Tysabri Journal

[Jack2013]

Hello everyone, new here! Here is my background...

Im 20 years old (sophomore in college) and have had crohn's for 10 years. All the anti-TNF drugs stopped working (humira, cimzia, remicade, etc) and the summer before I began college I had an ileostomy for 3 months. I had the reversal before school began but as a freshman had somewhere between 6-8 outpatient surgeries to drain abscesses. This past summer I was given another ileostomy hoping everything in the rectal area would clear up, but it hasn't. Pretty much I have a huge rectal "cavity" that keeps filling up with pus. I have a very complex fistula tract that goes up to my tailbone. Last week I had the cavity drained and a malecot catheter was placed (because the seton rings were not effective enough). I also just started taking Cipro.

On January 2nd I had my first tysabri infusion (I tested negative for JC Virus). Taking tysabri is definitely worth the risk to me because it's either this or a permanent bag pretty much, and I hate the idea of that (especially since im only 20 y/o and in college). So far I havent noticed any difference in energy or pain, but I have noticed that my ileostomy output is the thickest it's ever been these past 2 weeks, so hopefully this is a sign for good things to come. I read that most patients don't feel significant effects until there 3rd or 4th infusion. I will try my best to update my progress with the tysabri to help other people who are considering taking this drug.

 

[xmdmom]

I just wanted to say hi and wish you well! I have a recently diagnosed 19 year old son, who is also a sophomore in college. Thank you for sharing your journaling your experience.

 

[kiny]

Good for you. I just wanted to say since I feel I have to, that in several places this drug is not approved for crohn's disease after it was taken off the market in those places. I don't know about the US but I know it was taken off the market at least once because quite a few people with crohn's disease lost their life on this drug.

I say this because I feel people need to know this and need to know both sides of the Tysabri story. This drug is no longer approved in many places around the world.

Good luck to you, hope you feel better.

 

[Jack2013]

^Thanks. Yeah, I chose the ileostomy over Tysabri 2 summers ago because the JC Virus wasn't out yet and I thought having a bag for 3 months would be the answer. But I feel the risk of PML (which is really small since im JCV negative) is worth it. If I were older and married I wouldn't hesitate to do a permanent ileostomy haha. Plus, there is a sister drug of Tysabri coming out this year that doesn't have the PML risk, so I should be switching to that after 6-8 infusions (which is good because the risk of PML is higher if on Tysabri for an extended amount of time).

 

[kiny]

I'm happy to hear you will be able to switch, they're hard decisions to make. Really glad to hear you can switch and maybe avoid more surgery.

 

[kh216]

Jack,
I hope that this treatment truly helps you. Please keep posting. Not many people are on Tysabri so your story will be a learning experience for all of us. Good luck to you.

 

[Mark in Seattle]

Jack, do you know the name of the sister drug of Tysabri?

 

[Jack2013]

Thanks everyone, and sorry I do not Mark but my doctor said it's coming out in 2013 and it doesn't cross the blood barrier in the brain (or something along those lines). If tysabri doesn't work for me I'm going to try Stelara, and if that also fails I think its gone with my rectum and the bag for me :/ anyone heard anything about Stelara?

 

[Mark in Seattle]

I'm guessing that this one may be the main one for Stelara (aka Ustekinumab):

http://www.ncbi.nlm.nih.gov/pubmed/23075178

Sandborn et. al seem to give it the thumbs up.

Apparently it targets IL-12 and 23 rather than TNF-alpha, at least that's my understanding based on my read of the abstract, but what do I know.

Couple other tidbits:

http://www.ncbi.nlm.nih.gov/pubmed/23147667

http://www.ncbi.nlm.nih.gov/pubmed/23121260

I threw in the hep B link because folks should be aware. My GI recently advised me based on bloodwork that I've never been successfully vaccinated against Hep B. So I inferred that I should get vaccinated; went to my primary care doc and set up the Hep B series.

I asked my GI specifically about Ustekinumab as a treatment option for me since I have no response to Humira, but he said Ustekinumab is not impressive from his standpoint. I didn't have the Sandborn study with me at the time to debate with him. He mentioned Tysabri as possibly my next option, but he wants to send me to surgery asap first. But now that you mention a sister to Tysabri, I'll have to look into that a bit more and possibly Ustkinumab.

