Several months have passed since I began taking Gilenya on May 5. Today I’m focusing on the drug’s possible side effects and how I have personally been affected. The good news is that I seem to be mostly fine so far. In spite of this year’s gloomy start with 2 separate attacks within it’s first few months, I have had no attacks since beginning this treatment. In hindsight I really do feel that Rebif, and probably interferons in general, are truly just not right for my body.

With my Gilenya followup appointment looming in a couple of weeks, I’ll soon find out if Gilenya suits me in the long run. As you can see, I do have my fingers crossed!

There are some known serious side effects of Gilenya and probably some yet to be discovered. Nothing is yet known about the effect of Gilenya use during pregnancy. We do know that the following side effects are possible :

• slowed heartrate for up to 1 month after beginning treatment
• decreased lymphocytes (white blood cells) leading to an increase in the risk of infections
• macular edema (swelling on or under the retina) – this primarily leads to blurry vision and blind spots (risk begins at 3 months)
• shortness of breath
• liver problems (or potential failure)
• high blood pressure

If you have read my other posts about MS, you have probably learned that Rebif affected my liver. After approximately 2.5 years of use, I ceased Rebif on the day my doctor let me see test results that showed liver enzymes in my blood were approximately 7x the acceptable limit for normal people. My neurologist considers this to be about 3x the acceptable limit for his patients with MS. This was the first time I was allowed to see test results and along with some other events this has convinced me I should always get copies of my test results to personally review. More on that in future posts.

Reviewing the list above, one would definitely have concerns. During the first few weeks, I could tell that my heart rate was slower, but it did normalize in about one month. So far, I’ve certainly noticed a slight change in my breath, but the change is very mild. Blood pressure is always high for me due to constant pain and muscle spasms – it has been controlled for the last 2 years and has not changed with this new medication. My optometrist has cleared me, for the moment, of any signs of macular edema. And finally, last week I had the necessary blood tests done to check my liver enzymes, my lymphocyte count, and various other stats that seem irrelevant to me. I will learn the results in 2 about 2 weeks.

Having recently joined Facebook, I am part of the Gilenya (Fingolimod) Users Support Group. I heartily recommend this to new and potential users. The discussion is largely about side effects, tips, etc. Learning that I am not alone in a few changes I experienced after starting usage, I want to add a couple of unofficial side effects to the list above based on my experience with Gilenya.

• Insomnia – For the first couple of months after beginning Gilenya, I only slept for about 3 to 4 hours per night, even with the futile use of Ambien. I can say with certainty now that I have not had insomnia for weeks, and my sleep has never been better. Before my diagnosis I seemed to always have insomnia. On interferon my sleep was often interrupted by the flu-like symptoms that tend to occur for most of us for several hours following a dose.  On Gilenya, having survived the initial insomnia, I usually sleep like a baby. This seems very common among other users – many of which began taking Gilenya in the morning rather than at night and used Sleepytime Tea by Celestial Seasonings to lull them into unconsciousness.
• Changes To The Skin – My skin has been brutally dry since the first week of treatment. Many others seem to experience this, but others have developed acne instead. Personally I may buy stock in the wonderful and expensive moisturizer I’ve started using to combat my issue. Regarding those who have acne instead – I wish you luck. I never figured that out in my teens and I doubt I could now.
• Increased Muscle And Nerve Pain – My spasticity and flexibility have noticeably  worsened, and it seems that others have also noticed this. Generally speaking, I am in more pain on a daily basis. Some patients take the drug at night to attempt to sleep through this.

Combined with work stress, this issue with spasticity and flexibility has kickstarted a yoga habit for my husband and myself. We aspire to work up to a daily routine (we use DVDs at home – we will never have time to fit classes into our irregular schedules). Doing yoga more frequently opened our eyes to the fact that our yoga equipment sucked. Having paper-thin mats on hardwood floors meant painful ankles and backs and an inability to complete all the poses. Poor straps and blocks meant we really weren’t using them. So we have officially overhauled our yoga gear and are loving the new stuff. This is now our current setup :

• Aurorae Northern Lights Yoga Mats
• GOGO Yoga Mat Harness
• Hugger Mugger Bamboo Yoga Block
• Yoga Strap With End Loops

This is certainly not the best gear for everyone, but it’s the best we’ve found for us. While I may not bend quite like the folks on the TV screen, I can now dwell on this in contorted positions while being in less pain than before. And that is fantastic.

