Bits and Pieces: Pharmaceutical Follies Edition

Oh, those pharmaceutical companies, always generating such tremendous tidings of joy and overwhelming warm and fuzzy feelings in the hearts of their adoring public. They’ve cured almost every disease that has ever plagued mankind, urged doctors to only prescribe their products when absolutely necessary, kept the price of medicine low enough so that even the most unfortunate can afford their wares, and have conducted their beneficent and altruistic research in a transparent, above the board manner that engenders absolute trust in all of their findings. How lucky we are to…

Whoops! Sorry, I started writing the above paragraph during a brief visit to an alternate universe, one much more to my liking, in which vintage Godzilla movies keep winning Oscars decades after they were made, bacon is a health food, blithering idiots are scorned rather than given their own reality TV shows, and I’m fluent in 10 languages, drive a mint condition 1956 Ford Thunderbird, and am a world-class triathlete. But, since I appear to have suddenly shifted back to this reality, I guess I’ll have to change the tenor of this blog post. Bummer.

I haven’t done a “Bits and Pieces” post in a while, because, well, it’s my blog and I’ll scribble what I want to. There’s been lots of stuff happening in the world of MS, and in the world in general, so in order to limit this post to a length not exceeding War and Peace, I’ll judiciously pick just which bits and pieces of info to highlight. Not that I’ve ever been willy-nilly about picking bits and pieces in previous posts, but I needed an excuse to use the expression willy-nilly, due to an obligation made in an alternate universe. We all must do our part to keep the cosmos in order, you know…

So, presented for your review are the following tidbits of mostly MS related news items, most of them having to do with pharmaceutical companies and their products, with a liberal dose of my take on things thrown in. Bon appétit…

♦ A study which throws into question the efficacy of the interferon drugs (Rebif, Avonex, and Betaseron) to alter the course of MS disease progression (click here) has caused quite a bit of hubbub on numerous Internet MS related forums, blogs, websites, and Facebook pages, and rightfully so. This retrospective study looked at three groups of MS patients, and tracked the course of their disease over a ten-year period. One group was comprised of patients who were treated with the interferon drugs, another of MS patients that were left untreated, and a third was comprised of patients from before the days that the interferon drugs were first made available (they arrived on the scene in the mid-1990s). The study found that patients treated with interferon were no less likely than untreated patients to experience disease progression leading to significant disability.

However, another study, which received much less play in the Internet MS universe, came to the exact opposite conclusion, finding that the interferon drugs do significantly reduce the risk of progression for multiple sclerosis patients across the board (click here).

So what’s going on here? Obviously, it’s hard to say, but, as this article points out (click here), the study that found the interferons ineffective had some possible methodological flaws. One might assume that the population of patients in the untreated group was left untreated because their disease was generally less severe and aggressive than those who were in the treated group, which would invalidate a direct comparison between these two patient populations. If this were the case, the study’s findings would actually show the interferons were effective, because they kept patients with more severe disease from progressing more quickly than those with less severe disease.

Whatever the case, the situation remains as clear as mud. The interferon drugs are much disparaged among many MS patients, because they obviously do not cure MS, cost a fortune, have very unpleasant side effects, don’t work at all for many who try them, and, to top it off, are injectables, and nobody relishes the idea of giving themselves a shot several times a week. What does seem clear, though, is that, at the very least, these drugs do offer some patients relief from debilitating relapses, even if they don’t ultimately alter the course of their disease. Many patients report a severe curtailing of their relapse rates once on the interferon drugs, which amounts to a significant uptick in their quality of life. This benefit cannot be discounted, even if interferons ultimately do prove to be worthless in stopping disease progression, which of course would be disappointing. I’m not one to defend the pharmaceutical companies, but the interferons were never approved under the auspices of stopping disease progression; rather, their approval was based on their ability to reduce relapse rates and the amount of enhancing lesions as seen on MRIs. It was hoped that these two effects would translate into a lessening of disease progression, but that was always just an assumption, a point never tested in clinical trials.

