3.26.11

The other day I had an appointment with my new neurologist.  As many of you may know, my previous neurologist, Dr. Hillel Panitch, died in December of Stage 4 Melanoma.

With the new doctor, Dr. Applebee, I was given a full neuro exam [which you all know now what that consists of :)].  I'm also going to be part of a trial which looks for the marker for the JC virus which can make patients taking Tysabri more prone to a potentially fatal brain disease.

Section Contents Menu
Drug Safety and Availability
Postmarket Drug Safety Information for Patients and Providers


Index to Drug-Specific Information Approved Risk Evaluation and Mitigation Strategies (REMS) Postmarketing Safety Evaluation of New Molecular Entities: Final Report Drug Safety Information for Healthcare Professionals- FDA Drug Safety Communication: Risk of Progressive Multifocal Leukoencephalopathy (PML) with the use of Tysabri (natalizumab)


Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals

Data Summary


Safety Announcement


[02-05-2010] The U.S. Food and Drug Administration (FDA) is alerting the public that the risk of developing progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection associated with the use of Tysabri (natalizumab), increases with the number of Tysabri infusions received. This new safety information, based on reports of 31 confirmed cases of PML received by the FDA as of January 21, 2010, will now be included in the Tysabri drug label and patient Medication Guide (see Data Summary for additional information).


Tysabri was approved by the FDA in November 2004 for the treatment of relapsing forms of multiple sclerosis (MS). Tysabri is also approved by FDA for treating moderately to severely active Crohn's disease.


Since 2006, Tysabri has only been available through a risk minimization plan called Tysabri Outreach Unified Commitment to Health (the TOUCH™ Prescribing Program). The program, developed by the FDA and the manufacturer of Tysabri, Biogen-Idec, is intended to make sure that healthcare professionals and patients understand the benefits and potential risks associated with the use of Tysabri, including the risk of PML.Under the TOUCH™ program, every patient who receives Tysabri is closely monitored for the occurrence of PML and other serious opportunistic infections. For additional information about the TOUCH™ program click here1.


Based on the available information, the FDA believes that the clinical benefits of Tysabri continue to outweigh the potential risks. Revisions to the drug label and patient Medication Guide, with the continued use of the TOUCH Prescribing Program, are intended to maximize the safe use of Tysabri and the identification of new PML cases.


Additional Information for Patients


Tysabri is a medication that has been associated with PML and the risk of developing this disease increases with the number of Tysabri infusions received.


PML is a rare infection of the brain caused by the JC virus, which is a common virus often acquired during childhood. Most adults have been infected with JC virus, but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) causes it to be reactivated. Once reactivated, the virus may infect the brain and cause PML.


People with a weakened immune system or people taking drugs that suppress their immune system (immunosuppressants) are most likely to get PML. Tysabri is an immunosuppressant medication.


The symptoms of PML may begin gradually, usually worsen rapidly, and vary depending on which part of the brain is infected. These symptoms may include difficulty with walking and other movements, decline in mental function, and problems with vision and speaking. Rarely, headaches and seizures occur. Symptoms of PML may be similar to multiple sclerosis (MS).


If PML is suspected, Tysabri treatment should be stopped and not resumed until further clinical evaluation is performed.


When patients have the clinical symptoms of PML, a PML diagnosis is made by an MRI of the brain and confirmation of the presence of JC virus in the cerebrospinal fluid.


Cases of Immune Reconstitution Inflammatory Syndrome (IRIS) have been reported after stopping Tysabri because of PML. IRIS is a condition that can occur after discontinuing immunosuppressant medications. During immune system recovery, patients can experience a severe inflammatory response to an infection and their symptoms can get worse, sometimes after a period of improvement.



Data Summary



The FDA continues to receive reports of PML in patients receiving Tysabri in the United States and overseas. Tysabri, an immunosuppressant medication, was first approved by the FDA in November 2004 for the treatment of relapsing forms of multiple sclerosis (MS). In February 2005, the marketing of Tysabri was suspended by the manufacturer after three patients in clinical trials (two patients in MS trials and one in a Crohn's disease [CD] trial) developed PML. In June 2006, the FDA approved an application for the re-marketing of Tysabri as monotherapy for the treatment of patients with relapsing forms of MS.


Tysabri is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate MS therapy. In January 2008, Tysabri was also approved for inducing and maintaining a clinical response and remission in patients with moderately to severely active CD who have had an inadequate response to, or are unable to tolerate, conventional CD therapies.


Since July 2006 (when marketing resumed) through January 21, 2010, there have been 31 confirmed cases of PML worldwide in patients using Tysabri. Of these 31 case reports, 10 were from patients in the U.S. As of January 21, 2010, eight patients have died. In all cases, patients were receiving Tysabri as monotherapy for the treatment of MS. There have been no postmarketing reports of PML in patients treated with Tysabri for CD. In the U.S., less than 2% of Tysabri use is in patients with CD. Tysabri is not approved for CD outside of the U.S.


