Coverage Policy Manual
Policy #: 2020022
Category: Pharmacy
Initiated: September 2020
Last Review: May 2024
  Tocilizumab (e.g., Actemra) and Biosimilars
Description:
Tocilizumab is a recombinant humanized  anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass with a typical H2L2 polypeptide structure. Each light chain and heavy chain consists of 214 and 448 amino acids, respectively. The four polypeptide chains are linked intra-and inter-molecularly by disulfide bonds. Tocilizumab has a molecular weight of approximately 148 kDa. The antibody is produced in mammalian (Chinese hamster ovary) cells.
 
Tocilizumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R) and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.
 
Regulatory Status
 
Tocilizumab (e.g., Actemra) is approved by the U.S. Food and Drug Administration (FDA) for the following indications:
1. Moderately to severely active Rheumatoid Arthritis (RA) in individuals who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs.
2. Giant Cell Arteritis (GCA)
3. Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)
4. Polyarticular Juvenile Idiopathic Arthritis (PJIA)
5. Systemic Juvenile Idiopathic Arthritis (SJIA)
6. Chimeric antigen receptor (CAR) T cell-induced severe or life-threatening Cytokine Release Syndrome
 
On March 5, 2024, the U.S. Food and Drug Administration approved tocilizumab-aazg (e.g., Tyenne) for intravenous use as biosimilar to tocilizumab (e.g., Actemra) for the following indications:
1. Rheumatoid Arthritis (RA);
2. Giant Cell Arteritis (GCA);
3. Polyarticular Juvenile Idiopathic Arthritis (PJIA) in individuals 2 years of age and older;
4. Systemic Juvenile Idiopathic Arthritis (SJIA) in individuals 2 years of age and older.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
The use of Tocilizumab subcutaneous injection is not covered under the medical benefit. Please see pharmacy benefit.
 
The use of Tocilizumab intravenous infusion is covered under the medical benefit.
 
This policy does not apply to the use of the tocilizumab (e.g., Actemra) in the inpatient or emergency room settings but the use of tocilizumab in these sites must be for an FDA approved indication.
 
Effective April 01, 2022 Prior Approval is required for tocilizumab.
 
The Step Therapy Medication Act is applicable to fully-insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups).  Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective January 29, 2025
  
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Tocilizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met based on diagnosis:
 
Note: Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
RHEUMATOID ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is 18 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe rheumatoid arthritis (RA) supported by the submitted medical records; AND
    3. Individual has an active disease with inadequate response (trial of greater than or equal to 3 months) to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
    4. Individual has an active disease with documented intolerance or contraindication to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
    5. Individual has previously received a biologic (e.g., etanercept, infliximab, adalimumab, certolizumab, tocilizumab, sarilumab, golimumab, abatacept, anakinra, rituximab) or synthetic DMARD (tofacitinib, baricitinib, upadacitinib) indicated for rheumatoid arthritis (Fraenkel, 2021); AND
    6. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    7. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
    1. Individual has met criteria for initial approval; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    4. Must be dosed in accordance with the FDA label.
 
GIANT CELL ARTERITIS
 
INTIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is 18 years of age or older; AND
    2. Individual has a diagnosis of Giant Cell Arteritis (GCA); AND
    3. Tocilizumab is used in combination with a tapering course of corticosteroids (e.g., prednisone); OR
    4. Tocilizumab is used as a single agent following discontinuation of corticosteroids; AND
    5. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
    1. Individual has met initial criteria for a diagnosis of GCA; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    4. Must be dosed in accordance with the FDA label.
 
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is 2 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis (pJIA); AND
    3. Individual an active disease with documented inadequate response (trial of ≥3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
    4. Individual has an active disease with intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
    5. Individual has previously received a biologic (e.g., golimumab, abatacept, tocilizumab) or targeted synthetic drug (e.g., tofacitinib) indicated for pJIA (Ringold, 2019); OR
    6. Individual has disease involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage as assessed by rheumatologist/immunologist (Kimura, 2021); AND
    7. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    8. Must be dosed in accordance with FDA label.
 
CONTINUED APPROVAL for up to 1 year:
    1. Individual has met initial criteria for a diagnosis of pJIA; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND      
    4. Must be dosed in accordance with the FDA label.
 
SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is 2 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe juvenile idiopathic arthritis (JIA); AND
    3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
    4. Individual has an active disease with documented intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
    5. Individual has previously received a biologic (e.g., adalimumab, etanercept, abatacept) or targeted synthetic drug (e.g., tofacitinib) indicated for treatment of JIA (Ringold, 2019); OR
    6. Individual is at high risk for disabling joint disease as assessed by a provider who specializes in juvenile idiopathic arthritis (Onel, 2022); AND
    7. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    8. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
1. Individual has met initial criteria for a diagnosis of JIA; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
4. Must be dosed in accordance with the FDA label.
 
CYTOKINE RELEASE SYNDROME
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
CONTINUED APPROVAL for up to 1 year:
    1. Individual meets criteria for initial approval based on indication; AND  
    2. Individual has experienced a positive clinical response to tocilizumab; AND
    3. Individual is not taking tocilizumab concomitantly with any other biologic DMARD (e.g., adalimumab, etanercept, golimumab, certolizumab, abatacept) or targeted synthetic DMARD (e.g., apremilast or tofacitinib); AND
    4. Must be dosed in accordance with the FDA label.
 
Policy Guidelines
 
Prescriber is responsible for verification that Individual does not have latent tuberculosis or serious active infection before starting the treatment.
 
Examples of Contraindications to Methotrexate:
    1. Alcoholism, alcoholic liver disease or other chronic liver disease;
    2. Breastfeeding;
    3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia);
    4. Elevated liver transaminases;
    5. History of intolerance or adverse event;
    6. Hypersensitivity;
    7. Interstitial pneumonitis or clinically significant pulmonary fibrosis;
    8. Myelodysplasia;
    9. Pregnancy or planning pregnancy (male or female);
    10. Renal impairment;
    11. Significant drug interaction;
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended intravenous dose of Tocilizumab is based on indication:
 
Rheumatoid Arthritis- 4 mg/kg every four weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response. Doses exceeding 800 mg per infusion are not recommended.
 
Giant Cell Arteritis- 6 mg/kg every 4 weeks in combination with a tapering course of glucocorticoids, Tocilizumab can be used alone following discontinuation of glucocorticoids.
 
Polyarticular Juvenile Idiopathic Arthritis- 10 mg/kg every four weeks in patients less than 30 kg and 8 mg/kg every four weeks in individuals at or above 30 kg
 
Systemic Juvenile Idiopathic Arthritis- 12 mg/kg every two weeks in patients less than 30 kg and 8 mg/kg every two weeks in individuals at or above 30 kg
 
Cytokine Release Syndrome- 12 mg/kg in individuals less than 30 kg and 8 mg/kg in individuals at or above 30 kg alone or in combination with corticosteroids. Up to three additional doses of Tocilizumab may be administered but the interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended.
 
Tocilizumab intravenous infusion is available in 80 mg, 200 mg, or 400 mg single-dose vials.
 
Tocilizumab subcutaneous injection is available in a 162 mg prefilled syringe or a 162 mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, Tocilizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective May 15, 2024 to January 28, 2025
  
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Tocilizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met based on diagnosis:
 
Note: Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
RHEUMATOID ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 18 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe rheumatoid arthritis (RA) supported by the submitted medical records; AND
    3. Individual has an active disease with inadequate response (trial of greater than or equal to 3 months) to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
    4. Individual has an active disease with documented intolerance or contraindication to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
    5. Individual has previously received a biologic (e.g., etanercept, infliximab, adalimumab, certolizumab, tocilizumab, sarilumab, golimumab, abatacept, anakinra, rituximab) or synthetic DMARD (tofacitinib, baricitinib, upadacitinib) indicated for rheumatoid arthritis (Fraenkel, 2021); AND
    6. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    7. Individual does not have latent tuberculosis or serious active infection; AND
    8. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
    1. Individual has met criteria for initial approval; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    4. Must be dosed in accordance with the FDA label.
 
GIANT CELL ARTERITIS
 
INTIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 18 years of age or older; AND
    2. Individual has a diagnosis of Giant Cell Arteritis (GCA); AND
    3. Tocilizumab is used in combination with a tapering course of corticosteroids (e.g., prednisone); OR
    4. Tocilizumab is used as a single agent following discontinuation of corticosteroids; AND
    5. Individual does not have latent tuberculosis or serious active infection; AND
    6. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
    1. Individual has met initial criteria for a diagnosis of GCA; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    4. Must be dosed in accordance with the FDA label.
 