An interesting window into the opinions of patients about this issue is the comments that appear after a piece Julie Stachowiak wrote about the negative study in her always excellent Ask.com MS column (click here). I expected to see a fusillade of outrage voiced by the commenters, but surprisingly, a preponderance of the comments are from patients who say they’ve benefited from the interferons and intent to stay on them because of their increased quality of life. I guess the bottom line is that, drugs or no drugs, MS sucks, and will continue to suck for the foreseeable future. Actually, that’s pretty much the bottom line about everything related to MS…

♦ Here’s an example of a pharmaceutical company snatching victory from the jaws of defeat. The FDA recently warned about seizures associated with the MS drug Ampyra (click here), made by Acorda pharmaceuticals, which is supposed to improve the ability to walk in some MS patients. Much to the chagrin of investors, this warning caused a marked decrease in Acorda’s stock price. Ampyra is given in 10 mg doses, and the FDA asked Acorda to conduct trials to see if a 5 mg dose would be as effective as a 10 mg dose while cutting the risk of seizures.

The results of this follow-up study showed that both the 5 mg and 10 mg doses of Ampyra failed to demonstrate any efficacy in regards to increased walking ability (click here). Acorda claims that this is because the methodology used in this study was different than that of the original studies. Regardless, Ampyra remains on the market in 10 mg doses, since it was previously approved by the FDA based on prior clinical study results. In a happy twist for the drug company and its investors, even though the drug failed the follow-up study, the fact that the 5 mg dose was ineffective means that Acorda retains its long-term patent rights on the 10 mg dose, whereas if the 5 mg dose have been effective copycat drugs could have been manufactured and placed on the market as soon as 2017 (click here). Acorda’s stock price rose on this news, so all is well in investor land, despite the fact that the drug can cause seizures and may be largely ineffective. So, bad news for MS patients, good news for those making money through the marketing of a drug whose efficacy is highly suspect. Talk about alternate universes…

♦ In a case that didn’t work out quite as well for the drug company, Genzyme submitted the drug Lemtrada (formally known as Campath) to the FDA, fully expecting an approval. The company was so confident that the drug would be approved that they started pulling Campath, which had been marketed for years as a treatment for leukemia, off the shelves to keep it from being used off label to treat MS. This was done so that Genzyme could hike the price of the renamed drug to fully take advantage of the more lucrative multiple sclerosis market (click here). After all, MS patients need to take their drugs for years on end, but victims of leukemia either go into remission or die, limiting their necessity to consume drugs. But, ha ha on Genzyme, the FDA turned around and requested that the company resubmit their application (click here), asking the company to change the presentation of the data so the agency can “better navigate the application”, whatever that means. The FDA didn’t order any additional trials of studies to be run.

While it feels good to see a case of corporate greed smacked back, even if only a little, Lemtrada is an interesting MS drug. It is a powerful immunosuppressant, but has been shown in studies to actually decrease the amount of disability seen in patients, even five years after they stopped taking it (click here). This is a result previously unseen with any other MS drug, and may be due to the fact that Lemtrada is such a strong immunosuppressant that it forces the body to rebuild its immune system. This is a similar mechanism to some autologous stem cell treatments, in which a patient’s immune system is completely wiped out with very potent chemotherapy drugs, and then “rebooted” through the use of an infusion of bone marrow stem cells. The effectiveness of the drug does come at a price, though, as 30% of those taking it develop autoimmune thyroid disease, and a smaller percentage develop a serious blood disorder. Unlike Tysabri, though, for some reason the risk of serious infection seems to be quite low, despite the powerful immunosuppressive characteristics of Lemtrada. For patients willing to take the risk, Lemtrada, if and when it is eventually approved, may be the most effective MS drug available. Of course, it only works for RRMS patients; those with SPMS or PPMS are, as usual, left to flap in the breeze…