The risk of developing PML increases with the number of Tysabri infusions received. Tysabri is administered as a single intravenous infusion every four weeks. The overall worldwide cumulative rate of PML in patients who have received one or more Tysabri infusions is 0.5 cases of PML per 1,000 patients. Since Tysabri's re-marketing in the U.S., there have been no cases of PML in patients treated with Tysabri for less than 12 months. The overall worldwide cumulative rate of PML in patients who have received at least 24 infusions is 1.3 cases of PML per 1,000 patients. In the U.S., the cumulative rate of PML in patients who have received at least 24 infusions is 0.8 per 1,000 patients. Outside of the U.S., the cumulative rate of PML in patients who have received at least 24 infusions is 1.9 per 1,000 patients.


Approximately 66,000 people, worldwide, have received at least one dose of Tysabri since marketing resumption (through December 31, 2009). Relatively few patients have received 36 infusions or more, either in clinical trials or since marketing resumption; therefore, the magnitude of the risk of PML and other adverse events in patients who have received 36 infusions or more is not able to be well characterized.


The FDA and its international counterparts remain committed to tracking and monitoring for any change in the risk of PML associated with the use of Tysabri.


This communication is intended to increase awareness about the risk of PML in patients treated with Tysabri.At this time, the FDA believes that the clinical benefits of Tysabri outweigh its risks. Tysabri will remain available to patients through the TOUCH™ Prescribing Program. Under this program, every patient who receives Tysabri is closely monitored for the occurrence of PML and other serious opportunistic infections.

http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm199872.htm

Fortunately, I have shown no signs of having developed this scary side effect and I'm closely monitored.


Two other follow-ups to the exam were the scheduling of an MRI and a blood draw.  Right after my appointment I went down to the phlebotomy lab to have my blood drawn. 


My doctor called me a couple of days ago to let me know the results of the blood panel.  Good news was that my white blood count and my liver function are good.  The downside, or the upside, depending on how you look at it, is that the blood tests showed that my vitamin D levels are really low.  I know...shocker, seeing as where we live.  Normal levels should be between 30 and 40.  My doctor likes to see her MS patients with levels around 50.  My vitamin D level is 5.  Apparently, this can have more of an effect on me than I realized.

Vitamin D Deficiency and related symptoms



Vitamin D deficiency can cause very dangerous disorders. Vitamin D deficiency symptoms are a warning sign that let’s you know something is not quite right. You need to make sure you are getting enough vitamin D from exposure to direct sunlight, vitamin D rich food and vitamin supplements.


Vitamin D deficiency symptoms appear more as various disorders. These symptoms include:


Rickets – It is the most frequent vitamin D deficiency symptom in children. As a result of vitamin D deficiency, the bones are weakened, the bone tissue fail to mineralize leading to soft and deformed bones.


Osteoporosis – It is a similar symptom to rickets, but it is found as vitamin D deficiency symptom in adults. Because of the low vitamin D level in the body there is deficient calcification in bones, which become brittle and soft.


Depression – According to scientist, depression is the result of the lack of vitamin D. They argue that because of urbanization, the sunlight can’t adequately reach the skin, reducing thus the 25(OH) level in the body, causing depression. It has been also discovered that a great number of people suffer from seasonal affective disorder during the winter due to insufficient exposure to direct sunlight. The parathyroid hormone is the one causing the vitamin D deficiency symptom – depression.


Hyperparathyroidism – Results from hypocalcemia, which is a blood condition with unusually low vitamin D level, resulting in hyperparathyroidism.


Fatigue – According to old remedies, sunshine and fresh air are essential for good health. The absence of vitamin D synthesis in the morning can result in fatigue.


Obesity – Vitamin D deficiency is frequently linked to obesity, as the insufficient level of vitamin D holds back the production of hormone leptin, which regulates the fat in the body. Inadequate exposure to sunlight disrupts the normal function of the body, determining the individual to eat more than it is necessary for the body.


The list of vitamin D deficiency symptoms also includes chronic backache, cancer, chronic pain, diabetes, multiple sclerosis, heart diseases or hypertension.

I've started taking vitamin D in the hopes of boosting my levels.  I've noticed issues with depression and fatigue.  Of course, this are also symptoms of MS so I'm not helping myself any by having a vitamin D deficiency.

Hmmm...I also just noticed chronic backache (check) and multiple sclerosis (check).

Thank you for letting me vent and express myself through this venue.  I really appreciate all of you that are reading this...I am very interested in helping my friends and family undertand this disease.