Treating Orally Earlier

News:

Top-line results of the TOPIC (Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis) trial were release today, April 25, 2013 and I had the opportunity to interview Dr. Aaron E. Miller (Medical Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center) about the study, its results and his major takeaway messages.


Aubagio (teriflunomide) becomes the first and only oral medication for MS (multiple sclerosis) that also reduces the risk of conversion from a single demyelinating attack (clinically isolated syndrome or CIS)  to a second attack (MS) -- a place previously held only by the self injectable medications.

TOPIC was similar in design to the other CIS trials -- see the study design at: http://www.clinicaltrials.gov/ct2/show/NCT00622700?term=topic+teriflunomide&rank=1

There were no unexpected safety or tolerability concerns and the dose response was consistent to what has been seen in trials of Aubagio for MS (TEMSO, TOWER and TENERE). Patients receiving Aubagio 14 mg orally daily had a 43% reduction n the risk of conversion to clinically definite MS (CDMS) compared to placebo (fake pill), over the two-year study period (p=0.0087), while those receiving 7 mg orally daily has a 37% reduction in the risk of conversion to CDMS compared to placebo.
 
Dr. Miller concluded that it is "important to treat early before a definitive diagnosis of MS can be made."
  

- Dr. Daniel Kantor, MD
  Medical Director 
  Neurologique 

   info@neurologique.org 
   www.neurologique.org

BiG News for MS: 3rd oral disease modifying drug gains FDA Approval

Breaking News:

Tecfidera (BG00012) is FDA approved for relapsing forms of MS

In 1992 we had 0 medications FDA approved for the reduction of relapses and/or disability. Since the Betaseron/Betaferon (Interferon beta-1b under the skin every other day) lottery in 1993, Tecfidera (dimethyl fumarate) becomes the 10th branded MS disease modifying agent approved for use by the FDA (U.S. Food and Drug Administration) and 3rd oral MS DMA/DMD/DMT (disease modifying agent/drug/therapy).

Tecfidera (BG12) is taken orally twice a day to try to prevent MS relapses and disability. Like every medication, it is not right for everyone.

If you are interested in Tecfidera or any of the MS DMDs (Aubagio, Avonex, Betaseron, Copaxone, Extavia, Gilenya, Novantrone, Rebif, Tysabri), talk to your neurologist.
 
- Dr. Daniel Kantor, MD
  Medical Director
  Neurologique

  info@neurologique.org
  www.neurologique.org

Sports related concussion guidelines interview

Dr. Kantor interviews Dr. Giza, the lead author on the new AAN concussion guidelines.

When in doubt, sit them out!

-  Daniel Kantor, MD
   Medical Director
   Neurologique

   President
   Florida Society of Neurology

   Chair
   Subcommittee on Concussion
   Sports Medicine Advisory Committee
   Florida High School Athletics Association

   info@neurologique.org
   www.neurologique.org

New Concussion Guidelines

Sports related concussions are traumatic brain injuries.

Today (03/18/2013), the American Academy of Neurology (AAN) released updated concussion guidelines.

According to the guideline:

• Among the sports in the studies evaluated, risk of concussion is greatest in football and rugby,
followed by hockey and soccer. The risk of concussion for young women and girls is greatest in
soccer and basketball.

• An athlete who has a history of one or more concussions is at greater risk for being diagnosed
with another concussion.

• The first 10 days after a concussion appears to be the period of greatest risk for being diagnosed
with another concussion.

• There is no clear evidence that one type of football helmet can better protect against concussion
over another kind of helmet. Helmets should fit properly and be well maintained.

• Licensed health professionals trained in treating concussion should look for ongoing symptoms
(especially headache and fogginess), history of concussions and younger age in the athlete. Each
of these factors has been linked to a longer recovery after a concussion.

• Risk factors linked to chronic neurobehavioral impairment in professional athletes include prior
concussion, longer exposure to the sport and having the ApoE4 gene.

• Concussion is a clinical diagnosis. Symptom checklists, the Standardized Assessment of
Concussion (SAC), neuropsychological testing (paper-and-pencil and computerized) and the
Balance Error Scoring System may be helpful tools in diagnosing and managing concussions but
should not be used alone for making a diagnosis.


