Tocilizumab (Actemra®), tocilizumab-bavi (Tofidence^TM) and and tocilizumab-aazg (Tyenne®) are recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibodies that work to inhibit IL-6 mediated actions at soluble and membrane bound IL-6 receptors. Inhibiting the signaling pathway can lead to inhibition of activated T- and B-cells, lymphocytes, monocytes, and fibroblasts.

Tocilizumab (Actemra) for Intravenous (IV) Use

Tocilizumab (Actemra) IV injection may be considered medically necessary when an individual meets the criteria for ANY ONE of the following:

• Cytokine Release Syndrome (CRS):
  • The individual is two (2) years of age and older with severe or life threatening CRS induced by chimeric antigen receptor T-cell (CAR-T) therapy; or
• Giant Cell Arteritis (GCA):
  • The inidivual is 18 years of age and older for the treatment of GCA; and
  • Treatment with at least one (1) systemic corticosteriod (e.g. prednisone) was ineffective and not tolerated, or all crticosteriods are contraindicated; or
• Management of Immunotherapy-Related Toxicities:
  • For management of CAR-T related toxicities such as:
    • G2-4 CRS; or
    • G1-4 neurotoxicity as additional single-dose therapy if concurrent CRS; or
  • For management of prolonged (greater than 3 days) G1 CRS in individuals with significant symptoms and/or comorbidities; or
  • For management of immune checkpoint inhibitor-related toxicities as additional management of severe immunotherapy-related inflammatory arthritis if symptoms do not improve within 2 weeks of starting high-dose corticosteroids; or
• Juvenile Idiopathic Arthritis, Polyarticular (PJIA):
  • The individual is two (2) years of age and older with active PJIA; and
  • Treatment with at least one (1) disease modifying anti-rheumatic drug (DMARD) (e.g. methotrexate, leflunomide, sulfasalazine) was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
  • The individual requires initial biologic therapy due to involvement of high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, and/or those judged by their provider to be at high risk of disabling joint damage; or
• Juvenile Idiopathic Arthritis, Systemic (SJIA):
  • For individuals two (2) years of age and older with active SJIA; and
  • Treatment with at least one (1) non-biologic DMARD (e.g. methotrexate, leflunomide, sulfasalazine) was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
• Rheumatoid Arthritis (RA):
  • The individual is 18 years of age and older with moderately to severely active RA; and
  • Treatment with at least one (1) non-biologic DMARD (e.g. methotrexate, leflunomide, sulfasalazine) was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; and

Compendia Sources

• Tocilizumab (Actemra) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

Reauthorization Criteria (for non-oncologic indications)

Continuation of therapy with tocilizumab (Actemra) for may be considered medically necessary when the following criteria are met:

• The individual has one of the above diagnoses; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of tocilizumab (Actemra IV) not meeting the criteria as indicated in this policy is considered not medically necessary.

Tocilizumab (Actemra) for Subcutaneous (SC) Use

Tocilizumab (Actemra) SC injection may be considered medically necessary when an individual meets the criteria for ANY ONE of the following indications:

• Giant Cell Arteritis (GCA):
  • The individual is 18 years of age and older for the treatment of GCA; and
  • Treatment with at least one (1) systemic corticosteroid (e.g., prednisone) was ineffective or not tolerated, or all corticosteroids are contraindicated; or
• Juvenile Idiopathic Arthritis, Polyarticular (PJIA):
  • The individual is two (2) years of age and older with PJIA; and
  • ONE of the following criteria is met:
    • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
    • The individual requires initial biologic therapy due to involvement of high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, and/or those judged by their physician to be at high risk of disabling joint damage; and
• Systemic Juvenile Idiopathic Arthritis (SJIA):
  • The individual is two (2) years of age and older with active SJIA; or

• Rheumatoid Arthritis (RA):
  • The individual is 18 years of age and older with moderately to severely active RA; and
  • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
• Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)
  • The individual is 18 years of age or older with SSc-ILD; and
  • Tocilizumab (Actemra) is being prescribed by or in consultation with a pulmonologist or rheumatologist; and
  • The individual has documentation of a high-resolution chest computed tomography (HRCT) scan demonstrating greater than or equal to 10% pulmonary fibrosis; and
  • The individual has a baseline forced vital capacity (FVC) of at least 40% and a percent predicted diffusing capacity of the lungs of carbon monoxide (DLCO) of at least 30%; and
  • The individual is a non-smoker or is currently engaged in smoking cessation.

Reauthorization Criteria

Continuation of therapy with tocilizumab (Actemra) for may be considered medically necessary when the following criteria are met:

• The individual has one of the above diagnoses; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of tocilizumab (Actemra SC) not meeting the criteria as indicated in this policy is considered not medically necessary.

