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**Suebee** · 09-14-2015, 02:24 PM

Tysabri and rebound flare after stopping med?

Apollo, thanks for summarizing tysabri. I appreciate it. I am on copaxone but I try to keep abreast of other options. You're obviously passionate about this dMD. Do you or a close one take tysabri? I am interested in hearing more about what made this dmd right for your particular situation. Other ms blogs have pointed out that it if one does need to stop tysabri after 2 yrs when the risk of PML increases it can cause a flare or worsening of symptoms. Even if you start another dmd.! This is very frightening to me. I would like to know the percentage of patients that experience a worsening of symptoms after stopping tysabri and if they can ever get back to baseline. What did your doctor advice about the protcol for stopping tysabri if you need too? Suebee

**Apollo** · 09-15-2015, 11:51 AM

Response to medicine is individual; I could not advocate a particular medicine for a particular person. However, we can and should gather data from published, peer-reviewed scientific studies which demonstrate what a medicine does in terms of percentages of patients; so I listed some Tysabri studies.

�Other ms blogs have pointed out that it if one does need to stop tysabri after 2 yrs when the risk of PML increases it can cause a flare or worsening of symptoms.� First, there is no increase in the risk of PML after two years if you are JCV negative. But it is true, as you mentioned, if someone halts Tysabri for any reason there is risk of having a flare or worsening symptoms. Why?

Keep in mind what Tysabri is doing� blocking certain damaging cells from crossing the blood brain barrier. Tysabri isn�t killing those cells off, they are still circulating in the body. But remove the block (Tysabri) and those may (but not always) flood in and cause damage. I know that seems frightening but I wonder if the result is, in reality, any worse than never blocking them in the first place? Why wouldn�t the fear of damage w/o treatment be comparable to the fear of damage in stopping treatment?

I understand the fear you mention but to me it is illogical and irrational. For myself, I cannot in clear conscience embrace poor logic. I mean no disrespect at all, I fully support each person�s treatment decisions. We are all different. The damage w/o effective treatment should be an equally a legitimate fear, that�s all I�m saying.

Damage is occurring in RRMS sub-clinically much of the time, if not all of the time, occasionally peaking in relapse. Meds which reduce inflammation and relapses are helpful, IMO, with varying degrees of success. In MS, can we ever get back to baseline if the baseline is long enough? Again, getting back to baseline is another illogical line of reasoning relative to stopping any DMD, including Tysabri, IMHO.

Recent studies have demonstrated the best protocol for stopping Tysabri should be the shortest window possible before beginning another effective DMD, although many neuros are not early adopters, sorry to say. You want to make certain that someone does not have asymptomatic PML before starting a new DMD; some neuros do that by just having a patient wait for several months to make sure PML isn�t lurking under clinical expression. And, that period between when Tysabri effectiveness wears off and before the next med begins effectiveness is the time when MS can and often does rebound strongly. The longer the wait, the greater the risk of MS rebound because we are without DMD coverage.

The best neuros do a LP and test the CSF for JC virus. If there is no JC virus in the fluid there is virtually no chance of PML (remember JC virus alone causes PML). The patient can safely begin another med immediately, knowing there is no asymptomatic PML.

The shortest window between Tysabri and the next DMD is the safest but it must be done properly (LP). Many of the flares we have seen post-Tysabri could have been avoided if the neuro had been up to speed with current knowledge, IMO.

What made Tysabri the right med? Cold blooded calculations� superior percentages of effectiveness offer the best chance of a normal life, IMO. Fear can be a good thing but it can also keep us from the best. Gaining knowledge, making sober assessments, not caving to fear� these are certain to only help in making good treatment decisions. I recommend Ben Carson�s book (yep, the one running for President) Take the Risk.

Forgive me for any unintended harshness, won't you? Good luck, Sue!

