Select therapeutic use:

Colorectal disorders:

Indications for: TYSABRI

In moderately to severely active Crohn's disease: to induce and maintain clinical response and remission in adult patients with evidence of inflammation who have had inadequate response to or are intolerant to conventional therapy and TNF-α inhibitors.

Clinical Trials:

Crohn’s Disease

  • The approval was based on 3 randomized, double-blind, placebo-controlled trials that evaluated Tysabri in 1414 adults with moderately to severe active Crohn’s disease (CDAI ≥220 and ≤450). Concomitant inhibitors of TNF-α were not permitted. Concomitant stable doses of aminosalicylates, corticosteroids, and/or immunosuppressants (e.g., 6-mercatopurine, azathioprine, or methotrexate) were permitted, and 89% of patients continued to receive at least one of these medications.

  • In Study CD1, 896 patients were randomly assigned 4:1 to receive 3 monthly infusions of either Tysabri 300 mg or placebo. At week 10, results showed that 56% of the 717 patients receiving Tysabri were in response compared to 49% of the 179 patients receiving placebo (treatment effect: 7%; 95% CI, -1%, 16%; P =.067). In a post hoc analysis of the subset of 653 patients with elevated baseline C-reactive protein (CRP), indicative of active inflammation, 57% of Tysabri patients were in response compared to 45% of those receiving placebo (treatment effect: 12%; 95% CI: [3%, 22%]; nominal P =.01).

  • In Study CD2, 509 patients were randomly assigned 1:1 to receive 3 monthly infusions of either Tysabri 300 mg or placebo. Induction with Tysabri achieved the following clinical response and remission at weeks 8 and 12 compared with placebo, respectively:

    • Clinical Response at week 8: 56% vs 40% (treatment difference, 16%; 95% CI, 8-26)

    • Clinical Response at week 12: 60% vs 44% (treatment difference, 16%; 95% CI, 7-25)

    • Clinical Response at both weeks 8 & 12: 48% vs 32% (treatment difference, 16%; 95% CI, 7-24)

    • Clinical Remission at week 8: 32% vs 21% (treatment difference, 11%; 95% CI, 3-19)

    • Clinical Remission at week 12: 37% vs 25% (treatment difference, 12%; 95% CI, 4-21)

    • Clinical Remission at both weeks 8 & 12: 26% vs 16% (treatment difference, 10%; 95% CI, 3-18)

  • In Study CD3, maintenance therapy was evaluated in 331 patients who had a clinical response to Tysabri at both Weeks 10 and 12. Patients were re-randomly assigned 1:1 to continue receiving monthly infusions of either Tysabri 300 mg or placebo. Maintenance treatment with Tysabri achieved the following clinical response and remission at Months 9 and 15 compared with placebo, respectively:

    • Clinical Response through Month 9: 61% vs 29% (treatment difference, 32%; 95% CI, 21-43)

    • Clinical Response through Month 15: 54% vs 20% (treatment difference, 34%; 95% CI, 23-44)

    • Clinical Remission through Month 9: 45% vs 26% (treatment difference, 19%; 95% CI, 6-31)

    • Clinical Remission through Month 15: 40% vs 15% (treatment difference, 25%; 95% CI, 13-36)

Adult Dosage:

≥18yrs: Give by IV infusion over 1hr; monitor during and for 1hr post-infusion. 300mg every 4 weeks. Discontinue after 12 weeks of induction therapy if no therapeutic response, or if unable to taper off chronic concomitant steroids within 6 months of starting therapy. May continue with aminosalicylates.

Children Dosage:

<18yrs: not established.

TYSABRI Contraindications:

Progressive multifocal leukoencephalopathy (PML).

Boxed Warning:

Progressive multifocal leukoencephalopathy.

TYSABRI Warnings/Precautions:

Increased risk of PML with longer treatment duration (>2yrs), prior treatment with immunosuppressants, and/or presence of anti-JCV antibodies. Monitor for signs/symptoms of PML; withhold if develops. Test patients for anti-JCV antibody status prior to or during treatment if status unknown; patients with negative status should be retested periodically. Reevaluate periodically (at 3 months and 6 months post-infusion, every 6 months thereafter, and for at least 6 months after discontinuation). MS: obtain MRI scan prior to initiating therapy. Risk of JCV granule cell neuronopathy; manage similarly to PML if develops. Monitor for herpes encephalitis and meningitis; discontinue and treat if occurs. Refer for retinal screening if eye symptoms develop; consider discontinuing therapy if acute retinal necrosis is confirmed. Discontinue if jaundice or liver injury occurs, or if thrombocytopenia is suspected. Immunosuppression. Monitor for infections. Vaccinations. Elderly. Neonates. Pregnancy. Nursing mothers.

TYSABRI Classification:

Immunomodulator (integrin receptor antagonist).

TYSABRI Interactions:

Concomitant other immunosuppressants or TNF-α inhibitors: not recommended.

Adverse Reactions:

Headache, fatigue, arthralgia, infections, depression, pain in extremity, abdominal discomfort, diarrhea NOS, nausea, rash; immune reconstitution syndrome (monitor), hypersensitivity reactions (discontinue if occurs; do not restart), hepatotoxicity, inj site reactions, antibody formation (if persistent, may substantially reduce efficacy), changes in blood cell counts.

