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Saturday, January 21, 2017

Clearing Up Misconceptions about MS


                                                                  
  

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Wednesday, January 18, 2017

Ocrelizumab Exclusive: Interview with Pioneering Researcher Dr. Peter Chin


                                                                  
  

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Written by: 

Wheelchair Kamikaze



Posted: 18 Jan 2017 01:15 AM PST
Dr. Peter Chin

Late last month I was contacted via email by a representative for the pharmaceutical company Genentech, asking if I would like to interview one of the researchers who played an instrumental role in the development of the new MS disease modifying drug ocrelizumab. At first I assumed I must’ve received the email as the result of some sort of clerical error, what with my being a mere blogger and all, but I figured if they’re offering, I’m accepting.

Thus, I present the below interview with Dr. Peter Chin, the Group Medical Director of Neuroscience at Genentech. Dr. Chin has been involved with the development of ocrelizumab for well over a decade, and was a pioneer in the study of the role of immune system B cells in multiple sclerosis. This line of thinking has upended much of what had previously been thought about the disease, as the working theory up until very recently was that immune system T cells were the primary culprits that should be targeted when developing drugs aimed at alleviating multiple sclerosis. Ocrelizumab is a very close cousin of rituximab, also known by its brand-name Rituxan, another Genentech product which many neuros have been using off label to treat their MS patients.

Ocrelizumab, an intravenous medication requiring infusions approximately every 6 months, has garnered a tremendous amount of attention of late, as it is the first drug ever to show efficacy in treating progressive MS in a late stage clinical trial and is in the process of being considered for approval for the treatment of PPMS (as well as relapsing multiple sclerosis) by the FDA. The drug has generated blaring headlines and hyperbolic chatter in the medical and mainstream press, and talking directly to Dr. Chin presented a valuable chance to cut through the clutter and get the pertinent info straight from the horse’s mouth. Not to insinuate that Dr. Chin is a horse; au contraire, he proved to be an extremely erudite gentleman during our extensive talk. He was also quite generous with his time, as our scheduled 30 minute interview lasted for nearly an hour.

The following interview is filled with a tremendous amount of important information. It’s been lightly edited for readability. I’ll publish it here without commentary and follow-up next week with my take on the potential promises and pitfalls of ocrelizumab, an intriguing new MS medication.

As you read through the interview, you’ll notice a brand-new feature on these pages called “WK notes”. These are explanations in everyday language of some of the more esoteric medical terminology that cropped up during the interview. And, if anybody’s wondering, “WK” stands for Wheelchair Kamikaze, not Wicked Kool.



WK: Dr. Chin, let me thank you for taking the time to do this interview. To start, could you explain the importance of the relatively recent research into the role of B cells in the Multiple Sclerosis disease process? I understand that when this research first started, it was not in the mainstream of general Multiple Sclerosis research.

Dr. Peter Chin: Genentech started collaborating with leading academic researchers at major universities to look into the possibility that B cells might be important in MS about 15 years ago. To some degree this was not the mainstream line of thinking, but there were researchers who had a scientific hypothesis and believed that B cells might be important because they are the cells that differentiate into cells that secrete antibodies, and antibodies are implicated in the disease pathogenesis (WK note: pathogenesis refers to the conditions that lead to the development of a disease). They are found in lesions and in the cerebral spinal fluid as oligoclonal bands (WK note: more commonly referred to as O-bands, these are one of the primary diagnostic indicators that neurologists look for when examining the spinal fluid of potential MS patients). So there was some rationale, and I think it was an exciting time when the first proof of concept studies unblinded, showing that B cells may play a more important role than anybody thought.

WK: Just to be clear, before this time it was assumed that this was a T cell mediated disease, is that right?

Dr. Chin: That’s correct. The vast majority of efforts in developing new medications up until that point were directed towards T cells.

WK: Genentech was the first to study the use of B cell therapies in MS with the drug Rituxan, whose generic name is rituximab, which was the precursor to ocrelizumab, correct?