For my readers who are contemplating what treatment to begin or who are not interested in Gilenya, I have discovered a valuable resource. The MSAA (The Multiple Sclerosis Association Of America) has developed a program to assist with choosing the best treatment for you from all available options. This program is called S.E.A.R.C.H. – http://www.msassociation.org/programs/search/ This looks like a great service for someone making a change in treatment and for those who are newly diagnosed. Considering the wealth of new drugs and their varied risks working their way through the FDA pipeline, I believe this will soon be even more useful than it is now.

In two weeks, if my test results prevent my continued use of Gilenya I may even need it for my next step forward. For now – I’m just hopeful.

Today I received my first phone call from Gilenya / Novartis, one month and three days after submitting forms to them. Nurses are specifically assigned as case managers to patients and stay with them at least through the process of getting started on the drug.

The call mostly consisted of me answering questions about my health history and current doctors. How long have I been diagnosed with Multiple Sclerosis, have I had recent vaccinations, etc. We went over the tests I would need to complete before the first dose, and she told me that they were still undergoing a “benefits investigation” to determine if I was eligible to receive the drug.

The nurse was extremely nice and sounded knowledgable, at least pertinent to the contents of the conversation. I wish I’d had the forethought to prepare any questions I might come up with ahead of time – I had begun to doubt that I would have any direct contact with the company again.

She did tell me a few things that I did not know before this call :

• There is a “two week rule” for Gilenya. If a person on Gilenya stops using the drug for two weeks, that person is required to undergo the entire approval process again to restart it – vision tests, EKG, blood tests galore, monitored doses in a doc office, etc…
• Although Will and I don’t intend to have children, it will probably interest anyone who is thinking of starting the drug that if a pregnancy occurs while on Gilenya / Fingolimod there is a registry they want you to join so that they can follow your progress. (PS – You should really try to NOT get pregnant on it)
• Any vaccinations must be cleared with a neurologist to ensure that no live virus vaccinations are administered (viral infections usually trigger MS attacks).

Finally, I have permission to contact Gilenya / Novartis and proceed with all the tests necessary to start the drug.

Pâté

There is some good news in my quest to start Gilenya – and it really is starting to feel like I’m seeking the holy grail. On the day I ceased Rebif I also saw a gastroenterologist for my elevated liver enzymes. The tally so far is $800 for the consult, $600 for the results, and forthcoming bills for some blood tests and an abdomenal ultrasound. Results are that I am clear of all liver diseases – he seemed disappointed.

In hindsight, I should have just waited to see the GI. After almost a month of being off Rebif, new blood tests reveal that my liver function is almost back to normal. Previous tests actually showed my enzymes at about 6 to 7 times the high limit for normal, which was worse than I had known. Now I am only a few points out of bounds. Time should take care of the rest.

A lot of relief came with this news. Also, I can’t stress enough the lack of stress that comes with knowing that I don’t have to take a shot every other day. So, now that my liver is suitable for sustaining human life again I’m hoping that I also won’t have to switch to the daily Copaxone injection.

Unfortunately, all that I’ve heard from Gilenya is that they would have someone return my call about a week ago. Which hasn’t happened. However, apparently they have been calling my doctor. So, while they won’t speak to me (the patient), I have heard through the grapevine that they are in the process of negotiating with my insurance company. Perhaps this is why the insurance company has started sending me packets notifying me that they have assigned an advocate for my “complex health issues.” While I appreciate the advocate, it does sting a bit that the insurance company has to hire nurses to fight them for my healthcare.

My optometrist completed all necessary vision tests last week. My neurologist has ordered some additional blood tests and an EKG. Then I will plan to spend 2 days in his office to be monitored for my first 2 doses in April, assuming that insurance approval has completed. The process must be difficult for everyone involved — my neurologist’s office staff look as though their blood pressure skyrockets every time “Fingolimod” is uttered. However, finally, everything looks to be in order. Unless, of course, you consider that no one at Novartis seems willing to speak to me (actually, I was sent a mailer today with their phone number if that counts).

Their general silence has begun to shatter my confidence in the drug. Are they just overwhelmed and have no time for new orders? Have they just hired employees who are still getting used to the process (of using a phone?)? Or, more importantly, are they intentionally slowing Gilenya’s introduction to the market for fear of discovering new side effects or higher occurrences of known side effects?

