 0.49 cases per 1000 patients — up from 0.3 cases, he said.

"Clearly, the statistics are suggesting that the longer you're on the drug, the higher the risk. It also looks like there's a more definitive association being established with prior immunosuppressant therapy. And, we now have, probably what you might call a secondary risk stratification factor — that being the JCV antibody — [for which a screening test] is currently completing its experimental phase and will likely move into a commercial phase most likely this year."

JCV Antibody

According to company data, all cases of PML in which anti-JCV antibody status had been determined at least 6 months before symptom onset have been antibody positive, said Dr Foley.

In a subset of 79 such cases (median follow-up, 9.3 months from symptom onset), prior exposure to immunosuppressant therapy and longer duration of natalizumab exposure also appeared to confer a greater risk.

Among patients with anti-JCV antibody positivity and up to 2 years of monthly infusions, the incidence of PML was 0.35 cases per 1000 in those without prior immunosuppressant exposure, compared with 1.2 cases per 1000 in those with prior immunosuppressant exposure.

Similarly, among antibody-positive patients with up to 4 years of monthly infusions, the incidence of PML was 2.5 cases per 1000 among those without prior immunosuppressant exposure and 7.8 cases per 1000 in those with prior immunosuppressant exposure.

"Obviously, this is of significant concern, and I think the majority of practitioners are moving to rearrange this [latter] category as far as therapeutics," he said.

Among the 79 cases there has been a 20% mortality rate, "which is significantly lower than in the HIV population and might suggest that patients with normally functioning immune systems do better with PML," noted Dr. Foley. The median time from diagnosis to death was approximately 2 months.

However, among those patients who have survived with at least 6 months of follow-up, most (87%) rate moderate to severe on the Karnofsky Performance Status Scale.

"Usually, patients look fairly encephalopathic, there are changes in behavior and personality, there's often times motor paresis, usually hemiparesis, language disturbance is very common, and visual field defects are very common. [Magnetic resonance imaging] usually shows nonenhancing T2 lesions...and usually the JCV DNA cell counts are fairly low — reemphasizing the fact that a high-sensitivity assay really needs to be done if there's a suspicion of the disease," he said.

Despite treatment with either plasma exchange or immunoadsorption, "the vast majority" of patients developed immune reconstitution inflammatory syndrome usually by 4 weeks after diagnosis, he added.

PML survival appears to be associated with rapid diagnosis and treatment, as well as younger age — with the average age of patients with fatal cases being 52 years compared with 43 years in the patients with nonfatal cases, he reported.

In addition, localized unilobar disease had the lowest mortality rate (12.5%) compared with multilobar disease (25%), with widespread disease carrying a 63% mortality rate.

"Clearly, clinical vigilance is very important — we have hope that the JC antibody will help us as a stratification measure, and we continue to look at and hopefully define some further secondary and tertiary risk stratification measures to better manage natalizumab in this patient population," said Dr. Foley.

No Cause for Complacency

Although JCV antibody status appears to be associated with PML risk, it is premature to rely too heavily on it, based on retrospective data, warned Mark S. Freedman, MD, professor and director of multiple sclerosis research at the University of Ottawa, in Ontario, Canada.

"They have yet to find someone who had PML that did not have antibody positivity — but not everyone who had PML had an antibody test done," he explained to Medscape Medical News.

"The big question is, if you're antibody negative does that assure you 100% safety? The retrospective data suggest this might be true — but now they need to look prospectively. What I'm against is people saying it's a 'fait accompli' that if this test is negative you have no risk. Based on retrospective data, you probably have a lower risk, but is it zero? How high is that risk? We don't know."

In addition, although the data show an 80% survival rate, this comes at a price, he said. "This is a miserable disease. If you got it, you'd probably rather be dead because there's no treatment for it — it destroys brain tissue. Eighty percent to 90% of people are highly disabled if they survive PML."