Dr. Chin: Yes, that’s right. Genentech developed rituximab a long time ago for oncology, and we learned a lot about the medication from there. Rituximab provided a proof of concept that B cells might be important in MS, but we advanced another molecule that we believe has the best potential for long-term treatment from both the safety and efficacy standpoints for people living with MS, and that’s ocrelizumab. Ocrelizumab is a humanized molecule which is different from rituximab because rituximab is what we call a chimeric antibody, which has a portion of its protein sequence that is derived from mice. (WK note: a chimera is a mythical beast made up of the parts of different animals, such as a winged lion. Chimeric drugs are those that include the DNA of both humans and animals.) Ocrelizumab is a humanized molecule, meaning most of its protein sequence is human. That becomes important, particularly in a chronic disease, because ocrelizumab is hypothetically less likely to generate an immune response against the drug itself than a drug that includes more non-human DNA.

WK: Can you tell us a bit about the proof of concept studies that used rituximab to treat RRMS?

Dr. Chin: Yes, it’s important to recognize that these were small proof of concept studies, with a single dose of rituximab against placebo. It did show a reduction in MRI enhancing lesions, which was the primary endpoint, and also showed about a 50% reduction in relapses against placebo, in a six-month period. So it did provide some preliminary information that targeting CD20 positive B cells might be effective (WK note: CD20 is a protein that appears on the surface of a variety of different types of B cells). Around the same time, ocrelizumab was being studied in rheumatoid arthritis in a dose ranging study. One thing we looked at was multiple doses of ocrelizumab and their effects on B cells as well as efficacy and safety. We also looked at immunogenicity (WK note: immunogenicity is the ability of a substance to provoke a response in the immune system) and found that this was a molecule that had potential for chronic autoimmune conditions, and decided to advance ocrelizumab for Phase II development in RRMS, which led to the Phase III development program which was just published in the New England Journal of Medicine.

WK: PPMS trials were also done with rituximab about 10 years ago, too. Since I am suspected of having PPMS, I was tremendously interested in that particular trial. Can you talk a little bit about that trial?

Dr. Chin: The rituximab PPMS trial is a trial that I was involved in, actually, and it was a Phase II/III study of 439 patients comparing rituximab versus placebo. It was a single study, and it was a negative study. Meaning that the primary endpoint, which was the time to 12 week confirmed disability progression, was not significantly different than placebo.

WK: My understanding is that even though the trial as a whole was negative, when the data was looked at retrospectively there was a subset of patients – primarily those who were younger, less disabled, and had enhancing lesions – that did appear to gain benefit from the drug. Is that correct?

Dr. Chin: That’s right, although this finding was hypothesis generating rather than confirmatory, meaning it was not proven in the study.

WK: Okay, let’s talk about the ocrelizumab MS trials, which are creating chatter all around the MS community. Starting with the RRMS studies, some of the results reported were pretty astounding. Could you describe those results?

Dr. Chin: The phase III RMS studies were called OPERA 1 and OPERA 2 (WK note: RMS refers to both RRMS and Relapsing SPMS). These were two, two-year trials – double-blind, double dummy studies – comparing ocrelizumab head-to-head to the interferon beta 1a drug Rebif. Here the relapse reductions were 46% and 47% compared to interferon. There was also a 40% reduction in confirmed disability progression, and approximately 95% reduction in gadolinium enhancing lesions compared to interferon. These are very promising results from an efficacy standpoint, and have the potential to really change the way that MS is treated.

WK: Yes, those are extremely impressive results. Were there any instances of PML, the potentially fatal brain infection that has been seen in patients taking some of the other MS disease modifying drugs, in any of the patients in the Ocrelizumab trials?

Dr. Chin: No cases of PML have been observed in any of the ocrelizumab development trials.

WK: Okay, let’s move onto the PPMS trial, which is really generating tons of buzz. Could you please summarize the studies and their findings?

Dr. Chin: The ORATORIO study is the Phase III double blinded study, lasting more than 2 and half years, comparing ocrelizumab to a true placebo. The primary result of this study indicated a 24% reduction in the risk of 12 week disability progression. Importantly, there was also a 25% reduction in the risk of 24 week disability progression, which is generally considered a more robust outcome measure for disability progression.