Let’s hope they’re just overrun with orders. Optimism remains… for now….

Tick Tock, Gilenya, Tick Tock

Almost two weeks ago I posted that  I was in the process of switching to Gilenya. Not so fast, I suppose. My neurologist’s office staff was eager for me to let Gilenya set up all of my doctor appointments for me to undergo the necessary tests. By their accounts they faxed in my information the morning I was in their office, and then a few days later when they hadn’t heard anything back. And then again when I called them after a very unproductive phone call with Gilenya.

Several months ago I switched positions within the company to work in a 24/7 network surveillance group. We rotate weekends, leaving me with a “weekend” during the week for a month here and there. I had hoped that I could use these days to get through all of my doctor appointments this month. But the opportunity to accomplish that is rapidly vanishing.

When I gave up on hearing from Gilenya, I called them. I was not in their system and was told either the doctor had not sent anything or that it can take a couple of weeks for someone to process the fax from my doctor. The representatives also advised me that I should just setup all appointments with doctors and for tests myself as it would take a long time if I relied on them to do it. They then told me that they also would not order the tests, that my neurologist had to do that anyway.

At this point, I wanted to cut Gilenya-The-Company out of the process of getting to Gilenya-The-Drug. I called my neurologist and asked them to help order the tests from my primary care physician so that I could get started without waiting for Gilenya. This is when I discovered that they rely on Gilenya to negotiate approval with my insurance company.

So, with no tests ordered and no response from Gilenya I am simply waiting to see what happens.

There’s no denying the dual frustration of having to wait for faceless others somewhere to get around to my file while I effectively become unprotected by any DMD having already stopped interferon treatment. Hopefully my next post will be good news rather than more of nothing.

Gilenya (Fingolimod)

As it turns out, similarly to my father’s results with Avonex, Rebif has caused my liver enzymes to shoot up to about 3X the upper limit of normal in the span of slightly less than 2 years. My options?

1) Tysabri : the risk of PML is too severe for me to brave this drug – reputed to be a risk of death or severe disability as high as 1 in 200 for some individuals and 1 in 2000 for others
2) Copaxone : statistically slightly less effective than interferons – works great for my father but I truly don’t want to do a daily injection except as a last resort
3) Gilenya : aka Fingolimod – when this was first approved by the FDA I wrote a blog post to summarize all the information I could find – it is the only oral disease modifying drug for multiple sclerosis – DING! DING! DING!

I have chosen to switch to Gilenya.

My neurologist says I will be his third patient to begin the process. In order to be approved I have to go through a handful of doctor appointments. The process reminds me a little of Scott Pilgrim vs. The World and so far has involved about the same volume of blood. I’ve seen a GI for my liver enzymes and he has put me through a round of blood tests and is checking for tumors just to be certain that the interferon was the sole cause of elevated enzymes. My optometrist will have to check a few more things than in a typical exam. My heart will need to be evaluated due to the risk of heart issues during the first dose. Saving the best for last – I have to lower my liver enzymes before starting the drug by ceasing interferon (no more shots!). The first time I take Gilenya I will have to spend the day in my neurologist’s office — if my heart rate drops I have to run in place to bring it up.

My father tells me that I will feel fantastic after I have stopped taking interferon for a couple of weeks. This is believable for several reasons – a fully functioning liver is probably a good thing, having interferon and its resulting flu symptoms out of my system is bound to be great, and my relief at the moment my neurologist told me to stop the injections made me realize how stressful the constant looming injections have been.

There are more risks with Gilenya than with the interferons and Copaxone, but I think I will fare pretty well. If I develop macular edema (0.4% chance), it may be possible to reverse. Other significant and potentially life-threatening problems can result from cold sores (I don’t get them) and chicken pox (had it when I was 12).

It certainly isn’t completely safe, and it can raise my liver enzymes as well. If it does, hello Copaxone. In the meantime I am extremely optimistic even if everyone else seems apprehensive. The most recent edition of Momentum magazine outlines all the MS drugs currently in the pipeline. Some sound great, some sound dubious. Having traveled once with prefilled syringes, I hope that this medicine will work out and I won’t have to do that again. This isn’t all about convenience and pain, but there’s no denying that it plays a large part in the decision.