Let's stay in touch....

 

[Mark in Seattle]

Is JC virus testing a solid approach we can rely on? Dunno....


http://www.ncbi.nlm.nih.gov/pubmed/23252596

Int J Neurosci. 2012 Dec 20. [Epub ahead of print]
A case of natalizumab-associated progressive multifocal leukoencephalopathy with repeated negative CSF JC virus testing.
Mazda ME, Brosch JR, Wiens AL, Bonnin J, Kamer AP, Mattson DH, Snook RJ.
SourceaIndiana University School of Medicine, Department of Neurology.

Abstract
ABSTRACT The development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab is a well-known potential risk. Diagnosis of PML can be confounded in patients with multiple sclerosis (MS) if new demyelinating lesions develop, and the sensitivity of existing diagnostic tests is less than ideal. In the case presented here, four samples of cerebrospinal fluid were negative for JC virus DNA by polymerase chain reaction, yet brain biopsy eventually proved positive by immunohistochemistry. A review of the limitations of existing clinical diagnostic tests is addressed, and we review the most recent literature on the proper management of natalizumab-treated MS patients.

 

[Mark in Seattle]

Jack, I wonder if your GI was referring to "Vedolizumab"

I came across this blurb from Mayo, which talks about Vedlizumab and a few others. I don't see the date this was mentioned, but Dr. Loftus Jr. seems to be indicating that this would be available 2013 or 2014.

Of selective adhesion molecule blockers currently in development, the most prominent is vedolizumab, a humanized monoclonal antibody to the adhesion molecule α4β7-integrin that theoretically inhibits leukocyte migration in the gut without affecting the blood-brain barrier. Vedolizumab has been studied for both Crohn's disease and UC.

In late February, drugmaker Takeda announced that vedolizumab had met all its primary endpoints in a pivotal phase 3 trial for ulcerative colitis. Trial results will be presented in detail at Digestive Disease Week 2012. To date, more than 1,000 patients have received the drug, with no known cases of PML.

"It's looking good in terms of safety, but we're waiting for the results of the big trials," Dr. Loftus says. "Vedolizumab might be a year-and-a-half to two years away from release."





A couple other meds mentioned on that link are:

Etrolizumab
GSK-1605786 (I think my GI might be trialing this; if so, he wasn't too keen on it).

Besides these, there are a couple others mentioned, but they appear to pertain to UC only.

 

[Mark in Seattle]

Sorry, one other link - these may not be relevant, but here they are:

Alequel
Teduglutide
Traficet-EN (CCX282)

http://ibdcrohns.about.com/od/prescriptiondrugs/a/ibdpipe.htm

 

[Jack2013]

Thank you for sharing all of your research, I will stay in touch. I think you are right that Vedolizamub is the sister drug my GI was referring too. I had my hep B tested last year at the student health center at school and it was all good. It sounds like there is still a little hope with the Stelara since it targets a different area, so if Tysabri proves to be ineffective I don't have to go straight to a permanent ileostomy. I really want to save my rectum! haha.

 

[Mark in Seattle]

I hear you brother! Fingers crossed for saving the rectum my friend!

 

[Mark in Seattle]

Updating the list a bit as per this writeup I came acrosss from Sandborn:


Dig Dis. 2012;30 Suppl 3:140-4. doi: 10.1159/000342742. Epub 2013 Jan 3.
The future of inflammatory bowel disease therapy: where do we go from here?.
Sandborn WJ.
Source Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, Calif., USA.

