What are the approved indications for natalizumab (Tysabri) 150 mg/mL injection (2 × 1 mL syringes) compared to the 300 mg/15 mL vial?

Natalizumab (Tysabri) Approved Indications and Formulations

Natalizumab is FDA-approved for relapsing forms of multiple sclerosis (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease) and for moderately to severely active Crohn's disease; both the 150 mg/mL syringe formulation and the 300 mg/15 mL vial formulation deliver the same 300 mg therapeutic dose and are bioequivalent with identical approved indications. 1, 2, 3

Primary Approved Indications

Multiple Sclerosis

• Natalizumab is indicated for relapsing-remitting multiple sclerosis (RRMS) to reduce the frequency of clinical relapses and delay the accumulation of physical disability. 2, 3, 4
• The drug significantly reduces annualized relapse rate (hazard ratio 0.47,95% CI 0.39-0.55) and sustained disability progression (hazard ratio 0.67,95% CI 0.52-0.88) at 2 years compared to placebo. 3
• Natalizumab reduces MRI disease activity, including new or enlarging T2 lesions (RR 0.49,95% CI 0.45-0.53) and gadolinium-enhancing T1 lesions (RR 0.12,95% CI 0.09-0.17). 3

Crohn's Disease

• Natalizumab is approved for inducing and maintaining clinical response and remission in adults with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional therapy and TNF-α inhibitors. 5
• For induction of remission in Crohn's disease, natalizumab demonstrates efficacy with RR 0.88 (95% CI 0.82-0.96) compared to placebo. 5
• For maintenance of remission, natalizumab shows RR 0.58 (95% CI 0.48-0.70) compared to placebo at one year. 5

Formulation Equivalence

Dosing and Administration

• Both formulations deliver the standard therapeutic dose of 300 mg administered intravenously every 4 weeks. 2, 3
• The 150 mg/mL formulation in 2 × 1 mL syringes provides 300 mg total dose (2 syringes × 150 mg each). 2
• The 300 mg/15 mL vial formulation provides 300 mg in a single 15 mL vial (concentration 20 mg/mL). 2
• There is no clinical difference in efficacy, safety, or monitoring requirements between the two formulations—they are simply different delivery systems for the identical therapeutic dose. 3

Critical Safety Considerations

Progressive Multifocal Leukoencephalopathy (PML) Risk

• The most serious safety concern with natalizumab is PML, a potentially fatal opportunistic brain infection caused by JC virus reactivation, which requires mandatory risk stratification and monitoring regardless of formulation used. 5, 6, 7, 4

Risk stratification is based on three factors: 5, 6

• JC virus (JCV) antibody status and index value
• Duration of natalizumab therapy (risk increases significantly beyond 24 months)
• Prior immunosuppressant use

PML risk estimates by category: 5, 6

• JCV antibody-negative: approximately 1 in 10,000
• JCV antibody-positive with index ≤1.5: approximately 1 in 5,882
• JCV antibody-positive with index >1.5: approximately 1 in 855 overall, increasing to 1 in 113 during months 25-48 of therapy

Mandatory Monitoring Protocol

Baseline assessment (before starting therapy): 6, 1

• JCV antibody testing with index value
• Baseline brain MRI (T2, DWI, FLAIR sequences minimum)

Ongoing monitoring (after 12 months): 5, 6, 1

• JCV antibody-negative patients: retest every 6 months to detect seroconversion; annual MRI surveillance
• JCV antibody-positive with index ≤1.5: retest index every 6 months; MRI every 6 months minimum after 18 months of treatment
• JCV antibody-positive with index >1.5: MRI every 3-4 months after 18 months of treatment
• All safety MRIs must be performed and reported by a neuroradiologist or radiologist trained in PML identification

Critical monitoring intensification points: 6, 1

• At 18 months: reassess risk stratification and intensify MRI monitoring based on JCV status
• At 24 months: greatest increase in PML risk occurs, requiring explicit discussion about continuation
• Patients with prior immunosuppressant use who are JCV-positive and beyond 2 years of therapy should default to 3-4 monthly MRI frequency regardless of antibody index

Additional Safety Considerations

Hepatitis B Reactivation Risk

• Natalizumab is classified as a B-cell depleting agent associated with high risk (≥10%) of hepatitis B reactivation in HBsAg-positive patients. 5
• In HBsAg-negative/anti-HBc-positive patients, natalizumab carries high risk (≥10%) for hepatitis B reactivation. 5
• Hepatitis B screening and prophylactic antiviral therapy should be considered before initiating natalizumab in at-risk populations. 5

Common Pitfalls to Avoid

• Never assume that switching between formulations (syringe vs. vial) changes the indication, dosing schedule, or monitoring requirements—they are therapeutically identical. 2, 3
• Do not reduce monitoring frequency based solely on absence of symptoms, as MRI evidence of PML may appear 3-6 months before symptom onset. 5, 6
• Clinical vigilance cannot be replaced by testing schedules; any new neurological symptoms warrant immediate evaluation regardless of scheduled monitoring intervals. 6, 1
• Never continue natalizumab beyond 24 months without explicit discussion of escalating PML risk and documented shared decision-making. 6, 7