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Just saw this article from Reuters re: PML showing up in a couple of Rituxan patients. Although the drug has been used for about 8 years with supposedly good safety results, one has to wonder why PML has decided to all of a sudden show up. I would hope that those MS patients involved in clinical trials with Rituxan will be closely monitored.

Harry

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WASHINGTON (Reuters) - Two lupus patients died from a rare brain infection after taking the Genentech and Biogen Idec drug Rituxan, U.S. health officials said in an advisory issued on Monday.

Rituxan, authorized for lymphoma and rheumatoid arthritis, is not approved for treating lupus but doctors sometimes prescribe it for that use, the U.S. Food and Drug Administration said in a notice posted on its Web site.

Both patients died from a brain infection called progressive multifocal leukoencephalopathy, or PML, the FDA said. The agency urged doctors to discuss the chances of PML with Rituxan patients, saying there is no known treatment.

Rituxan's prescribing instructions already include information about reports of several types of viral infections, including PML, that became active again or worsened in cancer patients taking Rituxan.

"FDA is working to gather more information about Rituxan and PML and to strengthen the warnings about PML in the Rituxan product label," the agency said.

Biogen said it and Genentech issued a letter to doctors about the patients with lupus, an autoimmune disease.

Genentech spokeswoman Debra Charlesworth said clinical trials of Rituxan were ongoing for lupus and other conditions. The two lupus patients who died were not enrolled in a clinical trial, she said

According to the article I read, Rituxan has been linked to 23 other cases of PML in its use as a cancer drug. Sobering info, really. I think the bottom line is that this class of drugs (monoclonal antibodies) that fundamentally alter the workings of the immune system will have repercussions beyond what is expected.

This is bad news, as Rituxan is the one drug in trials for PPMS, and I have PPMS...

I do wonder what other drugs these patients may have been taking. I know with the use as a cancer drug, it is given with steroids and other concoctions. Unfortunately with the cancer treatments, death is certain without this treatment is many cancer patients. Search Devic's or NMO with Rituxan and see if any PML is showing up there. RA is another illness Rituxan is used for. Recently approved by FDA

I'm a little late chiming in here (as if anybody really wants me to anyway), but every time something like this (problem with Rituxan) comes up long after I expressed my doubts and why and been chastised by others to the point of me just finally giving up and going away, I can't help but pop back in now.

Back in October, 2005, (note the date there) I was having an MS discussion with a physician/researcher (former friend) at Vanderbilt. After reading the below, can someone tell me AGAIN why it is/was that more research money is being dumped into something that upon simple reflection does not indicate itself to be really that effective for the treatment MS? And that the risks may not be worth it? (If someone as simple as I am can surmise that long beforehand, you can't tell me the "experts" can't do the same!?)

Here are excerpts from my email discussions with Vanderbilt (you'll once again see how outspoken I am or was, anyway. Although, you might see how I tried to "soften" up my responses to them. I finally gave up talking to them altogether.) And yes, I'm no fan of Biogen, either. No secret there, either.

(And to those who are fans of the "mabs", don't worry, I wasn't listened to and I'm sure will never be, so I pose no real threat to current MS research.)

Part of some questions proposed to me (in blue) and my answers:

Date: Monday, October 24, 2005

Is CNS apoptosis an important event in MS?

Depends. I'd say not apoptosis of the B cells, though. Not as a major factor. But yes, it's complex, but there is obvious dysfunction of cell death........macrophages, neurons..........I refer to it as "it's all in the timing".

Now having said all that, everything hinges on which pattern of MS we are referring to. And yes, I have read more and more about the PNS in connection to MS. (Remember, also, that recent ALS research on desipramine found that it has excellent CNS penetration.) Speaking, though, of the traditionally thought of PPMS as currently defined, then I'd say apoptosis is a part of it, but maybe not the "initial" event. I think PPMS is an altogether different puppy than RRMS or SPMS.

I may not be able to speak ALL the jargon off the top of my head without referring to my previous research, but there isn't much I haven't read and studied about all this. I'm no expert by any means, but maybe a fresh viewpoint might at least present some new ideas?

Then my follow-up email to them the following day, because Vandy had mentioned B cells and the PNS (peripheral nervous system):

Date: Tuesday, October 25, 2005

Ok...........I see........ they have tested rituximab on B lymphocytes in progressive MS (and basically failed). (I won't post the results I found, but I have it.) (As shown below, if somebody would have read the pharmacology of rituximab before even expending any time and money on a clinical trial of it on progressive MS, they would have seen that it was unlikely to work in the CNS.) What a waste! But..........ok!

Of course, as just mentioned above when researching the pharmacology of rituximab during lunch just now, that drug does not penetrate the CNS, it only DOES its work in the periphery: "Rituximab binding was observed on lymphoid cells in the thymus, the white pulp of the spleen, and a majority of B lymphocytes in peripheral blood and lymph nodes." BUT, of course, notice the EXTREME coincidence, this AGAIN is being "pushed" by Biogen! I think I'm going to die laughing! God, I rest my case! (Biogen and "mabs". They'll never stop, will they?) I had NO idea I'd run across Biogen AGAIN when following up on this! I swear!!!

Ok, if you DO want to see what happens when you affect B lymphocytes in the CNS in progressive MS, again I tell ya............try desipramine. It also lowers B lymphocytes in the CNS and raises IL10 at the same time. Yes, I have mounds of research to support this claim.

I'm dying laughing. Biogen has got to be buying you guys dinner constantly! hehehe......................

That's ok.............I luv ya anyway.............even if you folks do get manipulated by them. (Yes, I know it wasn't you...........it was done in Texas, but I gotta rag on ya anyway.)

MY advice? Forget the "mabs". They are nothing but trouble and won't work in the long run anyway.

EDIT: Oh, and please remember, this is only my opinion. My opinions don't hold any weight.

I also meant to add that I hope everyone had wonderful holidays, and Happy New Year to all! All the best!

Though the data has not been released yet, initial reports are that the trial of Rituxan for PPMS have had some success. My neurologist, one of the top two or three here in New York City, has suddenly changed his tune on the drug. Two years ago he completely shot me down when I first mentioned Rituxan; now he is discussing it as a treatment option, and has told me that indications are it may be very effective for PPMS.

We'll have to see what the data from the trial looks like. I believe it's due to be released sometime early this year.

It still boils down to some treatments help some people and will not others. I think it is OUR burden as patients and caregivers to seek out the treatment best for us. Otherwise, you can be thrown into the "general pool" of treatments. The CRABs being among those. I know of people that Avonex seems to have helped and others that it did more harm than good. Copaxon is the same way. Tysabri and Rituxan will be in that as well. If you are facing a life of complete or near complete paralysis, then the risk factor is not as much concern to you. If you drag a leg once in a blue moon, the risk of PML or other adverse reactions may be too much for you to risk. This MS thing will come down to many different types beyond the RRMS, PPMS, or SPMS types. Maybe this is the year of change in research.