**ActiveMSers** · 09-15-2015, 04:41 PM

Apollo, I appreciate your candor, but Suebee has a point, too. A rational and logical one. We're in this together. Let's keep it civil. Thanks.

**Apollo** · 09-15-2015, 08:26 PM

I apologize Sue. I truly did not intend to discount your viewpoint.

One of my tragic experiences was having someone close who was so fearful of PML that she stopped Tysabri even though she was JCV negative. She was in good health and doing fine, actually was doing great.

They waited too long to begin another med which doesn't work very well, anyway. The result was disastrous. Ultimately, she stopped that med and went back to Tysabri. Unfortunately, once significant neurological damage occurs it is very, difficult to repair.

Her life permanently changed for the worse. When we talked prior to her decision to halt Tysabri she asked my opinion but I didn't express it with conviction, not wanting to be uncivil, I guess. I believe my nice as pie generalities hurt her immensely in a very real way.

In any case, I understand apprehension with Tysabri and I meant no disrespect to you. I actually think you are a wonderful person. I hope I have not hurt your feelings; that was never my intention.

Probably best to take a break and sign-off. I don't want to conflict with anyone. Sayonara.

**Suebee** · 09-21-2015, 10:13 AM

Apollo, thank you for apology. I understand that it's easy to overstep in social media, no matter how well meaning. There is no Emily Post of the internet to guide us. And aLthough everyone here is anonymous (Cheeky or mythological monikers and telltale idioms aside), we are still real people, dealing with a real disease, and so very much at stake. Because we have this common identity, I'm guessing that is why strong Words of persuasion seem obvious and stand out here, like a shillaber at the circus. But I've really appreciated your other posts here because I lack a science background, and Ive benefited from summaries of medical journal articles you've posted.

I'm interested in Tysabri because it has been offered as an option to me. I haven't switched to it yet. I've approached the decision much like Julie Stachowiak, ( http://ms.about.com/od/treatments/a/...d-Pml-Risk.htm) Ph.D., an epidemiologist and person living with Ms. She writes,
"Given my current situation of pretty stable relapsing-remitting MS, I probably wouldn't take Tysabri if my JC virus antibody test came back positive. However, if Tysabri was the last therapy available to me and I was experiencing increasing disability, I would take a positive JV virus antibody test as just one piece in the whole equation and have some serious discussions with my neurologist (and my loved ones) about the situation. A careful risk-benefit analysis (with a healthy dose of emotion) would help me arrive at my answer."

And I do have additional questions about Tysabri, which some of your comments raised. Specifically, does one need blood or lumbar punctures every 6 months to monitor for JCV, since one can get exposed at anytime? How common are false negatives with blood tests? Is being on Tysabri greater than 2 years and having used immune suppressants considered risk factors for PML or not? I find It so difficult to sort through all the ms DMD information. And, just adding to my anxiety, A recent TED talk caused me some alarm as it explained how pharmaceutical companies can manipulate the facts and can even employ so called "AstroTurf" advocates to gain public support of certain drugs. https://www.youtube.com/watch?v=-bYAQ-ZZtEU
That really made my blood run cold. I wish the pharmaceutical industry wasn't like this. To be properly armed to fight ms, We have no choice but to trust in the integrity of the information supporting our treatment. Suebee

**Marinadca** · 09-21-2015, 08:02 PM

I just had my 4th Tysabri infusion, I made the change after almost 4 years on Gilenyia. Really I did not have " a lot" of progression, 2 small new lesions, but they popped up in the same MRI so I decided to give Tysabri a try. Technically it is my 3rd line treatment (I did copoxane for about a year before Gilenyia was approved.).

I am also JCV +, and very much so, so I will stay on this med for 2 years only. I am terrified of the rebound effect you mention Sue, but decided to go for it anyhow. We will see how it goes!

