Disease-free on Tysabri?

TwistedHelix · Post by **TwistedHelix** » Mon Oct 15, 2007 6:05 am

12 October 2007, 14:57:35
Study Shows Increased Proportion of Patients Achieve Disease-Free Status with TYSABRI - Separate Study Demonstrates Plasma Exchange May Be an Effective Tool to Accelerate TYSABRI Removal.

Biogen Idec and Elan Corporation, plc announced that TYSABRI® (natalizumab) treatment significantly increases the proportion of disease-free patients with multiple sclerosis (MS) according to a post hoc analysis of the Phase III AFFIRM study to be presented on Saturday, October 13, 2007 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague, Czech Republic. Also to be presented on Saturday will be findings from the PLEX study which suggest that plasma exchange may be an effective means of accelerating the removal of TYSABRI from the circulation.

Post Hoc Analysis of Phase III AFFIRM Study

The proportion of disease-free patients in the AFFIRM study was determined based upon clinical and MRI criteria. The proportion of disease-free patients over two years was significantly higher in the TYSABRI-treated group compared with the placebo group regardless of how disease free was defined.

Clinically, disease free was defined as no relapses and no progression of disability (as defined by > or =1.0-point increase in Expanded Disability Status Scale (EDSS) score from a baseline score of > or =1.0, or a > or =1.5-point increase from a baseline score of 0.0, sustained for 12 weeks) over two years. MRI disease free was defined as no gadolinium-enhancing lesions and no new or enlarging T2-hyperintense lesions.

Using clinical and MRI disease-free criteria combined, the most stringent definition of disease free, 36.7% of TYSABRI-treated patients had no relapses, disability progression or MRI activity compared with 7.2% of placebo patients (p<0.0001). In the clinical analysis, 64.3% of TYSABRI-treated patients vs. 38.9% placebo-treated patients(p<0.0001) were disease free or without relapses and disability progression. Using MRI measures, 57.7% of TYSABRI-treated patients vs. 14.2% placebo-treated patients (p<0.0001); were disease free, or without gadolinium-enhancing lesions and new or enlarging T2-hyperintense lesions.

"These data demonstrate the dramatic effect TYSABRI can have on critical measures of multiple sclerosis. In addition to the impact on individual clinical and MRI outcomes, it is striking that more than one-third of patients were free of relapses, disability progression and MRI activity after two years of treatment. This suggests that TYSABRI may offer patients freedom from many of their MS symptoms," said Eva Havrdova, MD, PhD, Director of the Center for Demyelinating Diseases at the First School of Medicine, General University Hospital, Charles University, Prague, Czech Republic.

LisaBee · Post by **LisaBee** » Tue Oct 16, 2007 5:18 pm

This is interesting. I'm assuming, since they mention placebo, it is at least a single-blinded study. It looks like from a clinical perspective, nearly two thirds of Tysabri patients met the criteria "disease free" but nearly 40% of the placebo patients also met that criteria.
In terms of MRI activity, 57.7% met disease free for Tysabri versus only 14.2% for placebo.
Yet for disease free by BOTH clinical and MRI measures, only 36.7% met the criteria for the Tysabri group. versus 7.2% for placebo.

Looking at the Tysabri group alone for a second, this indicates that a lot more people met disease free by one criteria or the other, but not both. This indicates what people have already indicated based on studies and personal experience, that MRI activity does not always correlate with disability progression.

Looking at the placebo group alone a second, a significant number of placebos show no clinical progression, but very few, 14%, have no MRI activity.

Looking at Tysabri versus placebo - it looks like Tysabri does proportionately better. relative to placebo, at reducing activity on the MRI than it does in reducing disability progression. It does appear to reduce disability progression versus placebo, but in less people than I would have hoped. However, time will tell - two years is not that long on assessing disability endpoints - the next two years will tell whether Tysabri only delays disability progression, or it actually holds the line in the clinical responders - I hope for the latter.

About 30 percent of Tysabri patients weren't helped in terms of clinical outcome. I am curious how many of these 30% had no MRI activity, but yet progressed in disability. That always suggest to me that something non-immune related is going on in that subset.

It gets back to MS subsets, just like with the CRABs some people respond, and some don't.