Signs and symptoms of a concussion include:

• Headache and sensitivity to light and sound

• Changes to reaction time, balance and coordination

• Changes in memory, judgment, speech and sleep

• Loss of consciousness or a “blackout” (happens in less than 10 percent of cases)

The guideline states that while an athlete should immediately be removed from play following a
concussion, there is currently insufficient evidence to support absolute rest after concussion. Activities that do not worsen symptoms and do not pose a risk of repeat concussion may be part of concussion management.

The guideline is endorsed by the National Football League Players Association, the American Football Coaches Association, the Child Neurology Society, the National Association of Emergency Medical Service Physicians, the National Association of School Psychologists, the National Athletic Trainers Association and the Neurocritical Care Society.

When in doubt, sit them out!

- Daniel Kantor, MD
  Medical Director
  Neurologique

   President
   Florida Society of Neurology

   Chair
   Subcommittee on Concussion
   Sports Medicine Advisory Committee
   Florida High School Athletics Association

   info@neurologique.org
   www.neurologique.org

Initiating a low dose class Ia anti-arrhythmic(dextromethorphan/quinidine) in fingolimod-treated patients may be safeand effective: The first case series

 Initiating a low dose class Ia anti-arrhythmic (dextromethorphan/quinidine) in fingolimod-treated patients may be safe and effective: The first case series

ECTRIMS 2012 (Lyon, France)

Poster 529: Thursday, October 11, 2012, 15:30 - 17:00 




Click on poster (below) to download:

Background:

Recent safety concerns regarding the risk for bradyarrhythmia with fingolimod has resulted in U.S. Food and Drug Administration (FDA) changes to the package insert (PI) for the only oral MS disease modifying drug. Previously the PI listed no contraindications, while the 04/2012 version lists treatment with Class Ia anti-arrhythmic drugs among the new contraindications. Fixed dose dextromethorphan/quinidine (DM/Q) is FDA approved for the treatment of pseudobulbar affect (PBA), which is increasingly recognized as a common MS symptom. Quinidine at very low doses (10 mg twice a day) blocks CYP2D6 metabolism of DM, thus allowing this NMDA receptor antagonist and sigma-1 agonist to enter the central nervous system and exert its therapeutic effect. Qunidine causes dose-dependant QTc (corrected Q-T interval) prolongation, but the doses of Q used in the combination treatment for PBA is over 10-fold lower than the doses used for cardiac arrhythmias.

Rationale:

Despite the unlikelihood of any interaction between fingolimod and fixed dose DM/Q for PBA, fingolimod’s PI change, no longer allows concomitant treatment with these medications. Since no patients in the pivotal phase III trials for either medication were treated with the other, the current study is aimed at exploring the experience of a single MS Center with concomitant use of these medications, prior to the PI update in April 2012.

Methods:

Retrospective case series of six MS patients at a single MS Center treated with concomitant fingolimod and fixed dose DM/Q.

Results:

The mean length of time between starting fingolimod and starting DM/Q was 5 months (range: 1 – 8). There were no symptomatic bradycardias during either the first dose administration of fingolimod or subsequent to the initiation of DM/Q. Two weeks after initiation of DM/Q, the median decrease in heart rate and increase in QTc was 7 bpm and 14.5 msec (and QTc was never greater than 427 msec). Aside from improvement in their PBA, the following other improvements were reported with initiation of DM/Q: improved cognition, concentration, energy and initiation/completion of tasks, with reduction in spasticity, fatigue and feeling of being overwhelmed from pain.

Conclusion:

Initiating DM/Q in fingolimod-treated patients may be safe and effective. PBA is a potentially disabling MS symptom and there is a need to clarify whether the recent change to fingolimod’s PI should exclude concomitant treatment with DM/Q. Further controlled safety trials of concomitant fingolimod and DM/Q is needed.

- Dr. Daniel Kantor, MD
  Medical Director
  Neurologique

  info@neurologique.org
  www.neurologique.org