**Suebee** · 09-22-2015, 08:23 PM

Marinadca, thanks for sharing your personal situation. I understand why you switched. Tysabri offers a lot of hope. Thankfully, There seems to be a greater medical awareness on best method to stop and transition off it if one needs to now. I hope you are feeling in good health and that Tysabri is working well for you. I'll be interested on updates, if you want to share more. Best wishes, Suebee.

**Marinadca** · 09-23-2015, 04:59 PM

I will definitely checkin and share Suebee

From the beginning I really wanted to treat my MS aggressively, so that played heavily into my decision to switch.

I did not even consider possibly getting a LP to check for dormant PML, but I had an extremely poor experience with my diagnosing LP so I will most likely be going back to Gilenyia after the shortest time period permissible. My hope is that there will something new and more effective I can do by the time I am ready to come off.

Honestly, I notice no difference really. Maybe my cardio endurance is better? I am not really sure. But we will see when I get my next set of MRIs.

**Cvfactor** · 09-24-2015, 04:30 PM

I think looking for PML is not up to your doctor when you start Tysabri, it is an FDA mandate. Any doctor prescribing Tysabri has to have approval through the TOUCH program.

The purpose of the TOUCH program is to ensure you are monitored correctly and was put in place prior to Tysabri being re-introduced into the market after the initial deaths started occurring. Here is the FDA's website:

http://www.fda.gov/Drugs/DrugSafety/.../ucm199872.htm

**Cvfactor** · 09-24-2015, 04:51 PM

Suebee,

Here is a new article that discusses the issue of when to switch therapies:

http://www.sciencedirect.com/science...11034815001066

**Cvfactor** · 09-25-2015, 01:40 PM

One other thing I should mention is the concept of "protective autoimmunity" which is the notion that autoreactive immune cells can also provide a benefit. This theory makes sense to me since all people including healthy individuals have autoreactive immune cells. Here is an article that describes it:

http://m.nro.sagepub.com/content/ear...16799.abstract

I think when Tysabri was developed it was thought that the brain was an immune privileged organ meaning that immune cells were kept out by the blood-barrier, however it seems that immune cells do enter the CNS which is why PML is not a concern in healthy people, even those with the JC virus.

If protective autoimmunity is a real concept, this would explain why the authors could not find a consistent positive effect on brain atrophy for those on Tysabri in the paper I posted to Suebee above.

So I think Tysabri might be good at keeping immune cells out of the CNS and may be the answer for those with highly active disease, but in my opinion it is not clear what impact the mechanisms of action of Tysabri will have in the longterm.

**Suebee** · 09-25-2015, 02:08 PM

CVfactor, once again thank you for finding great sources that help explain the meds and how they are actually disease modifying. One can not make a truly educated decision about treatment without digging into some of this head spinning esoteric info. Shame on pharmaceutical companies for making it hard to sift through all the data. I agree with you about your analysis Tysabri. If I were to switch, I would want the serious conversation with neuro if the benefit outweighed the risks for my situation. I'm afraid, I may be in process of moving to spms. It's unclear rt now, time will answer. So I am trying to regain lost strenght, and understand the drugs I could switch to in this gray area status I'm in, and keep in the game. As always, I appreciate knowing your on my virtual team. Suebee

**Cvfactor** · 09-25-2015, 02:15 PM

Suebee,

Sorry to hear you think you are entering SPMS. Hopefully you and your doc can find a medication that will help.

Take care

**Cvfactor** · 09-28-2015, 06:52 AM

Rituximab

Hi Subee,

There is some news on a drug in development called Ocrelizumab. The initial communication from the company doing trials is that this drug has an impact on progressive MS as well as relapsing-remitting ms. Here is a link:

http://multiple-sclerosis-research.b...-news-for.html

This company is pursuing this drug because another drug (Rituximab) has a patent that expires this year. Both of these drugs are very similar and many MSers are taking Rituximab off-lablel.

I belong to a facebook page of people who are taking Rituximab and it may be worthwhile for you to ask questions.

https://www.facebook.com/groups/Rituxan4MS/

Good luck.

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