Having had an exacerbation a few weeks ago, followed by Solumedrol infusions and an MRI the next day, I do wonder if I’m as responsive to interferon as others might be. No drug will prevent all attacks, but it’s possible that Gilenya could be more effective for me than Rebif. If all goes well, and especially if all goes terribly, I’ll try to chronicle how things progress with Gilenya here on the blog for anyone who may be considering it. Certainly, anyone would prefer more research and anecdotal information before committing to a drug like this. But my liver says it’s time to switch and it really is one of those important organs. Wish me well!

UPDATE

Since this post I have fought my way through the insurance and approval battle and have begun the medication. Please feel free to see my additional posts regarding this.

Gilenya (fingolimod) By Novartis

This post is a little late, but there has been a huge breakthrough in MS treatment. An oral medication by Novartis, Gilenya (formerly fingolimod and FTY720), has finally been approved by the FDA to be available by prescription as a daily 0.5 mg capsule as a first line treatment in October.

It is an immunomodulatory drug called an S1P-receptor modulator, similar to cell surface receptors on white blood cells. The drug was initially created to prevent tissue rejection following kidney transplants, but the dosage required for success was so high as to be toxic. The recommended dose for MS treatment is 5 times lower than in this initial attempt.

Essentially, this drug strips out a chemical component forcing T cells to stay in the lymph nodes where they cannot attack the central nervous system. It may also enhance repair to damaged neurons, have neuroprotective effects, and reduce whole-brain atrophy. Most treatments for MS now reduce relapses by an average of 35%. A study of Gilenya suggests a 60% reduction in relapse rate and a 74% to 82% reduction in damage as measured by MRI.

The downside to this is that there are some possible adverse side effects such as headache, flu, diarrhea, back pain, abnormal liver tests and cough. The worst possibilities are a reduction in heart rate, infrequent transient AV conduction block of the heart, increases in blood pressure; macular edema, elevated liver enzymes; and increased infections such as bronchitis and herpes. No one knows the effect of the drug on pregnancy or breastfeeding, so contraception is suggested while taking this drug. Studies so far have suggested that white blood cells return to their normal rates approximately 2 months after cessation of the drug.

Prior to starting the drug, patients need to be evaluated for baseline data on the heart, lungs, liver, eyes and vision, blood pressure, pulse, and white-blood-cell count. Patients should not take the drug if they have recently been infected by or vaccinated against chicken pox. You should be monitored for a reduction in heart rate and other side effects for 6 hours at a medical facility after your first dose

The price for Gilenya is higher than that of existing medications – $48,000 annually. Most existing treatments max out at about $38,000 annually.

When I started researching all the available data about Gilenya to write this article I was frustrated by 2 things :

• It is virtually impossible to find all the pertinent information in any one location
• Gilenya will probably still have an adverse effect on my liver.

As it stands, I suppose if and when I go off of Rebif it will probably be to Copaxone, but I would love to give this drug a try.  Enough of the facts — I’m just so excited about this – the more treatment options we have available the closer we are to a cure!

Tysabri : A picture is worth $6900!

My parents assured me that although they’ve gone to many MS events they had never been to a spectacle like this before.

Last night I trekked down to the basement of a branch of the AnMed hospital in Anderson, SC to attend an MS event my parents had alerted me to called Dialogue of Hope and Health. I can’t deny that I was hoping that the “hope” in the title of the event referred to the new oral medications soon to be available (at least in other countries) or perhaps stem cell developments. It turned out to be something between a sales pitch and damage control conducted by a local neurologist and a Tysabri sales rep.

In my opinion, it is a questionable ethical choice for a neurologist to invite his patients to a deceptively named seminar to be pitched to by a drug rep with only negative statements about alternatives and without providing a forum for the other MS DMD manufacturers to respond to allegations leveraged by the doctor and rep or to the questions posed by the attendees.

Tysabri is a relatively new drug, and I doubt my neurologist has more than a few patients on it. This neurologist does not specialize in MS but still drew what appeared to be at least 40 Medicare patients all on Tysabri out on a Wednesday night to wander around a hospital until they found the basement conference room. He said he organized the meeting (I wasn’t aware he had organized it until it had started) to eliminate some questions floating around. In other words, to get his Medicare patients to shut up about taking “medication holidays” and switching from Tysabri.

