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Disclaimer: 'MS Views and News' DOES NOT endorse any products or services found on this blog. It is up to you to seek advice from your healthcare provider. The intent of this blog is to provide information on various medical conditions, medications, treatments, and procedures for your personal knowledge and to keep you informed of current health-related issues. It is not intended to be complete or exhaustive, nor is it a substitute for the advice of your physician. Should you or your family members have any specific medical problem, seek medical care promptly.
This MS teleconference will
be presented on Wednesday, September 12 at 7:00pm. This is entirely free and
callers do not need to be a Stony Brook patient to participate. It is open to
anyone affected by MS: patients and family members. Dr. Krupp will also answer
questions from participants.
To register and receive a
call-in number, call (631) 444-7832.
If you would like to submit
any questions in advance please just reply to this email or give your
question(s) when registering. Please pass this on to anyone you think
might be interested.
Thank you so much!
Dominique Stanley, Development &
A power outage is an inconvenience for everyone, but for people with disabilities it can become a life-threatening situation. Should some type of emergency arise, would you be ready? Prepare today for an emergency tomorrow. Don't be left in the dark!
RECOGNIZE ALL POTENTIAL HAZARDS, such as loss of electricity, gas, water, or telephone service. Flooding, street and store closings, blizzards, earthquakes, and hurricanes are several possible scenarios. Having some idea in mind of what you might be planning for can make emergency planning easier.
KEEP A LIST OF ALL SUPPLIES AND EQUIPMENT RELATED TO YOUR DISABILITY, along with where you keep these things in your home. Write down all supplies you will need for a period of at least three days, in case of evacuation.
COMPLETE A MEDICAL INFORMATION LIST. Talk with your doctor or pharmacist. Ask questions. What should I do if I run out of medicine or am unable to obtain it right away? How do I store my medication and what is its shelf life? Keep at least a seven-day supply of essential medications, and if possible extra copies of prescriptions.
Your medical information list should include:
Names of medications, dosages, times administered.
Copies of health insurance cards
Medical condition for which you take the medication
Prescribing doctor's name and phone number
Any known drug allergies, as well as any communication or cognitive difficulties.
BUILD A SUPPORT NETWORK of people that are willing to assist you in case of an emergency. Your support network might include trusted neighbors, church members, friends, or relatives. These people will assist you with evacuation procedures, ascertain that you have all the supplies you need, and determine that your equipment is working properly.
EMERGENCY STAPLES include: *Bottled water (about 3 gallons per person) * Several flashlights in various locations
By: MSF Staff and reviewed by the MSF Medical Advisory Board
It is often said that good things take time. Clinical trials may be a prime example. In the U.S., for example, it usually takes just over fourteen years and $500 million dollars for an experimental drug to make the arduous journey from laboratory to patient.
Sponsored by a pharmaceutical company, a health-related government agency, or sometimes a university, the purpose of a clinical trial is to determine the safety of a particular medication as well as its efficacy against various diseases and medical conditions.
Before a new drug can be studied in terms of its potential effect on humans, it is first subject to pre-clinical test-tube analysis and/or animal studies to establish toxicity. This information is then assessed for risk and benefits to determine its acceptability for humans.
Next, the sponsor of the proposed drug will submit a plan to the FDA for testing on humans. This must include all pertinent information regarding animal testing, drug composition and manufacturing, qualifications of study investigators as well as a guarantee of protection for trial participants. This information is called the Investigational New Drug Application (IND). The treatment trials, which fall into three distinct phases, can now begin.
Phase I provides initial exposure of humans to a particular drug. This phase is concerned primarily with how the drug works in healthy participants. Is it safe? What are the side effects? What will the appropriate dosage be? The FDA will then evaluate all data before the drug progresses to the next phase.
Phase II incorporates a larger group of participants in order to better assess the efficacy of the drug. These participants are patients exhibiting a particular condition or disease. Rating scales are used to record data specifically geared toward the effects of the drug on the patient's disease or condition, as well as side effects.
