Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag “drugs”

Swedish Study Compares Rituximab with Approved Therapies for Relapsing MS

  • Researchers from Sweden used medical records to evaluate treatment outcomes in people whose initial therapy for MS was rituximab (an off-label therapy that targets immune B cells) compared to those given an approved MS disease-modifying therapy.
  • A higher proportion of people initially given rituximab remained on it, compared to those remaining on their initial therapy in the other groups.
  • Understanding which individuals do best on what therapies is important for enabling people with MS to make the best treatment choices. For this reason, results of controlled trials – several of which are now underway – are needed to truly understand the comparative effectiveness of MS therapies.
  • The report was published online January 8, 2018 in JAMA Neurology.

DETAILS
Background: An important question in the treatment of MS is whether to start treatment for relapsing MS with a powerful therapy at the outset (called induction therapy), or to take a more traditional approach of starting with less powerful therapy and ramping up to a more powerful approach if relapses or other signs of disease activity continue (called escalation therapy).

Researchers from the Karolinska Institute (Stockholm, Sweden) set out to compare outcomes of people receiving induction therapy with a drug called rituximab, which is not specifically approved for the treatment of MS, compared to those receiving escalation therapy with one of the approved disease-modifying therapies. The investigators tracked whether the participants remained on therapy or discontinued it, which is an indirect measure of how well the treatment performed.

Rituximab: Rituximab is a monoclonal antibody (a protein made in the laboratory) that targets a specific protein (“CD20”) on the surface of immune B cells. B cells are known to be involved in the inflammation and damage to the brain and spinal cord in MS. Rituximab is FDA-approved for the treatment of several conditions including some cancers and rheumatoid arthritis, and it has been used “off-label” to treat several immune-mediated conditions, including MS. Rituximab is given by intravenous (into a vein) infusions every six months. A similar B-cell therapy approach that is manufactured differently, called ocrelizumab, was approved by the FDA in 2017 for the treatment of relapsing MS and primary progressive MS.

The Study: The researchers used data from the Swedish MS Registry and medical records of 494 people from two counties in Sweden who had been recently diagnosed with relapsing-remitting MS. About 24% had been started on rituximab; other initial therapies included injectable therapies (such as interferons and glatiramer acetate = 43.5%), oral therapies (dimethyl fumarate =17.4% and fingolimod =3.4%), and natalizumab given by IV infusion (24.3%). The key outcome measured was the proportion of people who discontinued specific therapies.

Results: A higher proportion of people given rituximab remained on it, compared to those who received other initial therapies. The reasons for therapy discontinuation differed by type of treatment, but the most common reasons were side effects, disease activity or pregnancy. The authors also reported a trend for increased relapses and brain lesions in participants using treatments other than rituximab.

This study was funded by the Swedish Medical Research Council and others. The report, by Drs. Fredrik Piehl, Mathias Grandqvist and others (Karolinska Institute), was published online January 8, 2018 in JAMA Neurology.

Comment: Understanding which individuals do best on what therapies is important for enabling people with MS to make the best treatment choices. Unlike well-designed clinical trials that have protocols for patient selection and assessment of outcomes, and that randomly assign participants to treatment groups, this observational study was not able to account for factors that determined why any particular therapy was prescribed for any individual, or for all factors that may have triggered an individual or doctor to discontinue a particular therapy. Results of controlled trials – several of which are now underway – are needed to understand the comparative effectiveness of MS therapies.