Abstract
There are six important trends that will impact the future of inflammatory bowel disease therapy. (1) Increased use of the biomarkers C-reactive protein (CRP) and fecal calprotectin, and increased imaging with colonoscopy and MRI enterography. (2) Increased use of pharmacokinetics to customize drug dosing for individual patients. Multiple factors impact the pharmacokinetics of monoclonal antibodies including the presence of antidrug antibodies, concomitant immunosuppression and low serum albumin and high CRP concentrations. (3) Evolution of treatment end points from symptoms to deep remission (a combination of both clinical remission and mucosal healing) to the prevention of bowel damage (in Crohn's disease) and surgery in the short-to-intermediate term and prevention of disability in the longer term. (4) Evolving data demonstrate that azathioprine monotherapy is minimally effective as a disease modification agent in Crohn's disease. Use of azathioprine as a monotherapy will decline. (5) Combination therapy with azathioprine and infliximab is superior to monotherapy with either agent. Use of combination therapy will increase. (6) There is a rich pipeline of novel therapeutic agents. Treatment strategies that appear particularly appealing include selective anti-integrin therapy with vedolizumab (anti-α4β7), etrolizumab (anti-β7 antibody) and PF-00547,659 (anti-MAdCAM-1 antibody), anti-interleukin 12/23p40 therapy with ustekinumab and Janus kinase 1, 2 and 3 inhibition with toafacitinib.
Copyright © 2012 S. Karger AG, Basel.

PMID:23295705[PubMed - in process]

 

[Jack2013]

Thank you for the information. Do you know when etrolizumab will be available for trial or just in general? The reason I really want to hold off on this ileostomy is because it sounds like so many medicines have been coming out each year, and I do not want to commit to something for life that could've been avoided by holding out one more year.

Statistically it looks like about 1/3 respond to Tysabri, and 1/3 to Stelara...hopefully I get lucky! I wish there was more information on how effectively these medicines treat rectal abscesses and fistulas. Just got to wait and see I guess.

 

[Mark in Seattle]

Sorry Jack, I'm not familiar with that one, but from what I see, poking around on the web a bit, it looks to me like this one is intended for UC. Print out the whole list and ask your doc. Or poke around and call or email the researchers or perhaps contact the pharma companies and inquire with them.


http://gut.bmj.com/content/early/2012/06/19/gutjnl-2011-301769.short?rss=1

Abstract
Objective Etrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.

 

[Jack2013]

Infusion #2 on Tuesday, hopefully this one gives me a bit more energy! I'll let everyone know how it goes.

 

[Jack2013]

So they said that they need the tysabri authorized by the aetna specialty pharmacy, so now my infusion is being pushed back. Pretty frustrating. Since I'm at college I had the change locations and the process has taken two weeks. If I cant get the infusion done tomorrow I will have to wait another week because I have a huge midterm coming up next monday that I need to study for, and the tysabri makes you tired for a day or two, so it would cut into study time. I'll keep everyone posted.

 

[Jack2013]

Had my second infusion today. Pretty uneventful. The usual hour for infusion and an hour of observation afterwards. Feeling a bit fatigued like last time but thats about it. The time between the 2 infusions a gained a tiny bit of energy (i repeat tiny, haha) and my ileostomy output continues to be much thicker. Still have a lot of rectal pain because of fistula tract and rectal cavity, and am taking Norco about three times a day for pain. Hopefully I get a bit more energy this time around and the 3rd and 4th infusions (where most people notice the most improvement) helps with the pain.

 

[Jack2013]

Good news. I went to see my surgeon yesterday because my bottom has been in a lot of pain the past week and I felt a lump around the drain. I thought I was going to need another surgery to drain an abscess and thought my overall health was worse, but he felt the site and actually thought it looked a lot better and softer! We realized that the abscess (which is in it's early stage) may have formed this past week because thats when I stopped taking cipro. He put me back on it and thinks that that could possibly take care of it on its own.

I think I may be seeing some early benefits of Tysabri because I have taken Cipro and Flagyl before and have had many seton rings to drain (this is my first malecot catheter which is a lot larger) and nothing ever happened. So the Tysabri must be doing something I would think. These next two infusions will be HUGE, I am both nervous and excited at the same time!

 

[kh216]

Hope these infusions will truly help you, Jack. You have really suffered more than your share from this dreadful disease.