Phase III compares proposed treatments with existing drugs. The FDA verifies all information obtained from the clinical trials thus far and also inspects the manufacturing facility to ensure that the highest possible standards of quality are being met. Much of the information provided on medication labels or inserts will be obtained during this phase.
Despite the risks involved, there are countless reasons why participation in these trials can prove beneficial. Participants receive free medical testing from specialists who have the most current information on their disease. There is the potential for a positive response to the medication, leading to improvement of a participant's condition. Also, manufacturers become more knowledgeable, their decisions more educated, creating safer, more effective medications.
BACKGROUND:Magnetic resonance imaging (MRI) is important in the early diagnosis of novel or relapsing multiple sclerosis (MS). In addition, the optimal MRI protocol plays an important role in detecting MS plaques.
PURPOSE:To find the best time to detect MS plaques on MRI after Gadobutrol injection.
MATERIAL AND METHODS:Sixty-two relapsing-remitting type MS patients, (56 women, 6 men) with the mean age of 31 ± 7 years were enrolled into this study. The patients underwent T1-weighted MRI scan without contrast agents. Subsequently, Gadobutrol was injected (0.1 mmol/kg) and MRI scanning was repeated after 30 s, 5, 10, 15, and 30 min of Gadobutrol injection. The size, signal intensity, and enhancement pattern were determined for each plaque by contrast-enhanced T1-weighted images.
RESULTS:Enhancing plaques were seen in 42 out of 62 patients. The mean number of enhancing plaques was 4 ± 8 plaques after 30 s of contrast injection. This figure increased to 7 ± 13 plaques after 15 min and 6 ± 10 plaques after 30 min. The signal intensity and size of plaques increased progressively, and the maximum signal intensity and plaque size were seen after 30 min (P < 0.001).
CONCLUSION: The maximum number of enhancing plaques in MS patients was detected 15 min after contrast agent administration and the size and signal intensity of the lesions also increased remarkably at this time.
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I want to discuss "The Approved Disease-Modifying Therapies for MS:
How Will Recent Data Impact Their Utility?" So
here's the CombiRx trial, which is a trial that was funded by NIH. I was
the principal investigator. So we have 1,008 patients. We randomized them
to either receive interferon beta-1a once weekly, or glatiramer acetate, or
everybody took eight injections, so it was a matching placebo, but there
was no full placebo-placebo arm. Everybody got something. And we wanted to
see if the combination would be superior. What we showed is that for
annualized relapse rate at 3 years, there was no real difference between
the combination and the better of the two agents. And so it turned out that
glatiramer acetate actually did the best alone, and both the combinations
of glatiramer acetate were significant better than interferon beta-1a over
3 years. The
other thing you should pay attention to here is how low these relapse rates
are. That's one exacerbation every 9 years, every 8 years. Even for
interferon beta-1a, that's one exacerbation every 6 to 7 years. These are
extremely low rates for our agents. For MRI,
in fact, the combination was significantly better at reducing
gadolinium-enhancing lesions, combined unique activity, and also for a new
metric called disease activity-free status. But that's all driven by the
MRI, and it's an interesting paradox that even when we went out into our
extension phase, we couldn't account clinically for that MRI difference.