That 25% reduction is the reduction in risk over the entire timeframe for all the patients that were included in the trial, and that’s at least 120 weeks, but there were patients who entered the study early in the treatment period that were on the drug for a longer period of time. So the 25% reduction in the risk of disability progression is the figure for the entire cohort for the entire length of the trial.

WK: Okay, so the data from the trial tells us that this new drug for people with primary progressive MS is not reversing disability or stopping the progression of disability, but it is slowing the accrual of disability. Is that a fair assessment?

Dr. Chin: Yes, the primary result of the study is the 24% reduction in 12 week confirmed disability progression. So that is not a measure of improvement, and you’re correct, it shows a delay in the progression of disability as measured by EDSS (WK note: EDSS is a scale that measures the level of disability in MS patients).

WK: Realistically, then, PPMS patients on ocrelizumab can expect that they probably will keep progressing, but it would be at a slower rate than if they were left untreated?

Dr. Chin: That’s a hard question to answer for any individual, but the overall results for the population of the study show a slowing of disability production as measured by EDSS, there is a slowing of the worsening of the timed 25 foot walk, which is another major end point in progressive MS trials. This is literally a measure of how long it takes to walk 25 foot feet. There is a slowing in the rate of brain volume loss, and, at least over the course of the trial, there appears to be a stabilization of the accumulation of T2 lesion accumulation. On this end point the placebo treated patients continue to accumulate T2 lesion volume and patients on ocrelizumab experienced a small decrease that was stable over the course of the two and half years or more.

WK: You previously noted that ocrelizumab was tested in trials for the treatment of rheumatoid arthritis. Weren’t those trials halted because of opportunistic infections and patient deaths?

Dr. Chin: There were opportunistic and serious infections observed in the Phase III program in rheumatoid arthritis. What’s important here is that rheumatoid arthritis is a different treatment paradigm. These are patients that are also on concurrent immunosuppressants in addition to ocrelizumab. (WK note: many of the rheumatoid arthritis patients in the ocrelizumab trial were taking other immune suppressing drugs in addition to ocrelizumab.)

WK: And ocrelizumab was also being trialed for treating lupus, and those trials also had to be halted for similar reasons, correct?

Dr. Chin: There were 2 studies in lupus. Ocrelizumab was studied in systemic lupus erythematosus (SLE), and that was discontinued primarily because the expectation for efficacy was low based on another study involving B cell targeting. The other study was on lupus nephritis, and there were serious infections that were observed, but the decision to halt was based on an assessment of potential benefits versus risks.

The same is true for the Rheumatoid Arthritis program. The potential for benefit/risk improvements over existing therapies, based on the data that were already on hand, was deemed not to be promising. So the studies were discontinued.

WK: Were any of these same problems – opportunistic infections and patient deaths – seen in either the RRMS or PPMS ocrelizumab trials?

Dr. Chin: The ocrelizumab Phase III safety results for MS overall were very favorable. This is the data that was just published in the New England Journal of Medicine. The proportion of patients in the relapsing study with any adverse event were similar to those who were on beta interferon, and the proportion of patients with any serious adverse event, including serious infections, were also similar to interferons. The same is true with the primary progressive MS trial, which was a slightly longer trial. When compared to placebo the proportion of any adverse event, any serious adverse event, or any serious infection was comparable to placebo.

WK: In looking over the ORATORIO PPMS trial results, it appears that there were higher rates of cancer among the ocrelizumab treated population when compared to the placebo population. I believe the numbers were 2.3% of the ocrelizumab population developed cancers, while .8% of the placebo group developed cancers. Is that of any real concern?

Dr. Chin: There is a numerical imbalance in the number of cases observed, but the overall numbers are small. This is not a confirmed risk, but I will say that patient safety is important to us and we do continue to monitor this in ongoing clinical trials. We don’t believe that the totality of the data supports a causal relationship, but we will continue to monitor this in our ongoing Phase III open label extension studies. So far, in the additional data we’ve accumulated, there is no increase in the rate of cancers being seen.