When we showed up, we were asked to fill out additional paperwork for government records. This raises another question – did taxpayer money go to fund this virtual sales pitch? It seems as though this doctor just got Tysabri to put together a thing for all his medicare patients so he could get them in a room together and tell them there is no hope on any drug other than Tysabri.

The meeting started with him saying no one can tell you what drug to take, but the message that followed was very different. Essentially, the message was that interferons and betaseron are bad and don’t work and that the new oral drugs (Cladribine and Fingolimod) kill you with cancer and infections. That marijuana has no effect on MS symptoms and that people just like to get high. We were all but promised that people don’t die from PML and that MS patients no longer have any attacks once they’re on Tysabri.

Following the doctor/patient bullying session, the sales rep came over to give me his expert medical advice. The whole event left me seething. If I decide to take the risk and go on Tysabri it isn’t going to be the result of the 3 questionable men running the show last night. PML is a scary thing and no one should be mocked for fearing it. The statistics presented last night (if you can trust them) are that only about 1/4 of people on Tysabri who develop PML will die from it, but the rest will be left with permanent disability ranging from mild to the need for life support. 1/1000 Tysabri users will develop PML and your chance of developing it increases with use.

None of our options for Disease Modifying Drugs are great. They all have drawbacks. Rebif is only supposed to reduce my relapses by 30% and no one can say what the last 18 months would have been like if I had not been on it. I have less options for neurologists than if I lived in a more metropolitan area, but I now know another doctor that has made it to my never in a million years list.

I understand that pharmaceutical companies are businesses expecting to make money. Sometimes they fail spectacularly in creating a drug and future drug prices make up for it. Sometimes they are spectacularly successful, but it is still incredibly expensive to develop the drug and prices are affected by that. Even so, when Rebif representatives call me they want to know how my health is. They don’t want me to die from liver failure just so that they can sell more Rebif.

I have nothing against Tysabri. I may even have to switch to it soon.

I have been on Rebif for over a year, but I’ve had several attacks (although I don’t think I’ve had any new lesions). According to the sales reps there, Tysabri doesn’t help prevent MS attacks following viral infections, although he was adamant that if I had an MS attack for any reason on Rebif that it’s not controlled and I should switch to Tysabri. With Rebif, sometimes the injection pain is terrible and sometimes I hardly feel it. The real issue at hand is liver function. I’m borderline and monitoring this is becoming increasingly difficult.

As of 2010 my insurance company, Cigna, has decided that blood tests ordered by a neurologist do not follow normal coverage guidelines and must come out of my deductible. Therefore, one simple blood test for liver function cost me nearly $400. I’m not sure I know anyone who is willing to spend $1600 a year on blood tests if they can avoid it. There were years in college when that’s all I spent on rent!

If my liver function deteriorates and I decide to shell out another $400 to find this out, then my options are Copaxone and Tysabri. After last night, I’m leaning toward Copaxone, daily injections and all.

Interferon injections are more than unpleasant.

I am so glad I make a habit of reading BBC News daily as US news agencies frequently skim over important things in favor of the shocking or violent. Today they published a story about new oral multiple sclerosis treatments that are likely to be available in England in 2011. As someone whose liver does not particularly like Interferon and is afraid of the risk of death from Tysabri infusions this might be a godsend. Since interferons are not available as generics (they contain living organisms and are exempt from status that would let them ever become generic) this could open inexpensive and more successful treatment options to a host of people who have no option but to live with the effects of the disease untreated. The full article and link to it are pasted below, but here is the basic information you want:

• The oral drugs in question are Fingolimod and Cladribine
• The drugs are considerably more effective at reducing relapses than current available treatments
• The drugs may increase your chances of herpes and cancer

Trials spark hope of pill for MS

Oral drugs to treat multiple sclerosis could become available in 2011 after promising results in two trials.

Drug licences have been applied for and the MS Society said it was “great news” for people with MS – current treatments involve injections or infusions.

The trials of the drugs each involved 1,000 people in over 18 countries, the New England Journal of Medicine says.

Cladribine and Fingolimod, which come as tablets, cut relapse rates by 50-60% over two years compared with placebos.

Fingolimod was also tested against the widely used injection, beta interferon 1a. The trial showed the new drug was twice as effective in reducing the number of relapses over a year.

“ The evidence is now there and we will be working with the relevant authorities to make sure those who will benefit can get access ”

- Dr Doug Brown, Biomedical Research Manager at the MS Society