Having said all that, it sure would be nice if researchers would concentrate their efforts on finding ways to combat MS that don’t tinker with the immensely complex human immune system, since this approach clearly leaves patients open to potentially lethal side effects while doing nothing to actually cure the disease. Perhaps trying to figure out why the immune system goes bonkers in MS patients would be a good place to start…

♦ Just to bolster your confidence that science is aggressively attacking some of the most important issues facing mankind, a cure for baldness appears to be closer than ever (click here). Apparently, Vitamin D holds the key, and researchers around the world are scrambling to finally solve the horrendously tragic and heartbreaking epidemic of typical male pattern baldness, which has brought frustration and shame to men longing to be hairy since time immemorial. Just think about how much time and money is being spent chasing this cherished dream, and how many brilliant minds are dedicated to it. Forget about cancer, heart disease, ALS, and even MS – rejoice, for soon baldness may be cured! I know that I, for one, even with my head full of thick, voluminous hair, will celebrate mightily when the cure for baldness is finally announced. I’ll sit in my wheelchair and feebly raise a pathetically weakened fist as high in the air as my ever more afflicted muscles will allow, reveling in the knowledge that some perfectly healthy bald men will soon be able to proudly make appointments at barbershops and hair salons the world over. It’s all about priorities, people, and mine are definitely in order.

♦ This little bit of news is funny and sad at the same time. Seems an MS suffering grandfather in Scotland forgot he was married and wed his girlfriend, getting into all kinds of trouble due to the fact that he is now a bigamist (click here). The 50-year-old claims he thought his first wife had signed divorce papers, but he apparently forgot that she hadn’t.

In all fairness to the gent, he’d been separated from his first wife for several years, and MS does cause cognitive and memory issues in many who suffer from it. Furthermore, his second wife left him a few months after they were married, and the stress ensuing from this whole mess triggered a relapse, leaving him using two crutches. I’ve had women leave me emotionally crippled before, but this guy really got the short end of the stick. Or, in his case, sticks. In related news, a new study found that ginkgo biloba, an herbal remedy purported to improve cognitive function, had no effect on the cognitive abilities of MS patients (click here).

♦ If you’re in need of a little inspiration, this (click here) infographic about the Paralympics can provide plenty of it. Recently completed in London, this international sporting event for disabled athletes embodies the best of the human spirit. Though the bodies of participating athletes may not fit the standard definition of perfect, their hearts certainly defy definition.

I’ll leave you with the following video, in which a noted brain researcher recounts her experiences during and after suffering a stroke. These experiences provided her with startling and fascinating insights into not only the workings of the human brain, but of the universe and our place in it as well. I have an endless fascination for the mysterious place where science gently kisses spirituality, and this talk navigates that enigmatic realm as well as any I’ve ever heard. It’s 20 minutes long, but I guarantee it’s time well spent, and will provide you fodder for much contemplation…

Related articles

• Acorda's Ampyra fails main goal of post-marketing study
• Is Ampyra Any Good?

NIH Thinks I DON'T Have MS. Wow!

Well, after four months and a huge amount of poking and prodding, the National Institutes of Health Neuroimmunology team has decided that it's very unlikely that I have Multiple Sclerosis.

Holy shit.

Despite the fact that I've been disputing my diagnosis almost since the day I received it, and this news should be hugely validating, it's left me a little breathless, my head spinning faster than a chunky yuppie trying to lose her love handles at the local Bally's. Not exactly doing a victory dance here, and not only because I could just as soon dance as crap the Hope diamond.

Since July, I've made four visits down to Bethesda to be seen by the doctors at the NIH. During that time, I've undergone extensive testing, the results of which seem to confirm my long-held suspicions about my diagnosis. I only have one central nervous system (CNS) lesion of consequence, located at the base of my brainstem, and this lesion has not changed one bit during the eight years I've been getting regular MRIs. The lesion appears to be an old scar, and doesn't look to be "active". The very name "Multiple Sclerosis" implies more than one lesion, so right there we have a problem. Additionally, multiple tests reveal no evidence of inflammation or immune activity in my CNS, another hallmark of MS.