WK: The earlier rituximab trials demonstrated that there was a subset of the PPMS population on which the drug appeared to be effective – primarily younger patients who were less disabled and had enhancing lesions. In the ocrelizumab PPMS study this group made up about 26% of the test subject population, whereas in the general PPMS population the number of patients displaying those characteristics is thought to be somewhere between 10%-15%. So it would appear that the ocrelizumab study was populated with a higher percentage of patients who might be high responders than are present in the real-life PPMS population. Can you comment on this possible disparity?

Dr. Chin: The first thing I would say is that the study results are designed to assess the efficacy in the entire study population. So this was not a study only of patients of a certain younger age or only of patients who had enhancing lesions or did not have enhancing lesions. I say that because when you look at subgroup results, it’s important to recognize that these studies are not designed to address the efficacy in the subgroups. Also, I would note, that in data that we presented earlier this year that there is a directional consistency, meaning that there is still a reduction in disease worsening in patients who both had enhancing lesions and did not have enhancing lesions at baseline. This was presented at the ACTRIMS meeting in February 2016.

WK: Are there differences between the mechanisms rituximab and ocrelizumab use to eradicate CD20 B cells? 

Dr. Chin: There are differences in how they bind to CD20 molecules on the B cells. And there are differences in what we call effector function, and that’s the portion of the antibody that interacts with other elements of the immune system to remove the cells. So, yes, there are differences in the functions of the two molecules.

WK: The mechanism of ocrelizumab in PPMS patients that do have enhancing lesions – which indicate active inflammation within the central nervous system – would presumably be much the same as you would see in the RRMS model, in that the drug clearly reduces inflammation by targeting B cells. Can you propose a mechanism of action for ocrelizumab that would be beneficial for the vast majority patients with PPMS who don’t have signs of enhancing lesions or any other signs of active inflammation in their central nervous systems?

Dr. Chin: That’s a very challenging question, and a good question. I think what you’ve hit on is an area that the entire research community in MS is thinking about. It’s not a question that anyone can answer definitively at this point, because the mechanism of progressive MS and the evolution of progressive MS over time isn’t completely understood. I think there’s a recognition in the research community that the biology has become very complex and how intervening in one way will impact the disease is hard to predict. Genentech is a member of the Industry Forum of the International Progressive MS Alliance, a coalition of organizations that has formed to address the kinds of questions that you’re asking, so we contribute what we can to the understanding of progressive MS. But that’s a really big question that you’re asking.

I think our understanding of B cells currently, which I will acknowledge is ongoing and evolving, is that B cells do interact with T cells, and by removing B cells from circulation we may be breaking that interaction. We also know that B cells differentiate into plasma cells and plasmablasts which create antibodies, which might also be involved. (WK note: plasma cells and plasmablasts are among the more mature types of B cells circulating in the human body.) B cells also create a number of cytokines that also impact and potentially stimulate other parts of the immune system. (WK note: cytokines are chemicals secreted by cells that trigger actions in other cells.) There may be multiple ways that selectively targeting b-cells might be leading to efficacy.

WK: Just a couple of weeks ago we learned that the December 28, 2016 date for and FDA decision on the approval of ocrelizumab had been delayed until March 28, 2017. Can you shed some light on the reasons behind that postponement?

Dr. Chin: We did have an announcement about this extension of the date, and yes it’s March 28, 2017, which is the expected action date by the FDA. The FDA needs more time to review additional data that was submitted during the review, regarding the commercial manufacturing process. What I want to stress is that this is not related to the review of safety or efficacy data. It’s about the manufacturing process and the data regarding that process. This extension of the action date by the FDA is a commonly used procedural tool and they use it to allow more time to evaluate additional information. It’s not uncommon for questions that come up during the review, and as a result of those questions additional data get submitted. It’s just the nature of the process.

WK: As a final question, as a scientist who has devoted a large part of your career to studying MS and progressive MS, what do the trial results from the PPMS ocrelizumab studies indicate to you about the disease, and what can we look forward to in the future for what had previously been an untreatable and rather terrible malady?

