Comparing Drugs for Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. MS affects the myelin coating of nerves, interrupting nerve conduction and leaving lesions that can be seen on brain scans.
Symptoms of MS can be unpredictable, and include changes in sensation, muscle weakness, and problems with balance and coordination. Symptoms may gradually develop and worsen over time, or more commonly, occur in acute attacks (relapses) followed by symptom-free periods (remissions). About 85% of patients have the relapsing-remitting form of MS (RRMS), and most cases eventually develop into a secondary progressive form (SPMS).
The management of MS includes treating symptoms (e.g. muscle relaxants for muscle spasms) and acute flare-ups (e.g. high dose steroids for sudden loss of vision). Disease-modifying drugs are used to slow the progression of MS. These drugs modify the immune response and include the β interferons (Avonex, Rebif, Betaseron, and Extavia), glatiramer acetate (Copaxone), mitoxantrone (Novantrone) and natalizumab (Tysabri).
The "Drug Class Review on Disease-modifying drugs for Multiple Sclerosis" compares the safety and effectiveness of seven drugs. A summary of the findings is below.
How do Disease-modifying Drugs compare in Multiple Sclerosis?
In patients with relapsing-remitting multiple sclerosis, Avonex is less effective than Rebif and Betaseron for preventing relapse. Fair evidence suggests that Rebif is similar to Avonex for slowing disease progression. Evidence comparing Betaseron to Avonex for preventing disease progression was conflicting, with one trial showing Betaseron more effective for slowing disease progression, but no difference between the drugs in measures of disability.
No differences were found between Copaxone and Rebif or Betaseron in either relapse rates or disease progression.
Direct comparisons are lacking in other types of multiple sclerosis. Natalizumab and mitoxantrone have not been directly compared to other disease-modifying drugs.
How do Disease-modifying Drugs compare in Clinically Isolated Syndrome?
Compared to placebo, the following drugs were more effective at reducing the chances of a clinically isolated syndrome converting into multiple sclerosis: Avonex, Betaseron, Copaxone, and Rebif.
There are no studies of Novantrone or Tysabri in patients with a clinically isolated syndrome.
How do Disease-modifying Drugs compare in Safety?
Interferons appear to share a similar rate of adverse events. Increases in liver enzymes are common, but most are transient and asymptomatic. Avonex had the lowest rate of injection site reactions (9%, compared to ~ 60% for Betaseron and Rebif) but flu-like symptoms were about twice as common.
Data are limited for other adverse events, such as for depression, but suggest a lower rate of depression in patients taking Rebif compared with other interferons. Mitoxantrone has been linked with acute leukemia (2 in 1620 patients) and cardiotoxicity (incidence 0.15%), and natalizumb has been linked with progressive multifocal leukoencephalopathy (incidence 0.001%).
How do Patient Factors affect the Safety and Effectiveness of Disease-modifying Drugs?
Observational studies of women taking beta interferons or glatiramer in pregnancy did not find an increase in risk of adverse events, but there is not enough evidence to determine the safety of multiple sclerosis drugs in pregnancy.
One analysis found that African-American patients were more likely to experience exacerbations with Avonex and Rebif compared to white patients.
There is some evidence that response to beta interferons and glatiramer differs in men and women, but there is no evidence that this difference favors one product over another.
Drugs Included in this Review
|Generic Name||Trade Names|
|Interferon β 1a||Avonex
|Interferon β 1a||Rebif|
|Interferon β 1b||Betaseron|
|Interferon β 1b||Extavia|