 

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Canadian Researchers Uncover Rare Gene that Increases Risk of Progressive MS

Researchers at the University of British Columbia have uncovered a rare gene mutation that appears to dramatically increase the risk, in some individuals, of developing a severe form of progressive multiple sclerosis. While the cause of MS is not known, scientists believe several different factors, including susceptibility genes, may interact to trigger the disease. The gene was discovered in two unrelated families that had multiple members with MS. The researchers also determined that the gene (NR1H3) contains instructions for a protein called LXRA, which is thought to be a control switch for genes involved in many functions, including some that help control inflammation and integrity of nerve-insulating myelin in the brain and spinal cord. This type of discovery can provide crucial clues to biological pathways that underlie MS, and may lead to new approaches for stopping MS and restoring function. The study, by Drs. Carles Vilariño-Güell, Weihong Song, A. Dessa Sadovnick and others, was funded in part by the MS Society of Canada and appeared in the journal Neuron on June 1, 2016.

German Study Suggests Leukemia and Colorectal Cancer Rates Increased with Mitoxantrone Use for MS

Summary

  • A study of 676 people with MS treated with the MS therapy mitoxantrone in Germany reveals that the rates of acute myeloid leukemia (a type of cancer) and colorectal cancer were significantly increased above what would be expected in the general population there. Rates of other cancers were not increased.
  • The authors note that if the findings are confirmed, recommending colonoscopy after treatment may be advisable, since if found early enough, colorectal cancer is curable.
  • The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Background: Mitoxantrone is a powerful immune-suppressing therapy. Prior to its approval for use in MS, it was used only to treat certain forms of cancer. It acts in MS by suppressing the activity of immune T cells, B cells, and macrophages that are thought to lead the attack on nerve-insulating myelin. The U.S. Food and Drug Administration approved mitoxantrone for reducing neurologic disability and/or the frequency of relapses in people with secondary progressive MS or worsening relapsing-remitting MS. The total lifetime dose is limited to avoid possible heart damage. Acute myeloid leukemia has been previously reported in people treated with mitoxantrone for MS or cancer.

The Study: Investigators identified 677 people with MS seen at the University of Würzburg MS center between January 1994 and December 2007 who had received mitoxantrone. They were able to follow up with 676 of these patients.

The results show that 37 people developed cancer after taking mitoxantrone, including nine cases of breast cancer, seven cases of colorectal cancer, and four cases of acute myeloid leukemia. The rate of acute myeloid leukemia was 10 times that seen in the general population in Germany. The rate of colorectal cancer was three times that seen in the general population in Germany. The rate of breast and other cancers was not increased over that seen in the general population in Germany. Older age at treatment was associated with increased risk of cancer, but not prior use of other immunosuppressive treatments, or duration of treatment with mitoxantrone.

The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Comment: The authors state that if the findings are confirmed, “posttreatment colonoscopy might improve the risk-benefit ratio of this highly active immunosuppressive drug,” since if found early enough, colorectal cancer is curable. They also note that mitoxantrone is currently the only MS therapy approved for treating secondary progressive MS, and that the overall rate of cancers may still justify the use of mitoxantrone in people who are severely affected with MS and where there are no better treatment options available.

Read more about mitoxantrone
Read more about treating secondary progressive MS
Read more about making treatment decisions in MS

 

Case of PML Reported in Person Taking Tecfidera®

In December 2014, important label changes were made to the prescribing information for Tecfidera® (dimethyl fumarate, Biogen Idec) including information regarding an individual who developed PML. Most recently, Biogen has confirmed report of a second case of PML (progressive multifocal leukoencephalopathy, a viral infection of the brain that often leads to death or severe disability) that occurred in a person taking Tecfidera. According to the company, the 64-year-old patient has primary progressive MS and experienced severe and prolonged lymphopenia (decreased white blood cells) during treatment with Tecfidera. Severe and prolonged lymphopenia is a known risk factor for PML and Consideration should be given to interrupting treatment if lymphocyte counts are low for more than six months. The patient is stable and is not hospitalized. Biogen has reported the case to the U.S. Food and Drug Administration (FDA).
PML is caused by the re-activation of a virus called the JC (John Cunningham) virus, a common virus to which many people have been exposed. PML has emerged in people using other medications, including the MS treatment Tysabri® (natalizumab, Biogen), and the MS treatment Gilenya® (fingolimod, Novartis AG).
It is not possible at this point to determine a person’s risk for developing PML because there have been so few cases in people taking Tecfidera. There have been two reported cases of PML in people with MS among the more than 155,000 individuals who have been treated with Tecfidera to date.
The symptoms of PML are diverse and can be similar to MS symptoms. For this reason, individuals should be alert to any new or worsening symptoms and report them promptly to their MS healthcare provider. Learn more about the risk factors and symptoms of PML from the web site of The PML Consortium. Individuals who have concerns about this report should discuss it with their MS healthcare providers.
If and when the FDA or Biogen provide additional information or recommendations for people taking Tecfidera or other MS medications, the National MS Society will share it as soon as possible.