Dr. Chin: I think the first thing I’d say is that the data that we just published in the New England Journal are really landmark data for a number of reasons. One, they highlight and confirm that B cells are important in MS, which is still a relatively new concept. That’s a major area of science that Genentech has contributed to that the entire community is continuing to work on. From a clinical trial results standpoint, this is the first molecule that has shown efficacy in both relapsing MS and primary progressive MS. It’s the first molecule under consideration for approval by the FDA for both RRMS and PPMS. It’s an exciting time and an exciting potential new medicine to be working on.

Particularly in regards to primary progressive MS, I want to make the note that Genentech is the only company that has actually done two Phase III studies on primary progressive MS. It’s something that we’ve been very committed to because of the unmet medical needs and the fact that there are no approved therapies. My great hope is that people will start to see that maybe we can do something about primary progressive MS, and build upon this first step with ocrelizumab, which is a very meaningful one.

WK: On behalf of all Wheelchair Kamikaze readers, I’d like to offer a tremendous thank you for doing this interview. On a more personal level, I’d like to thank you for devoting your career to unraveling the mystery of this dreadful disease. It’s tremendously important for a lot of people who suffer from all forms of MS, but especially those who have been without any proven treatment options for so long, who are stuck living with the misery that is progressive MS.

Dr. Chin: Thank you for that, Marc. I think it’s important for you to know that there are hundreds of people at Genentech and Roche who have worked on these primary progressive trials and the RMS trials for many years. I think I can speak for all of them that they do it with a passion for making a difference, understanding the degree of unmet need that’s out there.


I hope readers have found real value in the above interview. I’d love to hear your thoughts in the comments section.

As I stated earlier, I’ll follow this up next week with an essay on my thoughts about all things ocrelizumab, touching on many of the points that I discussed with Dr. Chin. A big thanks goes out to Genentech and Dr. Peter Chin for allowing me the chance to conduct this rather expansive interview. 

Until next time…

Wheelchair Kamikaze






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Sunday, January 15, 2017

HomeFeatured Our Senses Can’t Learn Under Stress


                                                                  
  

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Summary: Stress may impede perceptual learning and performance, a new study reports.
Source: RUB.

Stress is part of our everyday lives – while some thrive on it, it makes others sick. But what does stress do to our senses?
When we train them, we can sharpen our senses thereby improve our perceptual performance. The stress hormone cortisol completely blocks this important ability. In the current issue of “Psychoneuroendocrinology” neuroscientists of the Ruhr University Bochum (RUB) report on this finding.

“Previous research has already shown that stress can prevent the retrieval of memories. But now we have discovered that it also has a major effect on our perception and perceptual learning,” explains Dr Hubert Dinse, one of the authors of the study.

Tactile sense in training
In their study, researchers investigated how the sense of touch of 30 study participants could be changed after a training phase. Half of them received a medium dose of the stress hormone cortisol, while the other half received a placebo drug.

To make training comparable across all participants, the researchers employed the well-established approach of passive finger stimulation. Previous studies and several therapy approaches have shown that this method leads to an improved tactile acuity.
Image shows a hand and the chemical structure of cortisol.
To make training comparable across all participants, the researchers employed the well-established approach of passive finger stimulation. Previous studies and several therapy approaches have shown that this method leads to an improved tactile acuity. 
NeuroscienceNews.com image is for illustrative purposes only.
Tactile performance was assessed using the so-called “two-point discrimination threshold”. This marker indicates how far apart two stimuli need to be, to be discriminated as two separate sensations – the closer they are, the better the sense of touch.

No learning effect after cortisol
The placebo group improved their tactile acuity, as expected, by about 15 percent. In contrast, the cortisol given to the other group blocked almost all the stimulation-induced improvement. Cognitive psychologist Prof Dr Oliver T. Wolf explains:” Our data show that a single dose of cortisol not only disrupts memory in the hippocampus, but it also has a substantial effect on the plasticity of sensory areas of the brain.”

