THERAPEUTICS

Brands

• Tysabri, Antegren

Generic?

• No

Class

• Immunosuppressant

Commonly Prescribed for

(FDA approved in bold)

• As monotherapy for reducing neurological disability or relapses in patients with progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS)

• Crohn's disease (adults)

How the Drug Works

• Natalizumab is a monoclonal antibody that binds to the α4 integrin chain of the very late activation antigen (VLA)-4 adhesion molecule and blocks T-cell migration and costimulatory activating signals. These receptors include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium

• Disruption of these interactions prevents migration of leukocytes across the BBB and reduces plaque formation as measured by MRI. It does not affect the absolute neutrophil count

How Long Until It Works

• Months to years. In trials treated patients had fewer relapses up to 2 years

If It Works

• Continue to use until ineffective. Screen for AEs and consider periodic (3–6 months) monitoring of JC virus antibody status in patients continuing treatment

If It Doesn't Work

• For patients failing first-line agents (interferons, glatiramer) and with frequent relapses (measured by clinical outcome and MRI accumulation of lesions), consider using mitoxantrone or new oral agents such as fingolimod, monthly methylprednisolone, or pulse cyclophosphamide

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Acute attacks are often treated with glucocorticoids, especially if there is functional impairment due to vision loss, weakness, or cerebellar symptoms

• Treat common clinical symptoms with appropriate medication for spasticity (baclofen, tizanidine), neuropathic pain, and fatigue (modafinil)

• The SENTINEL study showed that adding natalizumab to interferon-β (INFβ)-1a decreases clinical relapses, MRI measures of disease severity and disability compared to INFβ alone, but did not compare this combination to natalizumab alone. Given that combination therapy may increase risk of adverse events, combination therapy is not recommended at this time

Tests

• MRI and serial exams to monitor disease activity. Anti-JC virus antibody prior to therapy and periodically during treatment