2nd infusion redux

A board to discuss the newly-released drug Tysabri, (formerly known as Antegren) as a treatment for Multiple Sclerosis

2nd infusion redux

Postby leeeeeway » Fri Sep 08, 2006 9:32 am

I hesitate to tell the list this until I know something more definite but 7 minutes into my 2nd Tysabri infusion on Wednesday I had an anti-phylactic (allergic) reaction. Turned bright red, couldn't breath and felt like the top of my head was going to explode. Also managed to lose my breakfast. The nurse turned off the Tysabri and gave me Benedril and 250 mg of solumedrol. Not fun but all I could think was "Dammit! I want this drug!"

I had blood drawn yesterday which will be sent today to one of 2 labs Biogen has contracted with to see if I have Tysabri antibodies. If I do then I won't be able to take the drug. If I don't then MAYBE I can start back again on a slower dose, premedicated, etc. (This is my 4th infusion, second in latest go around for all you keeping score) They made an appt for my next infusion anyway.

My neuro is going to a mtg of Tysabri infusion providers this weekend and hopefully will come back with something useful for me...in the mean time all I can thing is antibodies...

Lee
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Postby amelia » Fri Sep 08, 2006 2:57 pm

I know someone on this group has the data I am looking for;
What is the percentage of people who had an allergic reaction to
Tysabri?
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Postby HarryZ » Fri Sep 08, 2006 4:21 pm

Amelia,

amelia wrote:I know someone on this group has the data I am looking for; What is the percentage of people who had an allergic reaction to
Tysabri?


Here is the data you are looking for. I'm thinking that if one were to get a serious adverse reaction to Tysabri, it would happen during the first infusion, not 2 or 3 infusions later. Perhaps as Lee said, his system may have developed anti-bodies to the drug and that's why he experienced this serious problem at this point in time.

Harry

___________________________________

ABSTRACT

Background Natalizumab is the first 4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis.

Methods Of a total of 942 patients, 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years.

Results Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan–Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by gadolinium-enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were fatigue (27 percent vs. 21 percent, P=0.048) and allergic reaction (9 percent vs. 4 percent, P=0.012). Hypersensitivity reactions of any kind occurred in 25 patients receiving natalizumab (4 percent), and serious hypersensitivity reactions occurred in 8 patients (1 percent
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Tysabri Antibodies

Postby MetsFan » Sat Sep 09, 2006 10:31 am

Amelia: The short answer is that 9% develop antibodies at least once and 6% develop persistent antibodies.

Look at www.Tysabri.com under Product Information


PAGE 9

Hypersensitivity
TYSABRI® has been associated with hypersensitivity reactions, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%. These reactions usually occur within 2 hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. Generally, these reactions are associated with antibodies to TYSABRI®.
If a hypersensitivity reaction occurs, discontinue administration of TYSABRI® and initiate appropriate therapy (see ADVERSE REACTIONS, Infusion-related Reactions). Patients who experience a hypersensitivity reaction should not be re-treated with TYSABRI®. The possibility of antibodies to TYSABRI® should be considered in patients who have hypersensitivity reactions (see ADVERSE REACTIONS, Immunogenicity).


PAGE 14
Infusion-related Reactions (see WARNINGS, Hypersensitivity)
An infusion-related reaction was defined in clinical trials as any adverse event occurring within 2 hours of the start of an infusion. Approximately 24% of TYSABRI®-treated multiple sclerosis patients experienced an infusion-related reaction, compared to 18% of placebo-treated patients. Events more common in the TYSABRI®-treated patients included headache, dizziness, fatigue, urticaria, pruritus, and rigors. Acute urticaria was observed in approximately 2% of patients. Other hypersensitivity reactions were observed in 1% of patients receiving TYSABRI®. Serious systemic hypersensitivity infusion reactions occurred in <1% of patients. All patients recovered with treatment and/or discontinuation of the infusion.
Patients who became persistently positive for antibodies to TYSABRI® were more likely to have an infusion-related reaction than those who were antibody-negative (see ADVERSE REACTIONS, Immunogenicity).

Immunogenicity
Patients in Study 1 were tested for antibodies to natalizumab every 12 weeks. The assays used were unable to detect low to moderate levels of antibodies to natalizumab. Approximately 9% of patients receiving TYSABRI® developed detectable antibodies at least once during treatment. Approximately 6% of patients had positive antibodies on more than one occasion. Approximately 82% of patients who became persistently antibody-positive developed detectable antibodies by 12 weeks. Anti-natalizumab antibodies were neutralizing in vitro.
The presence of anti-natalizumab antibodies was correlated with a reduction in serum natalizumab levels. In Study 1, the Week 12 pre-infusion mean natalizumab serum concentration in antibody-negative patients was 14.9 mcg/mL compared to 1.3 mcg/mL in antibody-positive patients. Persistent antibody-positivity was associated with a substantial decrease in the effectiveness of TYSABRI®. The risk of increased disability and the annualized relapse rate were similar in persistently antibody-positive TYSABRI®-treated patients and patients who received placebo. A similar phenomenon was also observed in Study 2.
Infusion-related reactions most often associated with persistent antibody-positivity included urticaria, rigors, nausea, vomiting, headache, flushing, dizziness, pruritus, tremor, feeling cold, and pyrexia. Additional adverse events more common in persistently antibody-positive patients included myalgia, hypertension, dyspnea, anxiety, and tachycardia.
If the presence of persistent antibodies is suspected, antibody testing should be performed. Antibodies may be detected and confirmed with sequential serum antibody tests. Antibodies detected early in the treatment course (e.g., within the first 6 months) may be transient and disappear with continued dosing. Repeat testing at 3 months after the initial positive result is recommended in patients in whom antibodies are detected to confirm that antibodies are persistent. Prescribers should consider the overall benefits and risks of TYSABRI® in a patient with persistent antibodies.
The long-term immunogenicity of TYSABRI® and the effects of low to moderate levels of antibody to natalizumab are unknown. Experience with other monoclonal antibodies suggests that patients who receive therapeutic antibodies after an extended period without treatment may be at higher risk of hypersensitivity reactions than patients who received regularly scheduled treatment. It is not known if this will occur with TYSABRI (see WARNINGS, Hypersensitivity and ADVERSE REACTIONS, Infusion-related Reactions).
Immunogenicity data are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody-positivity in an assay may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to TYSABRI® with the incidence of antibodies to other products may be misleading.
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Re: Tysabri Antibodies

