Infliximab (Remicade®) is a murine-human chimeric monoclonal antibody, which binds to and neutralizes the effects of tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine.

Infliximab-axxq (Avsola^TM), infliximab-dyyb (Inflectra®) and infliximab-abda (Renflexis®) are biosimilar murine-human chimeric monoclonal antibodies to infliximab (Remicade). Both infliximab (Remicade) and its biosimilars, infliximab-axxq (Avsola), inflixmab-dyyb (Inflectra) and infliximab-abda (Renflexis) have the same mechanism of action. 

Preferred Products

Infliximab-axxq (Avsola) and Inflixmab-dyyb (Inflectra) are the preferred infliximab products for all individuals and all indications. The initial authorization will be valid for 12 months and the reauthorization will be valid for 12 months.

Non-Preferred Intravenous Injectable Product(s)

In order for a request for a non-preferred product infliximab (Remicade) or infliximab-abda (Renflexis)] to be approved the individual must have had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to both of the preferred products. The initial authorization will be valid for 12 months and the reauthorization will be valid for 12 months.

Adequate therapeutic trial is defined as six (6) months from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

Infliximab (Remicade) or an infliximab biosimilar (Avsola, Inflectra or Renflexis), may be considered medically necessary for an initial authorization period of 12 months when an individual meets the criteria for ANY ONE of the following indications:

• Ankylosing Spondylitis (AS)
  • The individual is 18 years of age or older with AS; and
  • Treatment with at least one (1) nonsteroidal anti-inflammatory drug (NSAID) was ineffective or not tolerated, or all NSAIDs are contraindicated; or

• Crohn's Disease (CD)
  • The individual is six (6) years of age or older with moderate to severe CD (including fistulizing CD); or

• Graft-Versus-Host Disease (GVHD)
  • Individual is 18 years of age or older and has a diagnosis of steroid refractory acute GVHD; or
• Immune Checkpoint Inhibitor-Related Toxicities:
  • The individual is 18 years of age or older; and
  • Individual has recently received checkpoint inhibitor therapy (e.g. pembrolizumab, nivolumab); and
  • Individual has a diagnosis one (1) of the following
    • Severe or life-threatening immunotherapy-related myocarditis, pericarditis, arrhythmias, impaired ventricular function or conduction abnormalities; or
    • Moderate to severe imunnotherapy-related diarrhea or colitis; or
    • Severe immunotherapy-related pneumonitis; or
    • Severe or life-threatening immunotherapy-related acute renal failure; or
    • Severe immunotherapy-related uveitis; or
    • Severe immunotherapy-related arthritis; or
    • Moderate, severe, or life-threatening immunotherapy-related, steroid-refractory myalgias or myositis; and
  • Individual has not had improvement in symptoms despite appropriate systemic corticosteroid therapy of adequate dose and duration for the diagnosis; or

• Juvenile Rheumatoid Arthritis (JRA)/Juvenile Idiopathic Arthritis (JIA)
  • The treatment of individuals who have had an inadequate response to one (1) or more disease-modifying antirheumatic drugs (DMARDs); or

• Plaque Psoriasis (PsO)
  • The individual is 18 years of age or older with chronic, severe (i.e., extensive and/or disabling) PsO; and
  • Individual's PsO has been present for more than six (6) months with a minimum body surface involvement of 10% (In individuals with severe disease, localized psoriasis in sensitive areas such as palmar, plantar, and genitalia would meet the 10% body surface involvement definition); and
  • Individual has failed to adequately respond to standard systemic agents (e.g., methotrexate, cyclosporine); or
  • Individual has failed to adequately respond to standard phototherapy (e.g., PUVA, UVB); or

• Psoriatic Arthritis (PsA)
  • Treatment of individuals 18 years of age or older with PsA; or

• Rheumatoid arthritis (RA)
  • The individual is 18 years of age or older with moderate to severe RA; and
  • Used in combination with methotrexate in individuals who have had an inadequate response to methotrexate, as standard therapy; or

• Ulcerative Colitis (UC)
  • The individual is six (6) years of age or older with moderate to severe UC; or
• Sarcoidosis
  • The individual is 18 years of age or older with a diagnosis of sarcoidosis; and
  • Individual has experienced treatment failure, intolerance or has a contraindication to conventional therapies including corticosteroids and immunosuppressants (e.g., methotrexate, cyclophosphamide, azathioprine); and
  • Individual is not receiving infliximab in combination with a disease-modifying antirheumatic drug (DMARD) or a janus kinase inhibitor; or

• Non-infectious Uveitis 
  • The individual has non-infectious uveitis; and
  • Individual has chronic, recurrent, treatment-refractory or vision-threatening disease; and
  • Individual has failed to respond to, is intolerant of, or has a medical contraindication to conventional therapy (such as corticosteroids or immunosuppressive drugs [for example, azathioprine, cyclosporine, or methotrexate]).

The use of infliximab or an infliximab biosimilar for the treatment of GVHD or immune checkpoint inhibitor-related toxicities exceeding four (4) treatment courses per six (6) month period may be considered experimental/investigational, and therefore, non-covered.

The use of infliximab (Remicade), an infliximab biosimilar (Avsola, Inflectra or Renflexis), for any other indication is considered not medically necessary.

Reauthorization Criteria for Infliximab (Remicade) or Infliximab Biosimilar (Avsola, Inflectra or Renflexis)

• Continuation of therapy with infliximab (Remicade) or infliximab biosimilar (Avsola, Inflectra or Renflexis) IV may be considered medically necessary when the following criteria is met:
  • The individual has one of the above diagnoses; and
  • For a non-preferred product [infliximab (Remicade) or infliximab-abda (Renflexis)] the individual has had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to both of the preferred products; and
  • Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
  • Reauthorization valid for 12 months.

The use of infliximab (Remicade), an infliximab biosimilar (Avsola, Inflectra or Renflexis), for any other indication is considered not medically necessary. 

NOTE: Infliximab is not FDA approved for the treatment of rheumatoid arthritis without methotrexate. However, individual consideration will be given to patients who are unable to tolerate methotrexate (e.g., abnormal liver function, depressed hemopoietic function, etc.).

Infliximab (Remicade) or an infliximab biosimilar (Avsola, Inflectra and Renflexis) 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: 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.

Infliximab (Remicade) and infliximab biosimilars are typically an outpatient procedures which are only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.