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  #21  
Old 01-24-2012, 06:28 PM
TJ1 TJ1 is offline
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Default p.s.

... to add to that, I didn't want to get on a DMD halfheartedly and (like the woman flushing her shots), as a result, not be 'all in.'

Anyway...
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  #22  
Old 01-24-2012, 07:45 PM
stevema55 stevema55 is offline
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Your welcome,
Anytime you want my opinion or real-life experience feel free to contact me.
Oh, I just got email from Novartis telling me it's time to get my 3-4month blood test.

Best Regards,
Steve
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  #23  
Old 01-25-2012, 08:19 PM
stevema55 stevema55 is offline
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Default New England Journal of Medicene Gilenya Report 1-26-2012

Sorry about the Cut-n-Paste.



TEACHING TOPICS from the New England Journal of Medicine

Teaching Topics | January 26, 2012
Fingolimod in Multiple Sclerosis: What is the efficacy of oral fingolimod in treating multiple sclerosis?

Bevacizumab in Breast Cancer: What are the benefits of adding bevacizumab to anthracycline and taxane containing chemotherapy in HER2-negative early-stage breast cancer?

Teaching Topic
Fingolimod in Multiple Sclerosis
Clinical Therapeutics
Fingolimod for Multiple Sclerosis
D. Pelletier and D.A. Hafler





Multiple sclerosis is an inflammatory, central nervous system disease sharing several genetic variants with other autoimmune diseases. It affects approximately 400,000 people in the United States and 2.5 million worldwide, with a prevalence of approximately 1:1000 in Caucasian populations (female:male, >2:1). The vast majority of patients with multiple sclerosis have a relapsing form of the disease at onset (approximately 85% relapsing–remitting course). More than half of patients will accumulate sustained disability between acute attacks and transition to secondary progressive multiple sclerosis within 10 to 20 years after diagnosis.

Clinical Pearls
What is the mechanism of action of fingolimod?
Lymphocyte migration out of lymph nodes is dependent upon engagement of a G protein–coupled receptor, S1P1, found on the surface of the lymphocyte. The ligand for this receptor, the lipid sphingosine S1P, is predominantly found in the serum and lymph. Fingolimod, also known as FTY720, is structurally similar to S1P. Fingolimod is phosphorylated in vivo after oral ingestion and can then engage four of the five known S1P receptors. In lymph nodes, fingolimod initially acts as an agonist of the S1P1 receptor and then becomes a highly potent functional antagonist, leading to internalization of S1P1 receptors on lymph node T-cells. As a result, lymphocytes no longer respond to the gradient of S1P and remain sequestered in the lymph node.

What is the efficacy of oral fingolimod in treating multiple sclerosis?
The efficacy of oral fingolimod in multiple sclerosis was investigated in two large, phase 3 trials of subjects with relapsing–remitting disease. The FREEDOMS trial randomized patients to either oral fingolimod at a dose of 0.5 mg daily or 1.25 mg daily or placebo tablets for 2 years. The annualized relapse rate, the primary end point, was 0.18 with the 0.5-mg regimen, 0.16 with 1.25 mg, and 0.40 with placebo (P<0.001 for either regimen). The cumulative probability of progression based on the Expanded Disability Status Scale (confirmed after 3 months) was 17.7% with 0.5 mg of fingolimod and 16.6% with 1.25 mg of fingolimod, favoring either regimen over placebo (24.1%; P=0.03 and P=0.01, respectively). Fingolimod also reduced the number of new or enlarging T2-weighted images and gadolinium-enhancing lesions on MRI at year 2. The TRANSFORMS trial randomized patients to receive either oral fingolimod at a dose of 0.5 mg daily or 1.25 mg daily or intramuscular interferon beta-1a (30 µg) weekly for 1 year. The annualized attack rate, the primary end point, was 0.16 with the 0.5-mg regimen, 0.20 with 1.25 mg, and 0.33 in the interferon group (P<0.001 for either fingolimod regimen compared to interferon).