Cortisol blocks synaptic connections
In previous studies on a cellular level, neuroscientists have demonstrated that cortisol suppresses the strengthening of synaptic connections, and therefore the plasticity of the brain – its ability to learn. The team led by Hubert Dinse therefore suggests, their results could also explain by cortisol-induced suppression of synaptic plasticity.


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Journaling for MS: Why You Should Do It and How to Get Started


                                                                  
  



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Get Journaling for MS Today!

Being diagnosed with multiple sclerosis (MS) is a jarring experience to say the least. Each of us is riddled with new experiences, physical symptoms and relationship changes. The duty of learning new versions of ourselves is bestowed upon us; we are left to deal with life and it’s a tendency to force us all into situations that stretch our understanding of the world and our place within it. Journaling for MS can help in sorting out these experiences.
When a person is first diagnosed with MS, everything is confusing. We have to see lots of doctors and go through countless procedures and tests. Our bodies are experiencing their own unique expressions of symptoms.
We realize how unpredictable and sneaky this disease is. And we begin to realize that our lives will never be laid out before us, as we once believed that they would be, again.

Keeping Grounded

Keeping a daily journal is a great way to keep ourselves grounded. There is so much thrust upon a person who is entering this community of ours, the challenges and changes can feel overwhelming and isolating.
A journal can be a safe space. A home base of sorts, where we can go, to remember who we are beyond this disease.
It is hard to be honest to even our closest allies about what we are experiencing. How do we form the words and share our deepest fears when they are so private and heavy?
A journal is always there, waiting to listen. Ready to keep everything locked and sealed from public view. A journal never gets tired. It never judges. It never speaks for you. A journal is always ready for more.
There are always empty pages ahead, begging to be filled. Page after page, day after day, a journal will keep your story sacred. It holds your value as a reminder that you cannot be silenced, erased or ignored.

Reflecting Upon Progress and Pitfalls

A journal can help us to reflect upon how far we have come on our journey. We can track our losses and our gains to see what therapies or treatments are most helpful.
Each one of us has a pattern or sweet spot we can find in our daily lives to help the days pass. For me, journaling has helped in seeing my triggers for fatigue.
Once I was able to look back and see the things that were most commonly causing fatigue, I could tweak my behavior and live with more energy.
Journaling can also aid in understanding our symptoms better. When I was first diagnosed, I had no idea how long my relapse was going to last.
I can still, very distinctly, remember all of the “I don’t knows” that came out of my neurologist’s mouth. I may never know for sure how my body is going to behave tomorrow, but after nine years with MS, I have a fairly good idea and that helps me sleep at night. Journaling has helped me to keep track of the symptoms that I have gained, the symptoms that have progressed and the symptoms that have healed.

Finding Your Groove

It is much easier to move through relapses and all of the days in between when we can understand the effectiveness of our medications. Journaling is a great way of keeping track of our changes and reactions to medications over time.
When we are in the thick of it, it is nice to have the ability to look back upon our last relapse to understand a basic timeline of our body’s reactions to steroids and physical therapy. A relapse can feel like an eternity, but a journal can show the incremental goal posts towards normalcy again.
Keeping track of disease-modifying drugs is better done with a journal as well. Many of us struggle with our meds in one way or another; remembering to take meds consistently, keeping track of injection sites and recognizing negative physical reactions to medications, are all important aspects when living a life with a chronic illness.
Making a habit of logging these details on a daily basis aids in protection from the negative consequences that can come from drug fatigue and complacency.

Keeping Healthy and Fit


CONTINUE READING


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Selection of first-line therapy in multiple sclerosis using risk-benefit decision analysis.


                                                                  
  

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Bargiela D, et al. Neurology. 2017.