Postby HarryZ » Sat Sep 09, 2006 6:16 pm

Approximately 24% of TYSABRI®-treated multiple sclerosis patients experienced an infusion-related reaction, compared to 18% of placebo-treated patients.


I would ask the question as to what was in the Placebo to cause 18% of those patients to experience a reaction?!! Supposedly Placebo is only an inert substance that shouldn't cause anything. I've never heard of that high a percentage of patient experiencing a reaction to a non-medication during a trial.

Harry
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Re: Tysabri Antibodies

Postby leeeeeway » Sun Sep 10, 2006 10:33 am

MetsFan wrote:If the presence of persistent antibodies is suspected, antibody testing should be performed. Antibodies may be detected and confirmed with sequential serum antibody tests. Antibodies detected early in the treatment course (e.g., within the first 6 months) may be transient and disappear with continued dosing. Repeat testing at 3 months after the initial positive result is recommended in patients in whom antibodies are detected to confirm that antibodies are persistent. Prescribers should consider the overall benefits and risks of TYSABRI® in a patient with persistent antibodies.


3 things:
1. Thanks, I had forgotten/not realised this. Obviously I'm too emotionally invested in this tho trying hard not to be...

2. Harry Z is thinking along the same lines I am...exactly what did I have the reaction to? I'm not allergic to anything that I know of.

3. I'm a "she" tho you could never tell frm my name ;-)

Lee
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Re: Tysabri Antibodies

Postby HarryZ » Sun Sep 10, 2006 11:31 am

Lee,

2. Harry Z is thinking along the same lines I am...exactly what did I have the reaction to? I'm not allergic to anything that I know of.


My inference to this was the fact that 18% of the Tysabri trial patients who were taking the Placebo ended up with a reaction from a supposed inert substance!! That is extremely high which means that there may have been something more than just an inert substance or perhaps a huge "placebo" negative reaction.

In your case you don't have to be allergic to anything to get a reaction from this drug. If your system has created antibodies to Tysabri, that would be enough to cause what happened to you.

3. I'm a "she" tho you could never tell frm my name ;-)


Oops :oops:

Harry
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Postby amelia » Sun Sep 10, 2006 12:32 pm

But remember:
All drugs out there have these side effects
stomach upset
diarrhea
constipation
headache
etc.....
Maybe those having a reaction was reacting to something totally different than Tysabri
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Postby leeeeeway » Sun Sep 10, 2006 2:22 pm

I accused the nurse of mixing up my Tysabri with Draino...

I will talk to my neuro or probably her nurse Monday...and Harry, an 18% placebo effect seems very high to me too.

Lee

Harry are you in North America? If not then it's way, way past you bedtime...
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Postby HarryZ » Sun Sep 10, 2006 6:06 pm

Lee,

Harry are you in North America? If not then it's way, way past you bedtime...


Yes...I live in London, Ontario, Canada so it really wasn't that late :)

Harry
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Postby HarryZ » Sun Sep 10, 2006 6:10 pm

Amelia,

amelia wrote:But remember:
All drugs out there have these side effects
stomach upset
diarrhea
constipation
headache
etc.....
Maybe those having a reaction was reacting to something totally different than Tysabri


When 18% are listed as having an adverse reaction, that would be to the Placebo because the reaction would take place within 2 hours of the infusion. And I'm sure that the patients would have been asked if they had taken any other drug. In trials they have to indicate this to the people conducting the trial. I'm still scratching my head on that high level!!

Harry
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Postby leeeeeway » Tue Sep 12, 2006 10:57 am

I meant to thank Metsfan and to say that I am giving a copy of what you sent in response to Amelia's question to my neuro. She may think it's Biogen hype. Let's see.

I spoke with my neuro's nurse yesterday and apparently what the good dr heard was not greatly in my favor...it will take 2 wks for the blood test to come back (!). I will see the dr then to get the results and make a decision...

I will post when I know something else...
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Postby amelia » Tue Sep 26, 2006 7:52 am

Lee,
Has there been any updates on your reaction to Tysabri?
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Postby leeeeeway » Wed Sep 27, 2006 3:46 pm

Thanks for asking, Amelia...as it turns out I just got off the phone with the nurse and to say I'm appalled would be an understatement. I have the "persistant" antibodies associated natalizumab and am therefore no longer a candidate for Tysabri. Further, everyone in that office who has had a reaction had doses in 2005 and then paused for 18 months which according to the insert is a feature of monoclonal antibodies or Remicade, anyway. So perhaps the delay did me in...I'm too upset to care at the moment. You have to be careful what you wish for cuz you might just get it.

Lee
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Postby amelia » Wed Sep 27, 2006 3:57 pm

I'm so sorry for you. It would be interesting to know more about the delayed infusions and antibodies
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