And although the latest figures suggest a slight downturn in incidence after 3 years of treatment duration, Dr. Freedman says this is no cause for complacency.

"I think the fall-off was really that people started getting cold feet about leaving people on it for 3 or 4 years, so the incidence went down because they took patients off it," he said. "Now it's going back up because they were all reassured. We've now got the data from 48 to 72 months and it's back up again."

_____________________________

Dr. Foley declared consulting fees from Biogen Idec, Genzyme, and Teva and honoraria from Biogen Idec and Teva. Several of the study's coauthors are Biogen Idec employees. Dr. Freedman declared consulting fees from Biogen Idec, Bayer HealthCare, Celgene, Sanofi-Aventis, Novartis, Merck Serono, and Genzyme. Dr. Freedman is also an uncompensated member of the editorial advisory board for Medscape.

Consortium of Multiple Sclerosis Centers (CMSC) 25th Annual Meeting: Abstract P15. Presented June 2, 2011.


Authors and Disclosures

Journalist Kate Johnson
Freelance writer, Montreal, Canada



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PostPosted: Wed Jun 15, 2011 10:31 am    Post subject: (Abstr.) Tysabri & drug holiday in very active RRMS... Reply with quote

From PubMed, June 15, 2011:

Quote:
J Neurol Sci. 2011 Jun 10.

Natalizumab and drug holiday in clinical practice: An observational study in very active relapsing remitting multiple sclerosis patients.

Kerbrat A, Le Page E, Leray E, Anani T, Coustans M, Desormeaux C, Guiziou C, Kassiotis P, Lallement F, Laplaud D, Diraison P, Rouhart F, Sartori E, Wardi R, Wiertlewski S, Edan G.

Source

Service de neurologie, CIC-P 0203 INSERM ,centre hospitalier universitaire, Rennes, France.

BACKGROUND:

In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed.

OBJECTIVE:

The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting multiple sclerosis (RRMS) patients.

METHODS:

In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab.

RESULTS:

A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI.

CONCLUSION:

Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.



The abstract can be seen here.
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PostPosted: Thu Jun 16, 2011 6:25 pm    Post subject: 9 new PML cases Reply with quote

Not much information yet except that 9 new cases of PML have been posted on the chefarztfrau Website, bringing the total to 133.

Case #133 (6/1/11) is in the USA, but that is all of the additional information so far.
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PostPosted: Sun Jun 19, 2011 1:41 pm    Post subject: One new PML death--total now 24 Reply with quote

The chefarztfrau Website lists one new PML death of an MS patient on Tysbri, bringing the total to 24. cussing
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PostPosted: Fri Jul 15, 2011 4:06 pm    Post subject: 12 new PML cases--total now 145, with 5 new deaths Reply with quote

Sad sad news. From MarketWatch, July 15, 2011:

Quote:
12 cases of brain infection in Tysabri patients

By Thomas Gryta

--Biogen reports 12 more cases of infection, brings total to 145

--Five more patients die, bringing total to 29

--Company provides updated data on diagnostic test efforts

NEW YORK -(MarketWatch)- Biogen Idec Inc. (NASDAQ:BIIB) reported 12 more cases of a rare brain infection occurring in multiple-sclerosis patients taking the drug Tysabri, sold with Elan Corp. (ELN, ELN.DB), bringing the affected patients to 145 as of July 5.

The Weston, Mass., biotech company said there was five more deaths among those patients, bringing total deaths to 29, and provided updated data on its effort to develop a risk-assessment test for the infection. The incidence of the infection -- progressive multifocal leukoencephalopathy, or PML -- is updated monthly and is closely watched.

The drug is considered to be highly effective, but it is mostly reserved for patients that stop responding to other MS drugs or have an aggressive case of the debilitating disease.

Biogen is developing a blood test for antibodies to a specific virus, JC virus, something that may better determine the chances of patients contracting PML.