Tocilizumab-bavi (Tofidence)

Tocilizumab-bavi (Tofidence) may be considered medically necessary when an individual meets the criteria for ANY ONE of the following:

• Juvenile Idiopathic Arthritis, Polyarticular (PJIA):
  • The individual is two (2) years of age and older with PJIA; and
  • ONE of the following criteria is met:
    • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
    • The individual requires initial biologic therapy due to involvement or high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, and/or those judges by their physician to be at high risk of disabling joint damage; or
• Systemic Juvenile Ipiopathic Arthritus (Sjia):
  • The individual is two (2) years of age and older with active SJIA; and
  • Treatment with at least one (1) non-biologic DMARD (e.g. methotrexate, leflunomide, sulfasalazine) was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
• Rheumatoid Arthritis (RA):
  • The individual is 18 years of age and older with moderately to severaly active RA; and
  • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerate, or all non-biologic DMARDs are contraindicated.

Reauthorization Criteria

Continuation of therapy with tocilizumab-bavi (Tofidence) for may be considered medically necessary when the following criteria are met:

• The individual has one of the above diagnoses; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response therapy; and
• Reauthorization valid for 12 months.

The use of tocilizumab-bavi (tofidence) not meeting the criteria as indicated in this policy is considered not medically necessary. 

Tocilizumab-aazg (Tyenne)

Tocilizumab-aazg (Tyenne) may be considered medically necessary when an individual meets the criteria for ANY ONE of the following:

• Giant Cell Arthritis (GCA) 
  • The individual is 18 years of age and older for the treatment of GCA; and
  • Treatment with at least one (1) systemic corticosteroid (e.g., prednisone) was ineffective or not tolerated, or all corticosteroids are contraindicated; or
• Juvenile Idiopathic Arthritis, Polyarticular (PJIA):
  • The individual is two (2) years of age and older with PJIA; and
  • ONE of the following criteria is met:
    • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
    • The individual requires initial biologic therapy due to involvement of high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, and/or those judged by their physician to be at high risk of disabling joint damage; or
• Systemic Juvenile Idiopathic Arthritis (SJIA):
  • The individual is two (2) years of age and older with active SJIA; and
  • Treatment with at least one (1) non-biologic DMARD (e.g. methotrexate, leflunomide, sulfasalazine) was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated; or
• Rheumatoid Arthritis (RA):
  • The individual is 18 years of age and older with moderately to severely active RA; and
  • Treatment with at least one (1) non-biologic DMARD was ineffective or not tolerated, or all non-biologic DMARDs are contraindicated.

Reauthorization Criteria

Continuation of therapy with tocilizumab-aazg (Tyenne) for may be considered medically necessary when the following criteria are met:

• The individual has one of the above diagnoses; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of tocilizumab-aazg (Tyenne) not meeting the criteria as indicated in this policy is considered not medically necessary.

Tocilizumab (Actemra) and tocilizumab-bavi (Tofidence) may be considered medically necessary for individuals 18 years of age and older when applicable clinical criteria for individual medication policies are met and when administered in a physician’s office not affiliated with a hospital, specialized infusion centers not affiliated with a hospital or in the home. 

Outpatient facility (Outpatient Hospital IV Infusion Department or Hospital-based Outpatient Clinical Level of Care) administration may be considered medically necessary if ANY of the following criteria are present to indicate the member is medically unstable for infusions in other than an outpatient facility setting:

• Member’s home is considered unsuitable for care by the home infusion provider; or
• Individual’s medical status requires enhanced monitoring beyond that which would routinely be needed for infusion therapy; or
• Previous severe adverse reaction (including but not limited to anaphylaxis, seizure, thromboembolism, myocardial infarction, renal failure) during or following administration of prescribed medication despite standard pre-medication; or
• Individual is receiving other medications that require close monitoring with a higher level of care (e.g., cytotoxic chemotherapy or blood products); or
• Individual is at high risk for complications due to medication administration (e.g., at risk for post-transplant complications, increased risk of infusion reactions due to presence of circulating antibodies, unstable vascular access, cardiopulmonary condition at risk for severe adverse reactions, unstable renal function with inability to safely tolerate IV volume loads, etc.); or 
• Individual is initiating therapy or re-initiating therapy after a period of at least 6 months with no therapy; or
• Physically and/or cognitively impaired AND a home caregiver is not available to comply with the required treatment regimen and schedule.

Home health services may be considered medically necessary when utilized for the administration of home infusion therapy and when provided by licensed eligible provider. Each case will be addressed on an individual basis.

The medications identified in this policy will be considered not medically necessary if administered in an unapproved hospital outpatient setting when an approved site of care is a viable option for treatment.

NOTE: If an individual has already had a trial of at least one biologic agent, they are not required to “step back” and try a non-biologic agent.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Evidence-based guidelines support the administration of injectable medications in alternative sites of care such as the non-hospital physician’s office, non-hospital infusion center or in the home.  Administration of the injectable medications subject to this policy at alternate sites of care is based upon the professional judgment of the provider, and takes into account the clinical appropriateness for each individual member. Requests for administration of any dose of the drugs listed in this policy received from a hospital-based facility, physician’s office or specialized infusion center will be assessed for meeting the policy exception criteria based on the clinical documentation provided by the requesting practitioner.