My test results look more like those of a patient who had suffered a damaging central nervous system "event" at some time in the past, had suffered disability at that time, and has remained stable since. In actuality, though, I've experienced a slow and steady progression of symptoms. When I first took note of the fact I was limping, 6 1/2 years ago, I could easily walk several miles, and the limp was the result of some slight weakness in my right knee, which only showed itself after a good long hike. Fast forward to today, when my right arm and leg are basically paralyzed, and I have increasing weakness and numbness on my left side as well. My progression has been continuous during this time, which is a complete disconnect from what my test results would appear to reveal.

My clinical presentation (disease history, physical neurologic exam) does resemble that of someone with PPMS, so it still could be that I have a very, very atypical form of that disease. The NIH thinks it more likely, though, that I'm suffering from some other progressive neurologic illness, of which there are more than a dozen. Unfortunately, none of them (including PPMS) currently has any treatment, and my symptoms and test results don't neatly fit into a diagnosis of any of them. I could be suffering from some new "Wheelchair Kamikaze Disease", and even though new diseases are usually named after the doctor that discovers them, if this is a new disease, I absolutely insist that it be called "Wheelchair Kamikaze Disease". Not exactly the rock star fame I was looking for in my younger days, but any port in a storm...

The other big news out of my examinations down in Bethesda is that I do have a vascular abnormality like those that are described in the CCSVI theory of MS. For those unfamiliar with this theory, which hypothesizes that MS is actually a vascular disease, I've described it in two previous posts on this blog, here and here. I believe this is must reading for anybody who has MS, as this theory could change everything we think about Multiple Sclerosis.

I had a CT venogram done several months ago, which revealed that I have a stenosis (narrowing) of my left internal jugular vein, very high up in my skull. This narrowing is directly adjacent to the central nervous system lesion on at the base of my brainstem that is causing all of my problems. Though they're far from sure, the NIH believes that this vascular abnormality could be related to my neurologic degeneration, so we're going to investigate that possibility further, through additional testing, to see if a connection can be made between blood flow problems and the damage being done to my nervous system.

There is currently a doctor in California who has done endovascular surgery on several dozen MS patients who have been shown to have stenosis, placing stents in their narrowed veins. So far the results have been encouraging, but I'm going to wait to see what the NIH and my primary treating neurologist (Dr. Big Brain) have to say on the matter. Despite the NIH results, Dr. Big Brain is not convinced that I don't have MS, and hasn't bought into the vascular theory, either. I have an appointment to see him on December 5, when we'll try to hash these things out.

On the cataract front, I'm less than thrilled with the results of the surgery, so far. I paid quite a significant sum out-of-pocket for special lenses to be implanted into my eyes, to replace my natural lenses which had developed cataracts. I was told these implants would very likely give me near normal distance vision, but that I would still require reading glasses. To a person who's been wearing glasses to correct his nearsightedness since age 6, the promise of "near normal" distance vision sounded almost too good to be true.

Well, it was. As it stands now, these miracle lenses have overcorrected my eyes, and now the wonders of modern medicine have magically transformed my former nearsightedness into farsightedness. Abracadabra.

After the second surgery, the doctor told me to buy some drugstore reading glasses so that I could read while my eyes healed. Surprise, surprise, when I put the reading glasses on, instead of clearing up my close up vision, they improved my distance vision. In order to read, or see a computer screen, I had to buy a second pair of drugstore reading glasses, which I wear in front of the first pair in order to see the fracking screen. So, yes, as I sit here writing this, I'm wearing two pair of drugstore reading glasses. Can a guy catch a break? To top it off, the glasses that correct farsightedness are the kind that make your eyes look really big, so now I can look forward to zipping around in my wheelchair all bug eyed. Incredible that despite being half paralyzed, I'm still as vain as a homecoming queen, isn't it?