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 2 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis (pJIA); AND
    3. Individual an active disease with documented inadequate response (trial of ≥3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
    4. Individual has an active disease with intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
    5. Individual has previously received a biologic (e.g., golimumab, abatacept, tocilizumab) or targeted synthetic drug (e.g., tofacitinib) indicated for pJIA (Ringold, 2019); OR
    6. Individual has disease involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage as assessed by rheumatologist/immunologist (Kimura, 2021); AND
    7. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    8. Individual does not have latent tuberculosis or serious active infection; AND
    9. Must be dosed in accordance with FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
    1. Individual has met initial criteria for a diagnosis of pJIA; AND
    2. Individual has experienced a documented positive clinical response; AND
    3. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND      
    4. Must be dosed in accordance with the FDA label.
 
SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 2 years of age or older; AND
    2. Individual has a diagnosis of moderate to severe juvenile idiopathic arthritis (JIA); AND
    3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
    4. Individual has an active disease with documented intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
    5. Individual has previously received a biologic (e.g., adalimumab, etanercept, abatacept) or targeted synthetic drug (e.g., tofacitinib) indicated for treatment of JIA (Ringold, 2019); OR
    6. Individual is at high risk for disabling joint disease as assessed by a provider who specializes in juvenile idiopathic arthritis (Onel, 2022); AND
    7. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
    8. Individual does not have latent tuberculosis or serious active infection; AND
    9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
 
1. Individual has met initial criteria for a diagnosis of JIA; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
4. Must be dosed in accordance with the FDA label.
 
CYTOKINE RELEASE SYNDROME
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
CONTINUED APPROVAL for up to 1 year:
 
    1. Individual meets criteria for initial approval based on indication; AND  
    2. Individual has experienced a positive clinical response to tocilizumab; AND
    3. Individual is not taking tocilizumab concomitantly with any other biologic DMARD (e.g., adalimumab, etanercept, golimumab, certolizumab, abatacept) or targeted synthetic DMARD (e.g., apremilast or tofacitinib); AND
    4. Must be dosed in accordance with the FDA label.
 
Policy Guidelines
 
Examples of Contraindications to Methotrexate:
    1. Alcoholism, alcoholic liver disease or other chronic liver disease;
    2. Breastfeeding;
    3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia);
    4. Elevated liver transaminases;
    5. History of intolerance or adverse event;
    6. Hypersensitivity;
    7. Interstitial pneumonitis or clinically significant pulmonary fibrosis;
    8. Myelodysplasia;
    9. Pregnancy or planning pregnancy (male or female);
    10. Renal impairment;
    11. Significant drug interaction;
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended intravenous dose of Tocilizumab is based on indication:
 
Rheumatoid Arthritis- 4 mg/kg every four weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response. Doses exceeding 800 mg per infusion are not recommended.
 
Giant Cell Arteritis- 6 mg/kg every 4 weeks in combination with a tapering course of glucocorticoids, Tocilizumab can be used alone following discontinuation of glucocorticoids.
 
Polyarticular Juvenile Idiopathic Arthritis- 10 mg/kg every four weeks in patients less than 30 kg and 8 mg/kg every four weeks in individuals at or above 30 kg
 
Systemic Juvenile Idiopathic Arthritis- 12 mg/kg every two weeks in patients less than 30 kg and 8 mg/kg every two weeks in individuals at or above 30 kg
 
Cytokine Release Syndrome- 12 mg/kg in individuals less than 30 kg and 8 mg/kg in individuals at or above 30 kg alone or in combination with corticosteroids. Up to three additional doses of Tocilizumab may be administered but the interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended.
 
Tocilizumab intravenous infusion is available in 80 mg, 200 mg, or 400 mg single-dose vials.
 