Many people carry JC virus and it causes no harm, but some biologic drugs that modulate the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

Biogen reported that one patient diagnosed with PML among the latest data actually tested negative for the JCV antibody at the time of diagnosis. The company said the outcome was likely because the test was given after use of plasma-exchange therapy, a process that removes large molecules from the body's blood that accelerates removal of Tysabri and theoretically improving the immune response to PML infection.

The company doesn't know why the patient's physician used the test in that way, a spokeswoman said.

The process of testing newly diagnosed patients -- who by definition should be positive with the JCV antibodies -- is a way of testing the effectiveness of the diagnostic tool. Of those tested, 46 out of 47 were positive at diagnosis.

Among patients with JCV antibody status data from prior to diagnosis with PML, 30 patients that developed the infection previously had the JCV antibodies.

Regulators monitor cases of PML as they occur and have repeatedly said that the benefits of the medicine outweigh the risks. ...

The overall global PML rate is now at 1.62 per 1,000 patients. Of the total PML cases, 57 were in the U.S., 81 were in the European Union and seven were in other areas.

The company believes that the best way to assess the pool of PML data shows all patients over a fixed duration range of treatment.

According to that method, the rate is about 1.94 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.54 case per 1,000 patients in those using it for one to two years, and it is essentially nonexistent in patients using it for less than a year.

For patients on the drug for three to four years, the rate drops to 1.34 patients per 1,000, but Biogen doesn't believe there is enough data to conclude that incidence of the infection drops after a certain amount of time.

Looked at another way, the rate is 2.41 cases per 1,000 patients on the drug for a year or longer, rising to 3.03 per 1,000 for those on the drug for two years or longer, and dropping to 1.85 for more than three years.

Biogen shares recently traded down up 1% to $104.30, while American Depositary Shares of Elan fell 0.9% to $11.98.


The article can be seen here.

According to the chefarztfrau Website, 7 of the new cases are in the US. No location is given yet for the others.
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PostPosted: Fri Aug 19, 2011 7:44 am    Post subject: 5 new PML cases in MS patients on Tysabri--total now 150 Reply with quote

The chefarztfrau Website has listed 5 new PML cases, bringing the total to 150. One of the new cases is in the US, but the location of the others isn't given.

http://chefarztfrau.de/?page_id=716
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PostPosted: Tue Sep 06, 2011 6:02 pm    Post subject: 7 new PML cases--total now 157 Reply with quote

The total number of Tysabri-related PML cases has increased by 7 since the last listing. There have now been 157 cases.

Sorry but there's no more information about the cases just now.

http://chefarztfrau.de/?page_id=716
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PostPosted: Fri Sep 09, 2011 7:01 am    Post subject: Reply with quote

Notice how they aren't giving out ANY information now?
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PostPosted: Fri Sep 09, 2011 8:16 am    Post subject: Reply with quote

Yes indeed I have noticed. They're doing a great job of keeping it under wraps, I'd say.

For a while there'd be a few items in the financial sources though they'd come along much later than the chefarztfrau listings. Now there are only the chefarztfrau listings.
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PostPosted: Mon Sep 19, 2011 10:40 am    Post subject: 159 PML cases now, both in the US Reply with quote

The unofficial tabulation for Tysabri-related PML cases has changed from 157 to 159 cases. Both of the new cases are in the US.
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PostPosted: Wed Sep 28, 2011 7:37 pm    Post subject: National MS Society update states 159 PML cases Reply with quote

According to an update of the National MS Society's Webpage on Tysabri-related PML cases, as of September 21 there have been 159 PML cases. The page can be seen here.
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PostPosted: Fri Oct 07, 2011 9:08 am    Post subject: Cochrane Database: Tysabri for RRMS Reply with quote

Note the last sentence in the abstract.

From PubMed, October 7, 2011:

Quote:
Cochrane Database Syst Rev. 2011 Oct 5;10:CD007621.