People who have followed the CRAB data two years out - how does Tysabri compare at this point? It looks better to what I remember for CRABs at the two year mark - but I don't want to rely on my memory.

Lyon · Post by **Lyon** » Tue Oct 16, 2007 7:38 pm

LisaBee wrote: About 30 percent of Tysabri patients weren't helped in terms of clinical outcome. I am curious how many of these 30% had no MRI activity, but yet progressed in disability. That always suggest to me that something non-immune related is going on in that subset.

Hi Lisa,
Just to throw my 2 cents in

There has been a lot of speculation about this, not just involving Tysabri results and it's important to keep in mind that lack of mri activity in essence means lack of activity that our imaging is capable of picking up and not specifically lack of activity.

I'm not sure how anyone else considers the situation, but going with the odds it's always seemed far more likely to me that neurodegeneration continues due to diffuse, low grade inflammation which our imaging isn't capable of picking up (ie..a lesser degree of the same thing it's always done), as opposed to the disease mechanism actually changing.

Not that I can prove that is the case, there is no conclusive evidence in MS research to this point, but it seems a logical consideration.

Bob

robbie · Post by **robbie** » Wed Oct 17, 2007 5:59 am

About 30 percent of Tysabri patients weren't helped

3 out of 10 people WOW, you gotta be one lucky son of a bitch to get any benefit here.

HarryZ · Post by **HarryZ** » Wed Oct 17, 2007 11:22 am

Lisabee,

I really enjoyed reading your analysis and view of what this data means when it comes to what kind of real benefit the current MS drugs give us.

Biogen is very good at taking bits and pieces of information from trials and making it sound that a drug like Tysabri is absolutely wonderful in treating MS patients. I suspect that in the long run, Tysabri may be slightly better than the pretty much useless CRABs but you have to ask yourself if the huge expense of it merits its wide spread use. I guess time will tell.

Harry

ewizabeth · Post by **ewizabeth** » Wed Oct 17, 2007 7:38 pm

Hi All,

My doctor is an MS neuro. He thinks that Rebif is the best of the ABCR's, and Tysabri has shown slightly better results in trials.

The good thing about Tysabri of course is, the lesser amount of undesirable side effects.

I just had my 6th infusion today, and my energy and strength as improved somewhat. I was a non-believer until I felt it for myself. Is it worth the expense? My insurance is good, so I have to say ABSOLUTELY! it's worth the expense. We're only paying about $90 monthly out of pocket, compared to $6.67 a month for the ABCR's. With the qol improvements, I say yes, it's worth it.

I didn't notice any improvements until about the 5th infusion. I do have an increase of bladder symptoms, but I can live with that.

Sorry to get off topic here.

Lyon · Post by **Lyon** » Thu Oct 18, 2007 4:22 am

ewizabeth wrote:Sorry to get off topic here. Smile

Hi ewizabeth,
Seems like nothing could be more ON topic!

I'm glad to hear that you're still satisfied with your decision. I read recently that 17,000 people have been infused with Tysabri since the PML scare with no reported cases of PML.

ewizabeth wrote:My doctor is an MS neuro. He thinks that Rebif is the best of the ABCR's, and Tysabri has shown slightly better results in trials.

HarryZ wrote: Biogen is very good at taking bits and pieces of information from trials and making it sound that a drug like Tysabri is absolutely wonderful in treating MS patients. I suspect that in the long run, Tysabri may be slightly better than the pretty much useless CRABs

Ewizabeth, I don't really follow Tysabri but that's twice in the last few days I've read the same thing. Originally Tysabri was reputed to be about twice as effective as the crabs, is there now reason to think that it's only slightly better than the crabs?

Bob

ewizabeth · Post by **ewizabeth** » Thu Oct 18, 2007 5:40 pm

Hi Bob,

I'm no statistician, but my neuro conducts trials continuously, and I'm sure he understands these things a lot better than any of us. He said it's better than Rebif, but not that much better. But when you look at the side effects that many people get with Rebif, that means a lot too, plus you have to do injections.

When I was on Rebif, and I went up to 44mcg, I developed severe depression and panic attacks, etc... At one point I didn't even want to leave one room of the house it was so bad, couldn't take phone calls, or handle stress at all.