And so we're looking to see what that means over time. back to top
This is a paper that came out of Vancouver in JAMA, trying to make comparisons of what
happens to people over time when they're put on interferon as opposed to
those that weren't. The
problem here is that you're comparing apples, oranges, pears, and
persimmons, because you're taking individuals who you choose to put on
therapy, individuals who either you or they choose not to go on therapy,
versus natural history controls. If you just take individuals in the 21st
century who are on placebo and compare them to people who are on active
agents—interferon beta or glatiramer acetate—in the 1990s, placebo was
better. They had lower relapse rates on placebo in the last 5 to 6 years
than they did on active drug in the '90s. Now,
they will tell you that they've made statistical adjustments for all of the
underlying differences between the populations. And you do this to try and
eliminate bias. In this study, they concluded that there was no effect on
disability progression over time. A similar study done in Italy several
years ago came to just the opposite conclusion. Again, if you want to see
if one treatment's better than another, even no treatment, you've got to do
it in a controlled study. back to top
Fingolimod has been approved now for a couple of years. It was the first
orally available agent, and this was based on initially two studies,
TRANSFORMS and FREEDOMS, and then a third study, FREEDOMS II. In the
developmental program, they showed in FREEDOMS here that fingolimod was
superior to placebo. There wasn't much difference between 0.5 and 1.25
[mg], so only the 0.5 [mg] was approved. The side effect profile of 0.5
[mg] was better than 1.25 [mg], and it worked on reducing annualized
relapse rate. It worked on MRI. And it worked on disability measures. The
other study they did was a 1-year study going head-to-head against
interferon beta-1a given once weekly, and in terms of reduction of
annualized relapse rate, it was superior. back to top
When you took the individuals who had been on the interferon beta-1a and
then switched them onto fingolimod, you got a reduction. These are
open-label extension studies. They show you that you're probably getting an
effect, but they're not as rigorous as when you have them under the
controlled clinical trial experience. back to top
Their third phase 3 trial was the FREEDOMS II. It confirmed the annualized
relapse rate reduction. Here was the 48%. And what didn't happen in this
trial was they didn't have a change in disability. It just works out that
been interesting in the FREEDOMS developmental program is that fingolimod's
the only therapy we have that, to my mind, makes sense when you look at
brain volume measurements. And I choose that word carefully. I'm looking at
brain volume, not brain atrophy, because atrophy presumes you actually know
what the pathologic cause is of the change in brain volume. And what was
nice about the fingolimod program is, at every measurement—6 months, 12
months, 24 [months], even out into extension—there was more loss of brain
tissue in the placebo group than in the treated group. And that mirrors the
clinical effect, and it makes sense. We don't have that with any other
agent that's out there at the present time that I've seen. back to top
Also, early onset of effect. So one of the things that we've argued about
over the years is how quickly these drugs work. And one could even make the
argument that we shouldn't pay much attention to the first 3 months of
on-study behavior, because we may be skewing our entire population response
by activity that's happening early on before the drug could take effect. In this
particular analysis of fingolimod they showed that there's an effect very
early on. So free from confirmed relapse at 3 months, 6 months. The numbers
stay the same, suggesting that the benefit's coming on fairly rapidly. back to top
Now, let's switch to teriflunomide. So teriflunomide has been around also
for a little bit now. It was our second oral agent. This was their first
pivotal trial, the TEMSO study. Again, randomizing individuals to two doses
plus placebo. And what
they found was that there was a 30-some percent reduction—modest
reduction—compared to placebo. The higher dose also reduced disability here
by about 30%. And so that was a good result. It ultimately led to approval.
back to top
TOWER was their second phase 3 placebo-controlled study. Similar results, a
little better reduction here in [the] 14 [mg], and in fact, while both
doses were approved, we prefer the 14 [mg]. And what's interesting here
with TOWER and TEMSO is both studies produced a reduction in disability. So even
though this is a relatively modest reduction in annualized relapse rate,
this is the only agent that's approved that reduced disability
significantly in their two studies. back to top
This is the disability numbers. And again, it's in the 14-mg dose.