Natalizumab for relapsing remitting multiple sclerosis

Pucci E, Giuliani G, Solari A, Simi S, Minozzi S, Di Pietrantonj C, Galea I.

U.O. Neurologia - Ospedale di Macerata, ASUR Marche - Zona Territoriale 9, Via Santa Lucia, 3, Macerata, Italy, 62100.

BACKGROUND:

Natalizumab (NTZ) (Tysabri(®)) is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier, thus reducing inflammation in central nervous system, and has been approved worldwide for the treatment of relapsing-remitting multiple sclerosis (RRMS).

OBJECTIVES:

To evaluate the efficacy, tolerability and safety of NTZ in the treatment of patients with RRMS.

SEARCH STRATEGY:

We searched the Cochrane Multiple Sclerosis Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2010, Issue 1), MEDLINE (PubMed) and EMBASE, all up to 19 February 2010, and bibliographies of papers. Handsearching was carried out. Trialists and pharmaceutical companies were contacted. Furthermore, the websites of US Food and Drug Administration (FDA), the European Medicines Evaluation Agency (EMA) and the National Institute for health and Clinical Excellence (NICE) were also checked.

SELECTION CRITERIA:

All double-blind, randomised, controlled trials analysing more than a single infusion of NTZ (dosage > 3 mg/kg intravenous infusion every 4 weeks), also including its use as add-on treatment, versus placebo or other drugs in patients with RRMS. No restrictions on the basis of duration of treatment or length of follow up.

DATA COLLECTION AND ANALYSIS:

Three reviewers independently selected articles which met the inclusion criteria. Disagreements were solved by discussion. Two reviewers independently extracted the data and assessed the methodological quality of each trial. Missing data was sought by contacting principal authors and Biogen Idec, through Biogen-Dompé Italia.

MAIN RESULTS:

Three studies met the inclusion criteria. These included one placebo-controlled trial (942 patients) and two add-on placebo-controlled trials, i.e. one plus glatiramer acetate (110 patients) and the second plus interferon beta-1a (1171 patients).This review assessed the efficacy, tolerability and safety of NTZ in patients with RRMS.

Data was conclusive with respect to efficacy and tolerability, but not safety. As far as efficacy is concerned, the results showed statistically significant evidence in favour of NTZ for all the primary outcomes and for the secondary ones where data was available. NTZ reduced the risk of experiencing at least one new exacerbation at 2 years by about 40% and of experiencing progression at 2 years by about 25% as compared to a control group. MRI parameters showed statistical evidence in favour of participants receiving NTZ. Infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginitis and menstrual disorders were reported as adverse events (AEs) more frequently after NTZ treatment. In this review NTZ was found to be well tolerated over a follow-up period of two years: the number of patients experiencing at least one AE (including severe and serious AEs) during this period did not differ between NTZ-treated patients and controls. Safety concerns have been raised about Progressive Multifocal Leukoencephalopathy (PML). In the trials included in this review, two cases of PML were encountered: one in a patient who had received 29 doses of NTZ and a second fatal case of PML in another patient after 37 doses of NTZ. Our protocol was insufficient to evaluate PML risk as well as other rare and long-term adverse events such as cancers and other opportunistic infections, which are very important issues in considering the risk/benefit ratio of NTZ.

AUTHORS' CONCLUSIONS:

Although one trial did not contribute to efficacy results due to its duration, we found robust evidence in favour of a reduction in relapses and disability at 2 years in RRMS patients treated with NTZ. The drug was well tolerated. There are current significant safety concerns due to reporting of an increasing number of PML cases in patients treated with NTZ. This review was unable to provide an up-to-date systematic assessment of the risk due to the maximum 2 year-duration of the trials included. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs.

All the data in this review came from trials supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias.



The abstract can be seen here.
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PostPosted: Fri Oct 14, 2011 7:58 am    Post subject: 11 more PML cases Reply with quote

The unofficial chefarztfrau Website is listing 11 new Tysabri cases, bringing the total to 170:

http://chefarztfrau.de/?page_id=716.