Abstract

OBJECTIVE: To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis.
METHODS: We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs). We performed sensitivity analyses varying PML risk, mortality and morbidity, and relative risk of disease worsening across clinically relevant ranges.
RESULTS: Over the entire reported range of NTZ-associated PML risk, NTZ as first-line therapy is predicted to provide a greater net benefit (15.06 QALYs) than FGL (13.99 QALYs) or GA (12.71 QALYs) treatment over 30 years, after accounting for loss of QALYs due to PML or death (resulting from all causes). NTZ treatment is associated with delayed worsening to an Expanded Disability Status Scale score ≥6.0 vs FGL or GA (22.7, 17.0, and 12.4 years, respectively). Compared to untreated patients, NTZ-treated patients have a greater relative risk of death in the early years of treatment that varies according to PML risk profile.
CONCLUSIONS: NTZ as a first-line treatment is associated with the highest net benefit across full ranges of PML risk, mortality, and morbidity compared to FGL or GA. Integrated modeling of long-term treatment risks and benefits informs stratified clinical decision-making and can support patient counseling on selection of first-line treatment options.
© 2017 American Academy of Neurology.

PMID

 28087821 [PubMed - as supplied by publisher]
SOURCE


MS Views and News

Subjective and objective assessment of physical activity in multiple sclerosis and their relation to health-related quality of life


                                                                  
  

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Krüger T, et al. BMC Neurol. 2017.

Abstract

BACKGROUND: Physical activity (PA) is frequently restricted in people with multiple sclerosis (PwMS) and aiming to enhance PA is considered beneficial in this population. We here aimed to explore two standard methods (subjective plus objective) to assess PA reduction in PwMS and to describe the relation of PA to health-related quality of life (hrQoL).
METHODS: PA was objectively measured over a 7-day period in 26 PwMS (EDSS 1.5-6.0) and 30 matched healthy controls (HC) using SenseWear mini® armband (SWAmini) and reported as step count, mean total and activity related energy expenditure (EE) as well as time spent in PA of different intensities. Measures of EE were also derived from self-assessment with IPAQ (International Physical Activity Questionnaire) long version, which additionally yielded information on the context of PA and a classification into subjects' PA levels. To explore the convergence between both types of assessment, IPAQ categories (low, moderate, high) were related to selected PA parameters from objective assessment using ANOVA. Group differences and associated effect sizes for all PA parameters as well as their relation to clinical and hrQoL measures were determined.
RESULTS: Both, SWAmini and IPAQ assessment, captured differences in PA between PwMS and HC. IPAQ categories fit well with common cut-offs for step count (p = 0.002) and mean METs (p = 0.004) to determine PA levels with objective devices. Correlations between specifically matched pairs of IPAQ and SWAmini parameters ranged between r .288 and r .507. Concerning hrQoL, the lower limb mobility subscore was related to four PA measures, while a relation with patients' report of general contentment was only seen for one.
CONCLUSIONS: Both methods of assessment seem applicable in PwMS and able to describe reductions in daily PA at group level. Whether they can be used to track individual effects of interventions to enhance PA levels needs further exploration. The relation of PA measures with hrQoL seen with lower limb mobility suggests lower limb function not only as a major target for intervention to increase PA but also as a possible surrogate for PA changes.

PMID

 28086828 [PubMed - in process]

Source 






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Understanding Comprehensive Care -


                                                                  
  

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Information showing below was written by The National Multiple Sclerosis Society

Understand the importance of comprehensive MS care and meet the healthcare professionals who will partner with you to manage the disease and your health.


Comprehensive Care


 IN THIS National MS SOciety ARTICLE



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MS Views and News
Providing educational information, resources and services for those affected by MS
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Impactful, sustainable solutions for people affected by MS


                                                                  
  

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 The Edward M. Dowd Personal Advocate Program aims to increase independent living capabilities and quality of life for people affected by MS whose health and safety are compromised by limited knowledge, understanding, and/or ability to access programs and benefits. Individuals in need of this service are identified by:
  • Multiple, urgent issues and significant MS-related symptoms and/or disability
  • Significant changes in physical or mental health, or cognition
  • Inability of family or caregiver(s) to provide care or cope
  • Isolation (including being homebound), living alone, or other health or safety risks
  • Lack of home care, adequate housing, or other vital services
  • Inability to identify needs, e.g., scattered assistance requests or signs of being overwhelmed
  • Imminent potential of admission to a long-term care facility




MS Views and News
Providing educational information, resources and services for those affected by MS
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