I have my next follow-up with the eye doctor on November 30, when my eyes will be healed enough to get a final prescription for glasses, but if my eyesight has not improved by then, he's going to get quite an earful. Jackass.

Okay, deep breath, time to kick into high gear some of that Zen stuff I'm always talking about. But first I think I'm just going to curse a lot, like a Tourette's patient on Red Bull. Cover your ears...

More MS on the Internet

Image via Wikipedia

Since my last entry updated a post I made several months ago, I figured I'd keep the trend going by updating yet another post I made several months back, which was titled "MS on the Internet". That post was made up of a list of Multiple Sclerosis related websites that I find useful, and it received a good response from WK readers.

Since then, I've come across several additional websites that I think are of value. Most of these sites aren't devoted strictly to Multiple Sclerosis, but offer a wealth of information on neurology and general healthcare, in addition to having sections specific to MS...

Can you tell I spend way too much time on the web?

TheBrainMatters.org-This website is run by the American Academy of Neurology, and covers a wide range of neurologic disorders, including a section devoted to Multiple Sclerosis. It also has a "Find a Neurologist" tool, which users might find very helpful.

The Neurology Patient Pages-This site contains summaries of research studies from the journal Neurology, prepared especially for patients. Although not all of the studies are pertinent to Multiple Sclerosis, the summaries are a rich resource for information on all neurologic disorders.

Wellsphere-A general wellness information site, with lots of good material on nutrition and alternative and complementary therapies. The site hosts some educational and user-friendly patient communities, and has even named Wheelchair Kamikaze as one of their "Top Health Bloggers".

Patients Like Me-This is a unique website, which allows patients to set up their own profiles, and track the progression of their disease and the treatments that they undergo. Covering a wide range of conditions and diseases, this site allows users to "compare notes" with other patients who share similar experiences. The site also hosts some active patient forums.

The National Institute of Neurologic Disorders and Stroke-This is the official website of the NINDS, which is the arm of the National Institutes of Health responsible for all government-funded neurologic research. The site is a treasure trove of information on all neurological disorders, as well as info on clinical trials and patient resources.

ClinicalTrials.gov-A comprehensive registry of all federally and privately financed clinical trials conducted in the United States and worldwide. The listings include inclusion criteria as well as contact information for all of the trials. If you're interested in getting involved in a clinical trial, this is the place to look. The registry is easily searchable by disease and location.

MedlinePlus-A terrific site that includes information on the latest medical news, drugs and supplements, a medical dictionary, a medical encyclopedia, and a directory of physicians and hospitals.

NeurologyChannel.com-Run by physicians, the site offers a wide range of information and services, including a patient forum, and a section devoted to patient stories.

The Health Care Blog-An great site for commentary on healthcare issues and policy. Makes for some very interesting reading.

The Problem with Progression

Of late, the MS has been giving me a pretty good ass whuppin'. It's getting harder for me to stumble around my apartment, and I'm pretty close to making the decision to start using my wheelchair for indoor as well as outdoor mobility. Up until now, I've used the chair exclusively for my travels through the beehive of streets in New York, but now the uncomfortable realization is hitting that I also need it for excursions from the bedroom to the kitchen. It looks as if the progression of my disease is about to force me to crash through yet another psychological barrier.

During my first visit to an MS specialist, I remember the doctor going on about "stopping the progression of the disease". I was new to the world of MS, my head was spinning with thoughts of "spinal lesions", "lumbar punctures", and "brain MRIs", and I simply could not process what he was talking about. Progression? What the hell is progression? I have a little limp in my right leg, upsetting yes, but hardly the end of the world...

Well, now I'm all too well aware of the meaning of progression. In six years, that little limp has reached out and put a choke hold on much of the rest of my body, and try as I might, I just can't seem to wriggle free. I could list a litany of my defective body parts, but what's the point? It would most likely just need to be updated again next week. Each new day seems to bring with it a changing set of circumstances, and unfortunately, those changes don't ever seem to be for the better.