Of the new cases, 4 are in the US.
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PostPosted: Sat Nov 19, 2011 10:17 am    Post subject: Reply with quote

Total PML cases in MS patients on Tysabri now 181--which means that 11 more have developed since the last reporting, according to the unofficial reporting site. Three of the 11 new cases are in the US. The new data can be seen here.
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PostPosted: Mon Dec 19, 2011 6:45 pm    Post subject: 12 new PML cases--total now 193 Reply with quote

The unofficial Website, chefarztfrau, has listed 12 new PML cases, 4 of them in the US, with the total now at 192.

The list can be seen here.


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PostPosted: Tue Dec 20, 2011 6:33 pm    Post subject: Reply with quote

These new figures have been posted on another Website, along with the information that there has been one additional death.
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PostPosted: Wed Dec 21, 2011 10:27 am    Post subject: Reply with quote

The total number of PML cases related to Tysabri is being given out as 193, but one of those cases is a Crohn's patient, and so I've subtracted it from the total given here.

A call to Biogen confirmed that as of December 1, there have been 192 cases of PML in MS patients on Tysabri. The total number of patients on Tysabri as of September was 92,200.
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PostPosted: Fri Jan 20, 2012 6:30 pm    Post subject: 9 more PML cases--total now 201 Reply with quote

As of January 4, 2012, there have been 9 new PML cases, making the total now 201. Of the 9 new cases, 6 have been in the US.

This information is from the chefarztfrau Website as well as from an article in MedPage Today on the FDA approval of the JC virus test to determine a patient's PML risk (January 20).
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PostPosted: Thu Feb 23, 2012 10:17 am    Post subject: 6 new cases--total now 207 Reply with quote

The chefarztfrau Website has listed 6 new cases of PML, and of those 4 are in the US.

The total is now 207.

Of the 207, 44 have died (21%).


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PostPosted: Thu Mar 08, 2012 11:30 am    Post subject: (Unofficial) 3 new PML cases, total now 210 Reply with quote

chefarztfrau lists three new PML cases:

208--Finland, male, 46 doses
209--Italy, female, 25 doses
210--France, male, 45 months

More data on the 207 cases previously reported:

201- US, female, 56 doses
202 - US, female, 61 doses
203 - France, male, 42 months
204 - Czech Republic, female, 31 months
205 - US, female, 47 doses
206 - US, male, 43 doses
207 - US, male, 59 doses

As of 12/31/11, 95,000 people have received Tysabri in the post-marketing phase, according to Biogen.
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PostPosted: Fri Mar 23, 2012 6:17 pm    Post subject: 2 new cases--total now 212 Reply with quote

The unofficial count is now 212. Two new cases, one with no information available, the other in the US.
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PostPosted: Fri Apr 20, 2012 6:12 pm    Post subject: 20 new PML cases, 3 more deaths Reply with quote

The unofficial source is listing 20 new PML cases, with the total now at 232.

Of the 20 new cases, 8 are known to be in the US. No information about the others is available.

There have been 3 more deaths. Now there will have been 49 Tysabri-related deaths due to PML (a death rate of 21%).
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PostPosted: Fri May 18, 2012 6:00 pm    Post subject: Total PML cases now 242 Reply with quote

There seem to have been 10 new PML cases, according to the chefarztfrau Website, bringing the total to 242. Of the 10 new cases, 2 are known to be in the US. The locations of the other cases aren't available.
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PostPosted: Tue Jun 05, 2012 5:17 pm    Post subject: 8 new cases Reply with quote

chefarztfrau is now listing a total of 250 PML cases, up from 242 last month.
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PostPosted: Fri Jun 22, 2012 4:42 pm    Post subject: 8 new cases--total now 258 Reply with quote

New data have appeared on the chefarztfrau Website. The total number of PML cases is now listed as 258--an increase of 6 cases since the last reporting.
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PostPosted: Thu Jul 26, 2012 7:59 am    Post subject: Total now 264 Reply with quote

Biogen Idec states that to date (7/23/12), there have now been 264 cases of PML. As of July 3, 2012, 58 of the 264 (22%) have died.