Recent Update to Gilenya Prescribing Information

 A recent warning and precaution has been added to the prescribing information for Gilenya® (fingolimod, Novartis AG), an oral disease-modifying therapy for relapsing forms of multiple sclerosis. The warning adds Cryptococcal fungal infections to the list of possible infections for which people taking Gilenya are at increased risk. Anyone receiving this or other medications that can compromise immune system function should promptly report any new or worsening symptoms – both MS-like symptoms and other symptoms – to their neurologist.
The updated prescribing information approved by the U.S. Food and Drug Administration states that there have been cases of cryptococcal infections, including cryptococcal meningitis, reported in people taking Gilenya. Individuals and their healthcare providers should be alert to symptoms and signs that could indicate cryptococcal meningitis. This rare condition can be managed if it is diagnosed and treated promptly.
Cryptococcus is a type of fungus that is commonly found in the soil throughout the world. The fungus becomes airborne and people may breathe in microscopic amounts. Most people never get sick from breathing the fungus; cryptococcus typically infects people who have compromised immune system function – which can occur from illness, or due to the effect of some medications, including some medications that are prescribed to treat MS.
Infection with cryptococcus is uncommon, but it can be very serious and even lead to death if untreated. It is important to recognize the infection early and treat it promptly. The usual sites for cryptococcal infections are the lungs and the central nervous system (brain and spinal cord).

Symptoms of a lung infection may include:
• cough
• chest discomfort
• shortness of breath
• low grade fever
• weight loss
• a general sense of feeling unwell
Central nervous system infections may produce numerous symptoms including:
• headache
• confusion
• stiff neck
• light sensitivity
• mild fever
• nausea and vomiting
• vision change
• unsteady walking
• change in speech
• seizures
• abnormal muscle movements
The increased risk of many types of infection is also pertinent to people with MS who are receiving other powerful immune modifying or suppressing therapies. Therefore, it is important when receiving medications that can compromise immune system function to promptly report any new or worsening symptoms – both MS-like symptoms and other symptoms, such as those mentioned above – to your neurologist. It is also important to speak to with your doctor before making any changes to your medications.

Download the updated prescribing information (.pdf)

Download the updated medication guide for patients (.pdf)

Experimental drug that may repair nerve damage in MS moves forward

A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin according to a study that will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
“This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain, and advances the field of neuro-reparative therapies,” said study lead author Diego Cadavid, MD, with Biogen in Cambridge, Mass., and a fellow with the American Academy of Neurology.
The Phase 2 study involved 82 people who had their first incident of acute optic neuritis, a disease that typically affects one eye and is characterized by inflammation, damage to the nerve fibers and loss of myelin within the optic nerve. It is estimated that about half of people with optic neuritis will later develop multiple sclerosis.
All participants were treated with high dose steroids and then randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were then assessed every four weeks for six months and a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.
The main finding of the study focused on the latency of the visual evoked potential (VEP), a test that measures the visual system’s ability to conduct electrical signals between the retina and the brain. The results showed that people treated with the experimental drug and who did not miss more than one dose (per protocol population) had significantly improved conduction as measured by latency recovery compared to people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34 percent, compared to placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41 percent over placebo.
In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (within 10 percent of the normal eye) more than doubled, from 26 percent on placebo to 53 percent on the drug.
A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects.
“More studies are needed to evaluate whether these changes lead to clinical improvement,” said Cadavid.
A second study of anti-LINGO-1 in people with multiple sclerosis is ongoing.
See more at: http://www.neuroscientistnews.com/clinical-updates/experimental-drug-may-repair-nerve-damage-ms-moves-forward#sthash.KsNzebw1.dpuf