Note:

This product is only available through the TOUCH prescribing program. For more information call (800) 456-2255.

Drug Elimination:

  • Half-life: 11 ± 4 days (MS patients); 10 ± 7 days (CD patients).

  • Clearance: 16 ± 5 mL/hour (MS patients); 22 ± 22 mL/hour (CD patients).

REMS:

YES

Generic Drug Availability:

NO

How Supplied:

Single-use vial—1

Multiple sclerosis:

Indications for: TYSABRI

Monotherapy for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Clinical Trials:

Multiple Sclerosis

  • The approval was based on 2 randomized, double-blind, placebo-controlled trials (Study MS1 and MS2) that evaluated Tysabri in patients with MS who experienced at least 1 clinical relapse during the prior year and had a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0. In both studies, neurological evaluations were performed every 12 weeks and at times of suspected relapse. MRI evaluations for T1-weighted Gd-enhancing lesions and T2-hyperintense lesions were performed annually.

  • Study MS1 included patients who had not received any interferon-beta or glatiramer acetate for at least the previous 6 months. Patients were randomly assigned 2:1 to receive Tysabri 300mg IV infusion (n=627) or placebo (n=315) every 4 weeks for up to 28 months (30 infusions).

  • Study MS2 included patients who had experienced one or more relapses while on treatment with Avonex (Interferon beta-1a) 30mcg intramuscularly (IM) once weekly during the year prior to study entry. Patients were randomly assigned to receive Tysabri 300mg (n=589) or placebo (n=582) every 4 weeks for up to 28 months (30 infusions). All patients received Avonex 30mcg IM once weekly.

  • The primary endpoint at 2 years was time to onset of sustained increase in disability, defined as an increase of at least 1 point on the EDSS from baseline EDSS ≥ 1.0 that was sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS=0 that was sustained for 12 weeks.

  • In Study MS1, treatment with Tysabri achieved the following results at 2 years compared with placebo, respectively:

    • Percentage with sustained increase in disability: 17% vs 29% (relative risk reduction, 42%; 95% CI, 23-57)

    • Annualized relapse rate: 0.22 vs 0.67 (relative reduction, 67%)

    • Percentage of patients remaining relapse-free: 67% vs 41%

    • New or newly enlarging T2-hyperintense lesions (median): 0.0 vs 5.0

    • Gd-enhancing lesions (median): 0.0 vs 0.0

  • In Study MS2, treatment with Tysabri achieved the following results at 2 years compared with placebo, respectively:

    • Percentage with sustained increase in disability: 23% vs 29% (relative risk reduction, 24%; 95% CI, 4-39)

    • Annualized relapse rate: 0.33 vs 0.75 (relative reduction, 56%)

    • Percentage of patients remaining relapse-free: 54% vs 32%

    • New or newly enlarging T2-hyperintense lesions (median): 0.0 vs 3.0

    • Gd-enhancing lesions (median): 0.0 vs 0.0

Adult Dosage:

≥18yrs: Give by IV infusion over 1hr; monitor during and for 1hr post-infusion. 300mg every 4 weeks.

Children Dosage:

<18yrs: not established.

TYSABRI Contraindications:

Progressive multifocal leukoencephalopathy (PML).

Boxed Warning:

Progressive multifocal leukoencephalopathy.

TYSABRI Warnings/Precautions:

Increased risk of PML with longer treatment duration (>2yrs), prior treatment with immunosuppressants, and/or presence of anti-JCV antibodies. Monitor for signs/symptoms of PML; withhold if develops. Test patients for anti-JCV antibody status prior to or during treatment if status unknown; patients with negative status should be retested periodically. Reevaluate periodically (at 3 months and 6 months post-infusion, every 6 months thereafter, and for at least 6 months after discontinuation). MS: obtain MRI scan prior to initiating therapy. Risk of JCV granule cell neuronopathy; manage similarly to PML if develops. Monitor for herpes encephalitis and meningitis; discontinue and treat if occurs. Refer for retinal screening if eye symptoms develop; consider discontinuing therapy if acute retinal necrosis is confirmed. Discontinue if jaundice or liver injury occurs, or if thrombocytopenia is suspected. Immunosuppression. Monitor for infections. Vaccinations. Elderly. Neonates. Pregnancy. Nursing mothers.

TYSABRI Classification:

Immunomodulator (integrin receptor antagonist).

TYSABRI Interactions:

Concomitant other immunosuppressants: not recommended.

Adverse Reactions:

Headache, fatigue, arthralgia, infections, depression, pain in extremity, abdominal discomfort, diarrhea NOS, nausea, rash; immune reconstitution syndrome (monitor), hypersensitivity reactions (discontinue if occurs; do not restart), hepatotoxicity, inj site reactions, antibody formation (if persistent, may substantially reduce efficacy), changes in blood cell counts.

Note:

This product is only available through the TOUCH prescribing program. For more information call (800) 456-2255.

Drug Elimination:

  • Half-life: 11 ± 4 days (MS patients); 10 ± 7 days (CD patients).

  • Clearance: 16 ± 5 mL/hour (MS patients); 22 ± 22 mL/hour (CD patients).

REMS:

YES

Generic Drug Availability:

NO

How Supplied:

Single-use vial—1