Tysabri und PML-Gefahr -
mein Freund war in der gleichen Situation, weshalb er mich gebeten hat, Hintergrundinformationen zu dieser angeblichen “Killerdroge” zu beschaffen.
Anbei die Fakten zu den 3 bisherigen PML-Fällen aus den “Briefing Documents” Tysabri zur Behandlung von MorbusCrohn ab Seite 58ff:
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4313b1-01-FDA.pdf
2 der 3 PML-Fälle sind in der SENTINEL-Studie aufgetreten, in welcher eine kombinierte Therapie von Avonex und Tysabri stattgefunden hat → deswegen ist Tysabri nur in Monotherapie zugelassen. Eine gleichzeitige Gabe von Interferonen oder anderen immunmodulierenden bzw. immunsupprimierenden Medis ist nicht gestattet.
Der 3. PML-Fall ist in einer Morbus-Crohn-Studie aufgetreten, wobei die betroffene Person einen ganzen Arzneimittelcocktail vorab zu sich genommen hat u.a. Azathioprin, wodurch die Immunabwehr nachhaltig geschwächt war.
In Monotherapie, also Tysabri ohne irgendwelche immunmodulierenden bzw. immunsupprimierenden Medikamente, ist bisher kein PML-Fall aufgetreten -
und bis zum 23.5.07 wurde immerhin schon 11.500 Menschen damit therapiert - aktuell sind es über 14.000:
• The TYSABRI RiskMAP for MS patients, has been successfully implemented.
Compliance with the program is excellent and there is a high degree of awareness of
PML risk among patients and prescribers. From time of re-introduction in June 2006
until May 23, 2007, approximately 11,500 patients have received TYSABRI
worldwide in the post-marketing setting, of which approximately 8,300 patients have
been dosed in the US. Although long-term exposure data are limited, there have been
no new confirmed cases of PML or other serious OI’s reported.
Seite 9 → http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4313b1-03-Biogen.pdf
PML Case 1 (reported by Kleinschmidt-DeMasters)
This was a 46 year-old woman with RRMS that was participating in Study 1802 (the Avonex add-on study) when she died from PML. The patient’s MS symptoms began in 1999 and treatment with Avonex was initiated in February 2000. The patient began receiving natalizumab 300 mg IV every 4 weeks on April 12, 2002, and received her last dose on January 18, 2005. This patient received a total of 37 natalizumab infusions. Also, this patient had three times received methylprednisolone intermittently for five days at a time March 16-20, 2002, December 15-19, 2004, and January 5-9, 2005. Symptoms of PML began in November 2004 with increased difficulty with eye-hand coordination and problems with her speech. These FDA Advisory Committee Briefing Document • Natalizumab (Tysabri) for Crohn’s Disease •
page 59 of 109
7/3/2007
symptoms progressively worsened and she was treated with methylprednisolone twice (as described above) because she was initially thought to have worsening MS. Significant MRI changes were seen in mid-December 2004; the last natalizumab treatment she received was in January 2005. This patient continued to decline; she eventually had a positive CSF JCV DNA in . She died later that month. An autopsy was conducted which confirmed PML.
PML Case 2 (reported by Langer-Gould)
This was a 46 year-old man with RRMS who was also in Study 1802 (the Avonex add-on
study). This patient was on Avonex and had received a total of 28 natalizumab infusions. It should be noted that a routine MRI in October 2004 revealed a new atypical frontal lobe lesion, but the patient was asymptomatic at that time. This lesion was later identified as PML, but it had not been immediately recognized as such. This patient was noted to have atypical behavior during a visit to a doctor one month later. By mid-December, this patient had developed worsening symptoms; a repeat brain MRI revealed new lesions consistent with PML.
Natalizumab was stopped in mid-December. In February, JCV DNA in serum and CSF were
positive, as was a brain biopsy for PML. Avonex was stopped in February 2005. This patient continued to decline despite being treated with multiple medications, but eventually stabilized, and improved, but remains severely disabled.
PML Case 3 (reported by Van Assche)
This was a 60 year-old Crohn’s disease patient who had been treated intermittently with
natalizumab and immunosuppressive agents who died from what was initially thought to be an astrocytoma, but was retrospectively on pathology specimen determined to be PML. This patient had a significant history of immunosuppressive use. Beginning in March 2002, this patient received three doses of natalizumab given concomitantly with azothioprine. The patient then entered the placebo arm of a continuation study, and stopped natalizumab. The patient was on placebo and azothioprine until November 2002, when he had to stop the azothioprine due to pancytopenia. The patient was off of immunosuppressive agents altogether until February 2003 when the patient began open-label treatment with natalizumab infusions. In July 2003, after five consecutive natalizumab doses (total of eight doses), the patient presented with a one week history of cognitive decline. A brain MRI revealed a frontal lesion for which the patient underwent partial resection and was diagnosed with anaplastic astrocytoma, WHO
Grade III. The patient was treated with steroids and anticonvulsants, but died in
. The sponsor re-evaluated the pathology slides and found that the patient actually had
PML. Retrospective analysis of stored serum samples from the patient demonstrated detectable JCV DNA two months before clinical presentation. It was noted that the serum JC DNA increased in number over the time leading up to clinical presentation.
Ich würde dir empfehlen, das Risiko mit deinem Neurologen noch einmal zu diskutieren. Mein Freund war nach Durchsicht der Daten und Fakten bzgl. Verringerung der Schubrate und Gefahr der Nebenwirkungen voll überzeugt, dass Tysabri das beste Medikament zur Behandlung der MS darstellt. Am 2. Mai 2007 hat er seine erste Infusion bekommen und bis auf eine 2 Tage nach der Infusion anhaltende Müdigkeit verträgt er es bestens.
