Current therapies

The current drug therapies for MS are dominated by recombinant forms of b-interferons.   Betaseron and Avonex were introduced in the mid 1990s, followed by Rebif in 2002. A review of clinical trial data in RR-MS revealed that their effect on exacerbations and disease progression was modest. Similarly, Glatiramer (Copaxone), which is a random polymer composed of four amino acids that are found in MBP, did not show any beneficial effect on disease progression or substantially affect the risk of clinical relapses. However, a further review of the clinical trial literature, established that the interferons and Glatiramer delayed conversion from CIS to clinically definite MS.

 

The immunosuppressant Novantrone (Mitoxantrone) has only partial efficacy and toxic side-effects means its use is restricted to those with  evidence of worsening disability and its exposure is carefully controlled and severely limited.

 

A more recent immuno-modulatory drug is Tysabri, which contains natalizumab - a humanized monoclonal antibody (mAb) to a4-b1 integrin, which blocks the endothelial transmigration of lymphocytes into the CNS. In two clinical trials, Tysabri was shown to reduce relapses to an extent that is as good as, if not greater than, that for other approved MS therapies and slowed the progression of disability in people with relapsing-remitting MS. It was therefore approved for first-line treatment of patients with "aggressive" MS (with frequent exacerbations) and for second-line treatment after failure of b-interferon. However, Tysabri’s human use was suspended in 2005 because it was implicated in three cases of progressive multifocal leukoencephalopathy (PML), a rare and usually fatal viral disease that is characterized by progressive damage white matter. As PML was evident in people receiving both Tysabri and Avonex, approval was subsequently given for the reintroduction, but as a monotherapy. The subsequent emergence of two new cases of PML in two patients receiving Tysabri alone casts further doubt on the risk/benefit ratio of this antibody therapy.

 

FDA approved drugs for the treatment of multiple sclerosis

Brand (and

generic) name

Year of FDA

approval

Mechanism

of Action

Dosing regimen (dose)
Betaseron (b- interferon) 1993 Suppression of Th1 and enhancement of Th2 immune response Every other day; subcutaneous (250 mg)
Avonex (b- interferon) 1996 Suppression of Th1 and enhancement of Th2 immune response Once a week; intramuscular (30 mg)
Copaxone (copolymer-1; glatiramer acetate) 1996 Tolerization with myelin-like antigens; modulates activity of autoreactive T cells Every day; subcutaneous (20 mg)
Novantrone (mitoxantrone) 2000 Cytotoxic antibiotic (intercalating agent and topoisomerase II inhibitor)

Four times a year by iv

infusion in a medical facility. The lifetime cumulative dose is limited to 8–12 doses over 2–3 years (140 mg).
Rebif (b- interferon) 2002 Suppression of Th1 and enhancement of Th2 immune response

Three times a eek;

subcutaneous injection (44 mg)

Tysabri (natalizumab) 2006

A humanized mAb to α4β1 integrin

Every four weeks by iv