Tocilizumab subcutaneous injection is available in a 162 mg prefilled syringe or a 162 mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, Tocilizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective January 2024 to may 14, 2024
  
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Tocilizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met based on diagnosis:
 
Note: Giant Cell Arteritis and Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
RHEUMATOID ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual is greater than or equal to 18 years of age; AND
2. Individual has a diagnosis of moderate to severe rheumatoid arthritis (RA) supported by the submitted medical records; AND
3. Individual has an active disease with inadequate response (trial of greater than or equal to 3 months) to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
4. Individual has an active disease with documented intolerance or contraindication to at least one conventional synthetic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine) (Fraenkel, 2021); OR
5.Individual has previously received a biologic (e.g., etanercept, infliximab, adalimumab, certolizumab, tocilizumab, sarilumab, golimumab, abatacept, anakinra, rituximab) or synthetic DMARD (tofacitinib, baricitinib, upadacitinib) indicated for rheumatoid arthritis (Fraenkel, 2021); AND
6. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
7. Individual does not have latent tuberculosis or serious active infection; AND
8. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
1. Individual has met criteria for initial approval; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with other biologic intended for treatment of rheumatoid arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
4. Must be dosed in accordance with the FDA label.
 
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
1. Individual is greater than or equal to 2 years of age; AND
2. Individual has a diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis (pJIA); AND
3. Individual an active disease with documented inadequate response (trial of ≥3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
4. Individual has an active disease with intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARDs (e.g., methotrexate, sulfasalazine) indicated for pJIA (Ringold, 2019); OR
5. Individual has previously received a biologic (e.g., golimumab, abatacept, tocilizumab) or targeted synthetic drug (e.g., tofacitinib) indicated for pJIA (Ringold, 2019); OR
6. Individual has disease involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage as assessed by rheumatologist/immunologist (Kimura, 2021); AND
7. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Individual does not have latent tuberculosis or serious active infection; AND
9 Must be dosed in accordance with FDA label.
 
CONTINUED APPROVAL for up to 1 year:
1. Individual has met initial criteria for a diagnosis of pJIA; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with other biologic intended for treatment of polyarticular juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND     
4. Must be dosed in accordance with the FDA label.
 
SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
1. Individual is greater than or equal to 2 years of age; AND
2. Individual has a diagnosis of moderate to severe juvenile idiopathic arthritis (JIA); AND
3. Individual has an active disease with documented inadequate response (trial of greater than or equal to 3 months) to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
4. Individual has an active disease with documented intolerance or contraindication to scheduled NSAIDs (e.g., indomethacin, naproxen, celecoxib) or synthetic DMARD (e.g., methotrexate) indicated for treatment of JIA (Ringold, 2019); OR
5. Individual has previously received a biologic (e.g., adalimumab, etanercept, abatacept) or targeted synthetic drug (e.g., tofacitinib) indicated for treatment of JIA (Ringold, 2019); OR
6. Individual is at high risk for disabling joint disease as assessed by a provider who specializes in juvenile idiopathic arthritis (Onel, 2022); AND
7. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
8. Individual does not have latent tuberculosis or serious active infection; AND
9. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year:
1. Individual has met initial criteria for a diagnosis of JIA; AND
2. Individual has experienced a documented positive clinical response; AND
3. Individual is not using the medication in combination with other biologic intended for treatment of juvenile idiopathic arthritis, including but not limited to: TNF inhibitor, IL-36 inhibitor, PDE4 inhibitor, any other IL inhibitor, or Janus kinase inhibitor; AND
4. Must be dosed in accordance with the FDA label.
 
CYTOKINE RELEASE SYNDROME
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
CONTINUED APPROVAL for up to 1 year:
    1. Individual meets criteria for initial approval based on indication; AND  
2. Individual has experienced a positive clinical response to tocilizumab; AND
3. Individual is not taking tocilizumab concomitantly with any other biologic DMARD (e.g., adalimumab, etanercept, golimumab, certoliumab, abatacept) or targeted synthetic DMARD (e.g., apremilast or tofacitinib); AND
4. Must be dosed in accordance with the FDA label; AND
 
Policy Guidelines
Examples of Contraindications to Methotrexate:
1. Alcoholism, alcoholic liver disease or other chronic liver disease;
2. Breastfeeding;
3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia);
4. Elevated liver transaminases;
5. History of intolerance or adverse event;
6. Hypersensitivity;
7. Interstitial pneumonitis or clinically significant pulmonary fibrosis;
8. Myelodysplasia;
9. Pregnancy or planning pregnancy (male or female);
10. Renal impairment;
11. Significant drug interaction;
 
