Betaseron / Extavia

Interferon Beta 1a

THERAPY

Coverage

Protocols

Before Initiation of Therapy :

Negative pregnancy test and counsel with regards to contraception
CBC, liver enzymes, bilirubin, TSH,
HBsAg, anti-HBc, anti-HBs, Hepatits C, HIV, VZV serology
Vaccination status verified and updated if necessary
Pneumococcus and Haemophilus influenza type B vaccines

Schedule for Dose Titration

The titration period may be adjusted if any significant adverse reaction occurs.

In the secondary-progressive MS study, patients initiated treatment with half the dose (4 MIU SC every other day) for a period of 2 weeks prior to escalating to the recommended dose of 8 MIU (SC every other day).

Monitoring During Therapy :

Discontinue Therapy :

ALT>5X ULN or jaundice
Nabs (+) (2 -6 %)
Severe thrombocytopenia especially in setting of fever and encephalopathy (R/O TTP)
Depression or suicidal ideation
Unexplained cardiomyopathy with /out congestive heart failure
Pregnancy
Seizure

Studies

(Some studies only include abstracts)

Title

Benefit

Source

JAMA Neurology

Date Published

9/1/2007

IFNB Multiple Sclerosis

NCBI

4/4/1993

The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group

Neurology

7/4/1995

European

The Lancet

11/7/1998

Product Monograph

Specific Concerns

Storage :

Should be stored in a refrigerator . Extremes in temperature and exposure to ligth should be avoided

Patient Selection :

Should be used with caution in patients with prior seizure disorder, liver disease, ongoing depression or concomitantly with other potentially liver toxic therapies

Adverse Events :

Most frequent adverse event is flu like symptoms (76%) and injections site reactions (85%) . The former tends to diminish in severity and frequency with time (10% after 3 years ).
Decreased peripheral blood counts in all cell lines, including very rare pancytopenia and thrombocytopenia have been reported from post-marketing experience
Elevated liver enzymes from hepatic injury or hepatitis including hepatic failure have been reported
Can lead to autoimmune disorders such as drug induced SLE, autoimmune hepatitis, hyper or hypothyroidism, thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. These events can may occur after several weeks to several years after starting treatment with interferon beta.
Anaphylaxis has been reported as a rare complication. Other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria
Pancreatitis has been observed with BETASERON use, often associated with hypertriglyceridemia
Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN) have been reported during treatment with interferon-beta products.
Rare cases of secondary systemic capillary leak sydrome (Clarkson syndrome) has been reported with interferon beta administration to patients with underlying monoclonal gammopathy

Injection Site Reactions :

Injection site reaction will occur in 85% of patients. Injection site necrosis (5%) tend to occur early within the first 2-3 months of initiating therapy and rarrely extends to subcutanous fat or fascia.

Neutralizing Antibodies :

Serum neutralizing antibodies (Nabs) were reported to develop in 23 to 41% of patients. Nabs tend to occur by the end of the first year of treatment. Over the subsequent 5 year observation period, approximately 50% of these patients will revert to being Nabs negative. Nabs however have been shown, during the period of Nab positivity to impact clinical efficacy and MRI measures.

Long Term Study (BENEFIT CIS 11 yrs FU Study) :

59% of the original 468 patients were recruited. At year 11, 67% were on a DMT and more specifically only 30% were on Betaseron. No significant difference was found between early and late treatment groups with regards to EDSS, SPMS conversion rate and MRI outcomes.