To state the obvious, the problem with progressive neurologic disease is that it progresses. Little by little, you lose yourself to your illness. As great a toll as this progression takes on the physical body, the psychological impact of watching yourself whither away over weeks and months and years cannot be overstated. Back in the dark ages of my MS experience, I'd sit in the neurologist’s waiting room and see other patients in their wheelchairs and scooters, and thank the heavens that I was not one of them. Of course, I knew that they did not just one day materialize disabled, and that they had arrived at their current physical conditions incrementally, over time. I just couldn't fathom that I would follow the same road. I'd look at those poor souls, my mind would reel, deliberately set me apart from them, and quickly force my attentions elsewhere.

Now, I'm the guy sitting in that waiting room in a wheelchair, and I can see the less disabled patients looking at me through familiar eyes. I make it a point not to appear dour or downtrodden, and I'm always quick with a wisecrack or two, but I know too well the quiet horror they are feeling. Truth be told, they are not wrong in feeling it. As good a spin as you can put on it, as upbeat and determined as you might be in the face of it, the prospect of doing battle with an insidious enemy that slowly swallows you from the inside out is a perfect example of why human beings come equipped with a healthy capacity for denial.

No matter what stage of the disease you're in, peering forward carries with it an element of dread. The endless road of progression, if left unchecked, must ultimately lead to an extremely ugly place. Along the way there are milestones to be reached; the first time you can no longer climb a flight of stairs, the first cane, the realization that you can no longer sign your name.

At first I measured the disease’s progressive toll in the slowly shrinking distances I could walk, first in miles, then blocks, then yards, and now feet. Every holiday and special event has become a psychological landmark, a yearly milestone from which I can look back to the same moment in previous years and assess just how much I've lost, while simultaneously wondering about the scope of the wreckage I'll be dealing with in another year’s time. Will this Super Bowl be the last that I can watch from a couch that I've walked to under my own power? Or the last that I will be able to feed myself chips and dip? Or the last that I'll be able to manipulate the remote control? Or, simply, the last?

Ongoing disease progression leaves us little time to mourn the losses we've suffered. If one were to literally lose a leg, as horrible as that would be, the trauma could be experienced, mourned, and then adapted to, leaving a person in a state of permanence, albeit an unfortunate one. With progressive illness, the losses just keep mounting, and life becomes a constant exercise in adaptation. I haven't had the chance to fully mourn the loss of the use of my right hand, because I'm aware that my left appears to be following suit. I watch people happily strolling through the park, and feel a deep yearning, but that yearning is shadowed by the apprehension of insults yet to come. As layer upon layer of disability piles up, the process of mourning any single loss gets overwhelmed by the sheer volume of them all.

Strangely, and thankfully, I've found that the reality of each new stage of disability does not approach the horror that accompanied the anticipation of it. Back in the days before my illness, I'd have never thought I'd have the capacity to adapt to the level of disability I'm now experiencing. I once would have categorized the possibility of my being forced to rely on a wheelchair as unthinkable, but when that moment arrived, the world somehow kept spinning. The loss of functionality in my right arm and hand has led me to learn how to do things with my left, and through all manner of adaptations, I've managed to maintain an acceptable quality of life. So far, at least, the realities of encroaching disability have not been as ghastly as I'd imagined they would be. I am constantly aware, though, that there will come a tipping point, when even the barest illusion of normalcy will disintegrate under the weight of some new undeniable reality.

Of course, I am not without hope. Even without intervention, MS is an unpredictable beast, and patients with the most aggressive forms can sometimes find themselves reaching plateaus for years at a time. Medical research is shedding new light on the disease on an almost daily basis, and the promise of stem cells to repair damaged nerve tissue is steadily moving closer to becoming a reality. Trials of neuroprotective agents are currently underway, and radical new theories about the very nature of multiple sclerosis are finally being given proper scientific scrutiny.

Still, though, the disease marches on, the struggles become harder, and, with the help of friends and loved ones, the best we can do is strive to stay rooted in the moment...