Details of PML Death to be Added to Tecfidera™ Prescription Label.
The U.S. Food and Drug Administration (FDA) issued a warning that a patient with multiple sclerosis (MS) who was being treated with Tecfidera (dimethyl fumarate), developed a rare and serious brain infection called progressive multifocal leukoencephalopathy (PML), and later died. As a result, information describing this case of PML is being added to the Tecfidera drug label. Patients taking Tecfidera should contact their health care professionals right away if they experience symptoms that concern them, such as new or worsening weakness; trouble using their arms or legs; or changes to thinking, eyesight, strength or balance. Health care professionals should stop Tecfidera if PML is suspected.
The patient who died was not taking any other drugs that affect the immune system or drugs that are thought to be associated with PML. This is the only confirmed case of this rare and serious brain infection reported in patients taking Tecfidera.
PML is a rare and serious brain infection caused by the John Cunningham (JC) virus. The JC virus is a common virus that is harmless in most people but can cause PML in some patients who have weakened immune systems. Symptoms of PML are diverse and may include progressive weakness on one side of the body, clumsiness, vision problems, confusion, and changes in thinking, personality, memory, and orientation. The progression of deficits can lead to severe disability or death.
The drug manufacturer, Biogen Idec, notified FDA when the MS patient died after developing PML. The patient had taken Tecfidera for more than four years. Prior to developing PML, the patient had a very low number of lymphocytes, a type of white blood cell, in her blood. Reduced lymphocyte counts can weaken the immune system, which increases the risk for PML. It is unknown whether the low lymphocyte count contributed to the development of PML in this patient, or if low lymphocyte counts are a risk factor for PML development in Tecfidera-treated patients.
FDA Drug Safety Communication: FDA warns about case of rare brain infection PML with MS drug Tecfidera (dimethyl fumarate). US Food and Drug Administration, November 25, 2014. Accessed at http://www.fda.gov/Drugs/DrugSafety/ucm424625.htm
FDA Reverses Previous Rejection and Approves MS Drug Lemtrada™.
The FDA approved Lemtrada™ (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
The FDA approval of Lemtrada is based on two pivotal randomized Phase III open-label rater-blinded studies comparing treatment with Lemtrada to Rebif® (high-dose subcutaneous interferon beta-1a) in patients with relapsing remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada was first approved in September 2013 in the European Union and is approved in more than 40 countries.
In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; however, the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a. The clinical development program for Lemtrada involved nearly 1,500 patients with more than 6,400 patient-years of safety follow-up.
Only available through a restricted distribution program, Lemtrada has a unique dosing and administration schedule of two annual treatment courses. The first treatment course is administered via intravenous infusion on five consecutive days, and the second course is administered on three consecutive days, 12 months later.
The Lemtrada label includes a boxed warning noting a risk of serious, sometimes fatal autoimmune conditions, serious and life-threatening infusion reactions, and an increased risk of malignancies including thyroid cancer, melanoma and lymphoproliferative disorders.
The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Other serious side effects associated with Lemtrada include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis.
Genzyme’s Lemtrada Approved by the FDA [Press Release]. Genzyme - A Sanofi Company, November 14, 2014. Accessed at http://news.genzyme.com/press-release/genzymes-lemtrada-approved-fda
New Italian Study: Azathioprine is Not Inferior to Beta Interferon in Treating RRMS.
Azathioprine (AZA) has been used to treat relapsing-remitting multiple sclerosis for almost 30 years in many countries. However its efficacy was usually considered marginal and following approval of beta interferon (IFN) treatments for relapsing-remitting MS, it was no longer recommended as first line treatment. To compare the efficacy of azathioprine with that of currently available beta interferons in RRMS, a multi-center, randomized, controlled, single-blind, non-inferiority trial was conducted in 30 MS centers in Italy.
Eligible patients (n=150) who had experienced more than two relapses in the previous 2 years were randomly assigned to AZA (n=77) or IFN (n=73). Study outcome measures were annualized relapse rate (ARR) over 2 years and the number of new brain MRI lesions.
At 2 years, clinical evaluation was completed in 127 patients in the AZA (n=62) and IFN (n=65) groups with annualized relapse rates of 0.26 and 0.39, respectively. Non-inferiority analysis showed that azathioprine was at least as effective as beta interferon (p<0.01). MRI outcomes were analyzed in 97 patients in the AZA (n=50) and IFN (n=47) groups with annualized new T2 lesion rates of 0.76 and 0.69, respectively. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p=0.03) in the azathioprine group compared to the IFN group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year.
The results of this study indicate that efficacy of the oral medication, azathioprine, is not inferior to that of beta interferon injectable medications for patients with relapsing-remitting multiple sclerosis. Researchers suggest that azathioprine may represent an alternative to interferon treatment, while the different side effect profiles of both medications should to be taken into account.
Massacesi L, Tramacere I, Amoroso S, Battaglia MA, Benedetti MD, et al. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial. PLoS One. 2014 Nov 17;9(11):e113371. doi: 10.1371/journal.pone.0113371. eCollection 2014.
Other Studies of Interest:
Cramer H, Lauche R, Azizi H, Dobos G, Langhorst J. Yoga for Multiple Sclerosis: A Systematic Review and Meta-Analysis. PLoS One. 2014 Nov 12;9(11):e112414. doi: 10.1371/journal.pone.0112414. eCollection 2014.
Fling BW, Dutta GG, Schlueter H, Cameron MH, Horak FB. Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis. Front Hum Neurosci. 2014 Oct 20;8:814. doi: 10.3389/fnhum.2014.00814. eCollection 2014.
Kremer TR, Van Dillen LR, Wagner JM. Dynamometer-based measure of spasticity confirms limited association between plantarflexor spasticity and walking function in persons with multiple sclerosis. J Rehabil Res Dev. 2014;51(6):975-84. doi: 10.1682/JRRD.2013.08.0186.
Sandry J, Genova HM, Dobryakova E, DeLuca J, Wylie G. Subjective cognitive fatigue in multiple sclerosis depends on task length. Front Neurol. 2014 Oct 27;5:214. doi: 10.3389/fneur.2014.00214. eCollection 2014.
Published On: November 26, 2014