While reading another board I came across a post about Rituxan and PML:

"Thomas Gryta's article today published by Dow Jones about the PML consortium got me to go back and review what I have about the relative incidence of PML (fatal and non-fatal) in Tysabri vs. Rituxan, particularly given a recently acknowledged third fatality from PML in a Rituxan patient. In his article, Gryta stated that “PML has been most frequent in users of Tysabri, with 24 confirmed cases since its re-launch in 2006.

While there have been just three “officially” acknowledged fatalities from PML among at least 57 PML cases in the approximately 100,000 patients who have ever taken Rituxan, there may be many more fatalities than are acknowledged by Biogen Idec, Genentech and Roche. See the October 2009 notification from Biogen Idec and Genentech
(http://www.fda.gov/downloads/Safety/.../UCM187792.pdf) as well as a similar November 9, 2009 notification from Roche sent to medical professionals in Europe.

A total of 57 PML cases, 51 of which were fatal, was reported in an article by Charles Bennett, MD of Northwestern University and colleagues, published in the May 14, 2009 issue of the medical journal Blood *, covering the period 1997 through 2008. According to Dr. Bennett and his colleagues, of the 51 fatalities among the 57 PML patients identified, the median time between their diagnosis and death was about two months.
I find it very curious that neither the FDA, the EMEA, Biogen Idec, Genentech nor Roche mention the other approximately 54 PML cases in patients taking Rituxan, nor the fact that there were an additional 48 fatalities identified by Bennett et al., just the three fatal cases acknowledged by the drug companies. Of course, there is no TOUCH-like risk management plan in place for Rituxan, so some Rituxan-related PML cases and even some fatal PML cases may have been missed.

So, how does the current total of 24 cases of PML in Tysabri (including four fatal cases) among 60,700 total Tysabri patients compare to the 2008 total of 57 cases of PML in Rituxan (including at least three and possibly 51 fatal cases) among 100,000 total Rituxan patients? My understanding is that Rituxan is generally used short term, while Tysabri is generally used indefinitely. It would appear that the incidence of PML in Tysabri patients taking the drug for less than two years is fairly low compared to the incidence of PML in Rituxan patients (most of whom, as I understand it, take the drug for two years and less).

Why is Rituxan being treated differently than Tysabri with regard to both fatal and non-fatal cases of PML? It is likely the history of Tysabri being removed from the market and then fighting to get US re-approval, coming on the back of the Vioxx withdrawal, while Rituxan has been on the market for 12 years or so, and the fact that there appears to be some link between Tysabri-related PML and duration of use beyond two years.

* An abstract of the Bennett et al. article as well as links to the full article are pasted below. The Bennett et al. article was reported in a May 20, 2009 article published by Northwestern University (http://www.northwestern.edu/newscent...5/bennett.html) as well as a June 1, 2009 article by Gryta''s colleague Alicia Mundy in the Wall Street Journal (http://online.wsj.com/article/SB124381351149970563.html).

Blood, 14 May 2009, Vol. 113, No. 20, pp. 4834-4840.
Prepublished online as a Blood First Edition Paper on March 5, 2009; DOI 10.1182/blood-2008-10-186999.

Full article: http://bloodjournal.hematologylibrar...urcetype=HWCIT

PDF of full article: http://bloodjournal.hematologylibrar...urcetype=HWCIT

Abstract: http://bloodjournal.hematologylibrar...urcetype=HWCIT


Another poster responds:

PML Incidence in Tysabri vs. Rituxan (ASCO study says survival rate after PML diagnosis in Rituxan treated patients was 3 or 9% out of 35 cases studied).
"Rituximab and progressive multifocal leukoencephalopathy: A report of 35 cases." 2008 ASCO report
at http://www.asco.org/ASCOv2/Meetings/...stractID=33229
In the abstract of the above study it states:
"Results: Of 51 unique cases identified, 2 were excluded for HIV, and 14 for inadequate confirmation of PML. In the 35 remaining cases, survival for 1 year after PML diagnosis was reported in just three patients (9%)."

A comment from the responder:

"It seems that deaths associated with PML in Rituxan-treated patients are not being reported or publicized in the media. It is a very good question you raise regarding why Tysabri is being treated differently than Rituxan with regards to associated PML."

(thanks to LJD and vl for above information!)