 

[Jack2013]

Infusion #3 this Thursday, I still have rectal pain and it hurts to sit a lot. Taking Norco and taking daily baths. The actual area butt area actually feels pretty soft except for one area though, and my energy isn't terrible. Infusions 3 and 4 are the infusions that usually let you know if the medicine works, so I'll keep my fingers crossed

 

[Jack2013]

3rd infusion was today. Same old, same old. Not really anything to report, this time they asked me if I had noticed a loss in sight or balance (indication of PML) but I haven't at all. I assume if I feel a reaction from this infusion, it won't be for a few days. I'll keep everyone posted.

 

[Jack2013]

I did labs a few days after my third infusion and got them emailed to me today. My sed rate is only 7, which is the lowest it's been in a while. On the other hand my C-Reactive protein is 1.18 and the average range is below .80. What does it mean to have a normal sed rate but high CRP?

 

[Jack2013]

Had my 4th infusion yesterday, I've been feeling a bit better lately. I had a checkup with my GI last week and she said it was really good how my CRP dropped from 3.10 to 1.18. Meaning the infection/cavity/fistula tract could be healing a bit. Said the site felt better and that the pain im feeling now could mostly due to the malecot drain I have had for 5 months now.

 

[newlymarriedtocrohns]

Thank you so much for sharing your experience with Tysabri, Jack. My husband just started his first infusion with Tysabri this week, so it's very useful to hear how long it might take for it to kick in and work.

Fingers crossed that something new might help. Hope for the best for you too!

 

[Jack2013]

Its been a long time since I posted. I am having my 6th infusion this Friday. I had a pretty big surgery because my small intestine twisted randomly, so everything was pushed back 6 weeks. I was starting to do pretty well until then, but now I have been experience constant rectal pain again. When I visited my surgeon he still thought the rectal area looked much better and that the skin was a lot softer, so hopefully it could just be the malecot drain irritating me. I have been leaking still through the area and its often pretty bloody on the pads I wear. I hope getting into the routine of the infusions again gets me back on track.

 

[kh216]

Wow, you have been through a lot. Hope you feel better soon. It seemed like you were improving before the surgery. Hopefully, you will start to feel better as you continue to recover from the surgery.

 

[Jack2013]

Infusion #8 tomorrow. Im now enrolled in a CC, taking a medical leave from my 4 year (UCSB) and staying home. I had an MRI and my infected rectal area has cleared up a decent amount, but its unknown as to whether thats because of my malecot drain or the tysabri. the drain has really irritated me recently because a lot of granulation tissue has developed. Surgeon has burnt some off hoping to relieve the pain, but it looks like he will have to remove drain because I only feel relief for a few days and then pain comes back whenever I put pressure on my butt.

So the true test to see if tysabri is working is to see how I do without a drain, if I get an abscess like I was getting every 1-2 months before then I may discontinue. Oh, and I had my labs done and I'm still JC Virus negative which is good

 

[Jack2013]

So I got the infusion today and was just another typical infusion. Went to surgeon after and he removed the drain in the office. I feel quite a bit of relief now, hoping that the tysabri can prevent the fistula from worsening and keep away the abscesses! we shall see.

 

[Jack2013]

So after just 2 weeks of getting my drain pulled, I feel a perianal abscess coming back in its early stages surgeon talking to me about stem cell trial where they take fat from my abdominal wall and try to heal my complex fistula. looks like Tysabri hasn't been the answer for me.

 

[Lisa]

That stinks...hope they are able to figure out another treatment for you that works!!! How are any of your other symptoms, or is it just the fistula that is causing havoc?

 

[Jack2013]

That stinks...hope they are able to figure out another treatment for you that works!!! How are any of your other symptoms, or is it just the fistula that is causing havoc?

thanks its all from the fistula, its causing my rectum to be all messed up. I only have a very small piece of large intestine and my small intestine hasn't been a problem at all. hoping I can save my rectum and reverse this thing!

 

[Jenlarubia]

Hi Jack, I was hoping that you might be willing to talk to me a little bit about the Tysabri. My Gi referred me to a specialist who suggested I get tested for JC and go from there. I have tried all the other anti-TNF/biologics and am at a dead-end with my treatment. Im 34 and have had crohn's for 18 years. 3 resections and 3 fistulas and every med known to mankind. Please let me know if you don't mind talking a bit. I'd like to pick your brain a little. Thank you!