When I think of how good I feel right now on Tysabri, and it's better than Rebif (which I can't handle anyway!!) I'm extremely happy with my decision!

I had my infusion yesterday, and I felt good even though I was tired from the trip to the doctor.

So far, I'm thrilled with the results, and I hope I can keep taking it and benefiting from it for a long time.

P.S. He says Rebif has ~60% efficacy and Tysabri is around ~70% efficacy, give a point or two either way for both of them. (And I'm saying this from memory, but you get my drift.)

HarryZ · Post by **HarryZ** » Thu Oct 18, 2007 6:10 pm

P.S. He says Rebif has ~60% efficacy and Tysabri is around ~70% efficacy, give a point or two either way for both of them. (And I'm saying this from memory, but you get my drift.)

In all the trials and stats that I have ever seen about Rebif, I must admit that I have never seen any numbers anywhere close to 60% efficacy for this drug. I wonder where your neuro has obtained these stats.

Harry

Lyon · Post by **Lyon** » Thu Oct 18, 2007 6:19 pm

ewizabeth wrote: P.S. He says Rebif has ~60% efficacy and Tysabri is around ~70% efficacy, give a point or two either way for both of them. (And I'm saying this from memory, but you get my drift.)

Hi ewizabeth,
I'm glad you added the above because it helps make sense of the situation for me. The

Tysabri has shown slightly better results in trials

comment didn't align with anything I've ever read in comparisons between Tysabri and the crabs.

I'm not in a position to disagree with your neuro's estimates but EVERYTHING I've ever read puts all of the crabs in the lower 30's and Tysabri anywhere from 50-70%, which is just about double.

At any rate, when it comes to something as important as your brain, when even a couple percentage point advantage is priceless, and when you consider the other advantages (no shots, no depression, etc..) I don't blame you for being happy with your decision!

Bob

ewizabeth · Post by **ewizabeth** » Thu Oct 18, 2007 6:26 pm

HarryZ wrote:
P.S. He says Rebif has ~60% efficacy and Tysabri is around ~70% efficacy, give a point or two either way for both of them. (And I'm saying this from memory, but you get my drift.)
In all the trials and stats that I have ever seen about Rebif, I must admit that I have never seen any numbers anywhere close to 60% efficacy for this drug. I wonder where your neuro has obtained these stats.

Harry

Harry,

I don't know, but I remember XO++ (Mark) saying something similar over on BT awhile back, (I think.)

HarryZ · Post by **HarryZ** » Thu Oct 18, 2007 6:37 pm

Ewizabeth,

I don't know, but I remember XO++ (Mark) saying something similar over on BT awhile back, (I think.)

It was some time ago and he was comparing the relative numbers between the CRABs and Tysabri. I think he showed that Tysabri was about 12% better than the CRABs or something like that.

Harry

ewizabeth · Post by **ewizabeth** » Thu Oct 18, 2007 6:52 pm

Harry,

Maybe it's the same sort of stats my neuro uses. Maybe it really means something. He's pretty heavy into this stuff, he had a large site for the Tysabri phase III trials.

HarryZ · Post by **HarryZ** » Thu Oct 18, 2007 7:01 pm

ewizabeth wrote:Harry,

Maybe it's the same sort of stats my neuro uses. Maybe it really means something. He's pretty heavy into this stuff, he had a large site for the Tysabri phase III trials.

Ewizabeth,

My wife's neuro was also involved in the Tysabri Phase III trials with several patients. When I spoke to him a couple of years ago, he told me that they didn't see that much of an improvement with their patient group. He also told me at the time that Biogen had a reputation for not being exactly trusted in the MS world of medicine when it came to information.

He also thought that Tysabri would be good for new and very mild cases sof MS but not much beyond that.

Harry

Lyon · Post by **Lyon** » Thu Oct 18, 2007 7:20 pm

HarryZ wrote:When I spoke to him a couple of years ago, he told me that they didn't see that much of an improvement with their patient group.

Hi Harry,
What do you think he meant by that? Not much of an improvement of symptoms or not much slowing down of progression?
Bob