Give-away

The Giveaway for Mom’s Story on Amazon has ended. Thanks for participating. Mom’s Story, a Child Learns about MS is available on Amazon in paper: http://www.amazon.com/Moms-Story-Child-Learns-About/dp/147835819X/ref=tmm_pap_title_0?ie=UTF8&qid=1427210007&sr=1-1

and as an ebook on Kindle: http://www.amazon.com/Moms-Story-Mary-Nickum-ebook/dp/B00C0BO9TA/ref=tmm_kin_swatch_0?_encoding=UTF8&sr=1-1&qid=1427210007

Also Available:
http://www.barnesandnoble.com

Study: Genetic variant may be MS risk factor

In a new study, researchers testing DNA in siblings with MS discovered a genetic variant in women that may increase risk of developing multiple sclerosis. According to study authors, the variant may be the one of the strongest genetic risk factors for MS discovered to date.

Researchers at the University of Illinois at Chicago were able to test three sisters among a group of five siblings between the ages of 23 and 26, all diagnosed with MS. What they found was a genetic change known as a single nucleotide polymorphism, or SNP – a change in a single base-pair of the DNA – in a gene called STK11, which plays a role in tumor suppression and is believed to have several roles in brain function. They found the variant in all three they tested.

To determine if the SNP could be a contributing factor to the siblings’ multiple sclerosis, the researchers screened DNA samples from 1,400 people – 750 with MS and 650 without – provided by Jorge Oksenberg at the University of California, San Francisco, who is a leading expert on the genetics of MS. They found that the SNP was 1.7 times as prevalent in women with MS as in women without the disease, making it one of the highest known genetic risk factors for MS.

Based on their analysis, the researchers estimate that the STK11 SNP is present in about 7 percent of the general population. But because far fewer people develop MS, other genetic or nongenetic factors must play a role in the development of the disease, said senior author Doug Feinstein, professor of anesthesiology at UIC and research biologist at the Jesse Brown VA Medical Center.

The variant occurs almost twice as often among women with MS as in women without the disease, making it “one of the strongest genetic risk factors for MS discovered to date,” said Feinstein.

The findings were published in the journal ASN Neuro.

Writing Mom’s Story

I began writing the story in late 2007. Actually, I began the story in February 1978. Immediately after getting out of bed that February morning, I couldn’t stand. The room was whirling, my stomach was churning. I sat on the edge of t he bed until my head cleared a little and I could stand. I tried to dress, but wasn’t able to bend down without the room spinning again and the nausea returning. I made a doctor’s appointment. He couldn’t find anything and treated me with Dramamine for a mild middle ear inflammation. It cleared after about a week and I put the occurrence in the back of my mind. In August of the same year, I awoke one morning with a gray spot in the vision of my left eye. It enlarged over the morning. By afternoon, my vision in my left eye was limited to the extreme outer edges. Being Saturday, I went to the Emergency Room, convinced I was going blind. An Ophthalmologist happened to be on duty. He diagnosed the problem immediately as optic neuritis and prescribed prednisone. That cleared in about eight weeks.
Fast forward to 1989. I had been a “normal volunteer” at the National Institutes of Health for several years. I was asked if I would volunteer for an MRI. They said it’s easy if you’re not claustrophobic, no needles, only some noise. I said I would be glad to do it. They were right, lots of noise but no other discomforts. About a week later, a physician called to tell me that they found something strange on my brain. I went back to the physician and came away with a definite diagnosis of multiple sclerosis (MS). I launched a search for information, this being pre-internet, I went to libraries and contacted the National Multiple Sclerosis Society (www.nmss.org ).
By June of 2006 I had retired on disability from my position as a Science Librarian and worked from home as an editor and writer. I attended a meeting of the Outdoor Writers Association of America (www.owaa.org ). I was interested in writing for children by this time and I attended a session given by the renowned children’s author, Kathleen Kudlinski (www.kathleenkudlinski.com ). Her one piece of advice (among others) that I took away from her presentation was: “Write what you know.”
In October 2007, after spending over a year researching and learning about writing for children, I asked myself, “What do I know?” It came to me quickly, I know about MS. I have been interested in health issues and have read quite extensively, especially about plagues and infectious diseases. But also about MS, I have an extensive library about the disease and I have reviewed books on the subject for Library Journal.