Morning Report Questions
Q. What are the side effects associated with use of fingolimod?
A. The most common serious adverse effects reported in this week’s issue of the Journal are cardiovascular events, including bradycardia (1 to 3%) and first- or second-degree atrioventricular block (<1%). Most of these events were asymptomatic, observed during the administration of the first oral dose, and resolved quickly within 24 hours. In addition, a dose-dependent mild increase in systolic and diastolic blood pressures was observed over 2 years. There was also a slight increase in the incidence of mild infections, mainly lower respiratory tract (bronchitis and pneumonia) and herpes virus infections. Macular edema was confirmed by ophthalmologic evaluation in less than 1% of patients. Localized skin cancer (basal-cell carcinoma and melanoma) and breast-cancer cases were more frequently reported with both high- and low-dose regimens compared to placebo. Mild dose-dependent decreases in lung function were found, and peripheral blood lymphocyte counts were reduced after the first month by approximately 75% from baseline. Asymptomatic elevations in liver enzyme levels were more frequent in subjects on fingolimod than placebo.

Q. According to the authors, when in the course of multiple sclerosis should fingolimod be used?
A. Even though fingolimod has been approved as a first-line drug for the treatment of multiple sclerosis, the authors feel strongly that this agent should be reserved as a second-line drug until further long-term safety investigations have allowed for evaluation of the risks of infectious complications and secondary malignancies. As there are a significant number of patients with multiple sclerosis who do well with first-line drugs that have minimal side effects, they feel it is prudent to initiate these drugs with the first evidence of a clinically isolated syndrome with abnormal MRI findings consistent with a demyelinating process. However, considering the apparent benefits from the greater clinical efficacy of the agents affecting T-cell migration (fingolimod and natalizumab) and the consequences of chronic central nervous system inflammation associated with multiple sclerosis, the authors recommend a relatively low threshold for initiating second-line therapies when permanent clinical signs of central nervous system injury are present. They recommend the consideration of fingolimod for patients experiencing recent (within the last year) inflammatory disease activity (one or more relapses or new white-matter lesions on MRI) or when there is evidence that alternative disease-modifying therapies have not been beneficial or are poorly tolerated. They also recommend that patients should have taken no immunosuppressive medications or received natalizumab infusion in the preceding 3 months (6 months for long-term intravenous immunosuppression such as mitoxantrone or cyclophosphamide) before initiating fingolimod.

Figure 3. Decision-Making Therapeutic Algorithm, Including Newly Approved Fingolimod, for Patients with Relapsing Forms of Multiple Sclerosis (MS).
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  #24  
Old 02-13-2012, 02:28 AM
RobDavidson RobDavidson is offline
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Hey all, I'm in San Diego CA and there's a couple of presentations on Gilenya coming up Feb 29th and March 15th here that I'm planning on going to. I'm not really looking into switching meds as I'm doing very well on Extavia but I am curious about this drug given all that has been said about it. If anybody has any questions they want me to ask the Gilenya reps post it to this thread and I'll report back.
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  #25  
Old 02-13-2012, 01:40 PM
laacevedo625 laacevedo625 is offline
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I agree. I had a very bad side effect with first dose. I feel that it should be continuous monitoring and longer monitoring. The worse of it did not start for me until the 8th hour. I was not in good shape when I was discharged at the 6th hour. Fortunately the effects passed and I was ok.
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  #26  
Old 02-13-2012, 01:42 PM
laacevedo625 laacevedo625 is offline
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Oops - somehow I replied to the wrong thread!
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  #27  
Old 04-23-2012, 08:26 AM
Melalshy Melalshy is offline
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Default Bells Palsey

Interesting, but I started Gilenya in December and just finished a bout of Bells Palsey as well. My doctor also told me it was most likely a coincidence. I was searching to see if any others had this "coincidence" and found you so I thought I'd mention it.
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  #28  
Old 04-23-2012, 08:28 AM
Melalshy Melalshy is offline
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Interesting, but I started Gilenya in December and just finished a bout of Bells Palsey as well. My doctor also told me it was most likely a coincidence. I was searching to see if any others had this "coincidence" and found you so I thought I'd mention it.
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