Reasonably well tolerated. This is the side effect profile: hair thinning,
diarrhea, nausea, and neutropenia. Actually, pretty reasonably well
tolerated. The hair thinning is more upsetting to hear about than the
reality of it, but nevertheless it's there, and we have to tell folks about
it. back to top
So now we have three pills over the course of two and a half years. So this
is dimethyl fumarate. It just came out based on two studies. The
first was this DEFINE study comparing dimethyl fumarate twice daily and
three times daily, and fortunately twice daily was no different—actually,
even a little bit better—than three times daily. In this
study, there was a difference in disability in the twice-daily, so it
succeeded in the major outcomes, and it also had differences in effects on
MRI. In all
of the studies that we're showing you, both the ones that have led to
approved agents and the ones that Bob will show you that are in the
pipeline all have this consistency of effect—that they reduce annualized
relapse rate, they reduce gadolinium-enhancing lesion number, they reduce
volumes and such. And even if they don't have a significant effect on
disability, they all trend in the right direction. So there's a certain
consistency there that gives us confidence that our agents are working. back to top
Okay, their second phase 3 study was CONFIRM. Here, there is, again, the
two doses—240 mg twice daily, three times daily—versus placebo. And then
they had an active comparator—smaller numbers, but active comparator—of
glatiramer acetate not as a direct comparison, because it wasn't powered as
a head-to-head study, but as a tracking arm to just give you an idea of
where it sits. So here,
again, similar results to what they saw in their initial study. And this
study, three times daily did better than two times daily, but not
significantly better. And those numbers were higher than what we saw for
glatiramer acetate, but not necessarily significantly different. But they
did not make a significant change in EDSS progression. Similar therapeutic
effect on all of the MRI metrics. So based on these two studies, this drug
got approved last month. back to top
This was a study, RESTORE, looking at what happens when you stop
natalizumab. So natalizumab has a couple of issues associated with it. A
very good agent; we've had good results with it. But you know there's this
issue of PML. And there's also been this issue of potential rebound when
you stop the drug. And so
they did this study, taking people who had been on natalizumab, and then
stopping them for 24 weeks. It's an interesting design. And then seeing if
you can alter their behavior over those 25 weeks by either having them on
nothing, interferon beta-1a once weekly, glatiramer acetate, or pulses of
methylprednisolone. back to top
And the answer was that they all got activity back, and the activity
started to come back at 12 to 16 weeks, around the same time as you started
to see a loss of the biological effect of and binding to the receptor from
the agent, and it was both clinical and by MRI. And I
think probably the take-home message is, don't leave patients off of
natalizumab for 24 weeks, that there is this issue of potential rebound,
and what we're seeing is that we ought to get them onto something else much
sooner, if at all possible. back to top
So from the update on current agents, a combination of interferon beta-1a
and glatiramer acetate was no better than GA alone. Data
highlighting the clinical benefits of fingolimod in patients with MS
continue to accumulate. The clinical efficacy of teriflunomide is confirmed
in two randomized placebo-controlled trials. Dimethyl fumarate is
efficacious and was recently approved for the treatment of MS. Interruption
of natalizumab treatment results in a high rate of recurrence of MRI and
clinical disease activity. back to top
The Food and Drug Administration has issued an alert concerning the multiple sclerosis drug fingolimod, after a patient in Europe developed a rare and serious brain infection while taking the medication. Fingolimod is sold under the brand name Gilenya by Novartis (NYSE:NVS).
The agency says that this is the first reported case of the disease progressive multifocal leukoencephalopathy (PML) in a patient receiving Gilenya, who had not previously been on Tysabri (natalizumab), an intravenous MS drug previously associated with a higher risk of PML.
Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology, announces today that they have completed enrollment in the Translate MS-Repair Phase Ib multiple sclerosis (MS) trial.
The trial is a randomized, placebo controlled, Phase Ib study in multiple sclerosis (MS) patients treated with Trophos' olesoxime as an add-on therapy to Interferon beta. In three months, 44 patients have been recruited in three investigational sites in France. The first subject was enrolled on April 2 and the last subject on July 11, 2013.
Though many disease-modifying treatments effectively address the inflammatory episodes in relapsing remitting MS, they have almost no effect on the long term disability associated with MS resulting from progressive neurodegeneration. Promoting remyelination and providing neuroprotection are new concepts for the treatment of MS. Trophos' olesoxime is the most advanced oral small molecule to demonstrate these activities in relevant preclinical models.
The Phase Ib study will evaluate safety, tolerability and PK data of a six month treatment with olesoxime in MS patients stably treated with interferon beta. In addition, the study is also planned to analyze multi-center feasibility of potential imaging biomarkers as surrogate outcome measures.
The 24 month Translate MS-Repair project is funded by the French Agence Nationale de Recherche (ANR) through their Recherches Partenariales et Innovation Biomedicale 2012 program. The Translate MS-Repair consortium is led by Trophos and includes Assistance Publique Hopitaux de Marseille, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Reims, Centre National de la Recherche Scientifique, Institut national de recherche en informatique et en automatique.