Now in it’s second edition.

Interim Results Reported from Clinical Trial of Stem Cell Transplantation in People with Relapsing-Remitting MS

A nationwide team of researchers report on interim results from a small, five-year study of transplantation of the individuals’ own hematopoietic (blood cell-producing) stem cells combined with high-dose immunotherapy in 24 people with relapsing-remitting MS. This procedure aims at “rebooting” the immune system to prevent MS immune attacks against the brain and spinal cord. At three years, 78.4% of participants experienced no new disease activity. When this trial has completed its five-year duration, it will be an important addition to research needed to determine whether this approach to stem cell transplantation is safe and effective in people with MS. Richard A. Nash, MD (Colorado Blood Center Institute) and colleagues report in JAMA Neurology (Published online December 29, 2014). This study was sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Background: One type of procedure that has been explored for many years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.
In HSCT, these stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced back to the individual’s bloodstream. The new stem cells migrate to the bone marrow and over time produce new cells. Eventually they repopulate the body with immune cells. The goal of this currently experimental procedure is that the new immune cells will no longer attack myelin or other brain tissue, providing the person, what is hoped to be, a completely new immune system.
The Study: Investigators enrolled 25 people who had experienced an MS relapse involving loss of neurologic function while taking disease-modifying therapies during the previous 18 months. Participants received HSCT along with high-dose immunosuppressive therapy (a regimen of treatments that profoundly suppress the immune system), and followed for five years. The primary endpoint of this study is whether participants experience “event-free survival,” meaning that they did not die or have an increase in disease activity. Disease activity is defined as any one of the following outcomes occurring: confirmed loss of neurologic function, clinical relapse, or new lesions observed on MRI scans. The current publication presents a planned analysis after three years of follow up.
Results: One individual experienced a pulmonary embolism induced by heparin (administered as part of stem cell collection), and withdrew from the study. Event-free survival at three years was 78.4%, down from 95.8% after one year. Treatment failed in five individuals. Scores on clinical scales measuring disease activity and quality of life, including the EDSS, improved significantly at three years after HSCT. Immune system analysis showed prolonged depletion of the immune cells that drive the immune attack, indicating that the immune system was indeed “rebooted.”
Two deaths occurred, one from complications due to MS progression and another due to asthma. One person experienced an MS attack, an individual who had not complied with a prednisone regimen designed to reduce this risk during collection of stem cells. There were 130 adverse events that were severe or life-threatening, mostly cytopenias (blood cell reductions) and infections.
Comment: Rigorous clinical trials of stem cell therapies are crucial to determining their safety and effectiveness in people with MS. “We look forward to seeing the completed results of this important study,” says Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. “There are significant risks involved in hematopoietic stem cell transplantation, and it’s important to ensure that this will be a safe solution for people with MS, with significant clinical benefit.”
With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, the National MS Society believes that the potential of all types of cell therapies must be explored. The Society is currently supporting 15 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 70 stem cell studies over the past 10 years.

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