The total number of persons who are on Tysabri or who have ever been on Tysabri is still 99,600. Of those, 54,166 are in the US, and of those 54,166 in the US, 95 have developed PML.
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PostPosted: Fri Aug 24, 2012 9:55 am    Post subject: 7 new PML cases, total now 271 Reply with quote

Biogen Idec reports that as of 8/1/12, there have been 271 confirmed PML cases in connection with Tysabri. Of those, 2 appear to be in the US.

The total number of people who have ever taken Tysabri as of 6/30/12 is 104,300.

There have been 59 deaths among the 271 cases as of 8/1/12 (22%).

The PML risks associated with Tysabri increase after 2 years. For the first 24 months, a person's risk of PML while on Tysabri is less than 1 in 1,000 provided the two other risk factors aren't present (prior immunosupressive therapy and/or testing positive for the JC virus).

Between 25 and 48 months on Tysabri, a person's risk of PML would be 11 in 1,000 if the person tests positive for the JC virus and has had prior immunosuppressive therapy.
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PostPosted: Mon Sep 24, 2012 8:04 pm    Post subject: 14 new PML cases--total now 285 Reply with quote

The chefarztfrau Website has always been accurate in reporting PML cases in MS patients on Tysabri, and now lists 14 new cases, bringing the total to 285.

Of the 14 new cases, 5 are in the US. There have been 3 more deaths, and the total number of deaths is now 62 (22%).
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PostPosted: Fri Mar 08, 2013 12:14 pm    Post subject: 331 PML cases as of 2/5/13 Reply with quote

Biogen Idec reports that as of February 5, 2013, there have been 331 confirmed cases of PML associated with Tysabri.

This is based on a total of 112,181 patients who have ever received Tysabri for MS as of 12/31/12.

Of the 331 confirmed cases, 76 have been fatal. The Biogen representative stated that this is "about 20%." Actually it's 22.9%.
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PostPosted: Wed Jul 03, 2013 2:41 pm    Post subject: Now 372 PML cases, with 85 deaths Reply with quote

As of 6/4/13 the total number of confirmed Tysabri-related PML cases is 372, according to Biogen. That includes 2 cases of Crohn's disease.

Of the 372, 85 have died--a death rate of 22.84%, the same as in early April.

The total number of people who have ever taken Tysabri as of 3/31/13 is 115,365.
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PostPosted: Fri Aug 09, 2013 12:34 pm    Post subject: (Abst.) Risk factors risky to define: PML & Tysabri Reply with quote

From PubMed, August 9, 2013:

Quote:
Neurology. 2013 Aug 7.

Risk factors for rare diseases can be risky to define: PML and natalizumab

Major EO, Douek DC.

From the Laboratory of Molecular Medicine and Neuroscience, NINDS (E.O.M.), and Human Immunology Section, Vaccine Research Center, NIAID (D.C.D.), NIH, Bethesda, MD.

When rare neurologic diseases become topics of editorials in journals such as Nature Neuroscience,1 the New England Journal of Medicine,2 and Neurology®,3 there is usually something more of general interest than the rare disease itself. Such is the case for progressive multifocal leukoencephalopathy (PML), the JC virus-induced demyelinating disease that was once relegated for discussion to the back of the textbook, whether in microbiology or neurology.

Not any longer. Incidence and publication of cases of PML have risen more than 50-fold within the last decade. Renewed recognition of PML started in the mid-1980s, when it was recognized as an AIDS-defining illness in 1%-3% of all HIV-1-infected persons, still true in the era of combined antiretroviral therapy.4 PML is reported in patients with underlying neoplastic diseases, organ transplants, and rheumatic diseases, but by 2004, PML dramatically entered the mainstream as a serious adverse event associated with a promising monoclonal antibody therapy, natalizumab, for treatment of relapsing-remitting multiple sclerosis (MS).

Nature itself showed that demyelinating diseases of substantially different etiologies and pathologies can occur in the same brain, and remarkably enough in some cases, not with a fatal outcome. In 2006, the estimated occurrence of PML in natalizumab-treated patients with MS, with an average treatment of 17 months, was 1 per 1,000.5 With more than 115,000 patients globally treated with natalizumab for longer periods of time, that estimate is 1 per 330.6 In patients who test positive for antibodies to JCV, have a clinical history of immune suppressive treatment before natalizumab, and have received more than 24 doses, the number of PML cases is 1 per 90.

PMID: 23925759


The abstract can be seen here.
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PostPosted: Fri Oct 11, 2013 5:54 pm    Post subject: (Abst.) MS & the Iranian revolution Reply with quote

From PubMed, October 11, 2013:



Quote:
J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2.

MULTIPLE SCLEROSIS AND THE IRANIAN REVOLUTION.

Pakpoor J, Ramagopalan S.

University of Oxford; Barts and the London School of Medicine and Dentistry.

Multiple Sclerosis (MS) is a complex neurological disorder most likely caused by gene-environment interactions. There is a latitudinal gradient of MS prevalence, and vitamin D deficiency has been strongly implicated in MS aetiology.

Iran is a country of high levels of sunshine which has previously been considered a low-risk MS region. However, Iran has recently observed an 8.3-fold rise in the incidence of MS between 1989-2006.1 Previous studies have indicated a genetic predisposition to MS in the Iranian population but genetic changes are unlikely to account for the substantial rise in MS over the last few decades. Thus, we aimed to develop a novel hypothesis to explain the identification of Iran as a high-risk MS region.

We believe that the influence of decreased sunshine exposure and vitamin D levels on MS risk needs to be strongly considered in the context of Iran's history. In 1979 the Iranian Revolution took place and a country previously under great Western influences became an Islamic republic. It became a government requirement for women to wear loose-fitting clothing and the veil in public; it has previously been shown that veiled women have lower vitamin D levels compared to unveiled women. This significant cultural shift would not only potentially explain the observed increase in MS but notably, it would account for the increasing female preponderance of MS in Iran. Given that the average age of MS onset is 30 years old and that MS incidence in Iran just over 30 years following the revolution is the highest so far recorded, an association with the Iranian revolution and reduced subsequent vitamin D levels, particularly in pregnant women, is likely.

Lifestyle changes such as urbanization and use of sunscreen may to some extent have contributed to increased vitamin D deficiency, but these are unlikely to contribute to the particularly high increase in MS observed in Iran as these changes occurred across the developed world and there is no evidence to suggest that they were particularly great in Iran. A similar high incidence of MS has been observed among Iranian immigrants in countries at high latitude such as Sweden where Iranian immigrants have a reported greater prevalence of MS compared to the general population, despite wearing a veil not being a requirement. Instead it is well-known that UVB exposure is lower in countries at high latitude and thus, a similar effect of increased MS incidence due to vitamin D deficiency may be observed among those in Iran wearing the veil and those resident in countries at high latitude, even if they are not wearing the veil. Therefore, vitamin D repletion is a critical public health issue for Iranians both within and outside Iran, and could help prevent an emerging MS epidemic in this population.

More generally, this region is highly interesting for MS research and highlights that regions of exception to the latitudinal gradient of MS prevalence are an under-appreciated and very useful resource in evaluating MS aetiology.



The abstract can be seen here.
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PostPosted: Mon Oct 14, 2013 1:40 pm    Post subject: 401 PML cases as of 9/3/13 Reply with quote

The unofficial chefarztfrau Website is listing 401 cases of Tysabri-related PML as of 9/3/13.
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