 
 
Effective September 2023 - December 2023
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Tocilizumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
Rheumatoid Arthritis (Fraenkel, et.al., 2021)
Individual is 18 years of age or older and has a diagnosis of moderate to severely active rheumatoid arthritis AND
    1. Individual has previously received a biologic DMARD (i.e., abatacept, rituximab, TNF inhibitors) or a targeted synthetic (ts) DMARD (i.e., tofacitinib) indicated for moderately to severely active rheumatoid arthritis; AND
    2. Individual has experienced an inadequate response to at least a 3-month trial of a conventional synthetic (CS) DMARD (i.e., hydroxychloroquine, leflunomide, methotrexate, or sulfalazine); OR
    3. Individual has an intolerance or contraindication to conventional (cs) DMARDs; AND
    4. Will not be used:
a. In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies;  OR
b. When individual has tuberculosis, other active serious infections, or a history of recurrent infections; OR
c. When individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab.
 
Polyarticular Juvenile Idiopathic Arthritis (Ringold, et.al., 2019)
Individual is 2 years of age or older and has a diagnosis of polyarticular juvenile idiopathic arthritis; AND
    1. Individual has previously received a biologic for polyarticular juvenile idiopathic arthritis; OR
    2. Individual has had an inadequate response to conventional DMARD (i.e., methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine); OR
    3. Individual has involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage that warrants a biologic as first line therapy; AND
    4. Will not be used:
a. In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies; OR
b. When individual has tuberculosis, other active serious infections, or a history of recurrent infections; OR
c. When individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab.
 
Systemic Juvenile Idiopathic Arthritis (Ringold, et.al., 2013)
Individual is 2 years of age or older and has a diagnosis of systemic juvenile idiopathic arthritis AND
    1. Individual has previously received a biologic for systemic juvenile idiopathic arthritis; OR
    2. Individual has had an inadequate response to at least a three-month trial of NSAIDs; OR
    3. Individual has had an inadequate response to at least a three-month trial of methotrexate or leflunomide; AND
    4. Will not be used:
a. In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies; OR
b. When individual has tuberculosis, other active serious infections, or a history of recurrent infections; OR  
c. When individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab.  
 
Cytokine Release Syndrome
Individual is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
Note: Giant Cell Arteritis and Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
CONTINUATION OF THERAPY for 12 months
 
1. Individual meets criteria for initial approval based on indication; AND
2. Individual has experienced a positive clinical response to tocilizumab; AND
3. Individual is not taking tocilizumab concomitantly with any other biologic DMARD (e.g., adalimumab, etanercept, golimumab, certoliumab, abatacept) or targeted synthetic DMARD (e.g., apremilast or tofacitinib); AND
4. Must be dosed in accordance with the FDA label; AND
5. Will not be used:
a. In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies; OR
b. When individual has tuberculosis, other active serious infections, or a history of recurrent infections; OR
c. When individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab.
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended intravenous dose of Tocilizumab is based on indication:
 
Rheumatoid Arthritis- 4 mg/kg every four weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response. Doses exceeding 800 mg per infusion are not recommended.
 
Polyarticular Juvenile Idiopathic Arthritis- 10 mg/kg every four weeks in patients less than 30 kg and 8 mg/kg every four weeks in individuals at or above 30 kg
 
Systemic Juvenile Idiopathic Arthritis- 12 mg/kg every two weeks in patients less than 30 kg and 8 mg/kg every two weeks in individuals at or above 30 kg
 
Cytokine Release Syndrome- 12 mg/kg in individuals less than 30 kg and 8 mg/kg in individuals at or above 30 kg alone or in combination with corticosteroids. Up to three additional doses of Tocilizumab may be administered but the interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended.
 
Tocilizumab intravenous infusion is available in 80 mg, 200 mg, or 400 mg single-dose vials.
 
Tocilizumab subcutaneous injection is available in a 162 mg prefilled syringe or a 162 mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, Tocilizumab, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 1, 2022 to August 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Tocilizumab meets primary coverage criteria when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
Rheumatoid Arthritis (Fraenkel, et.a., 2021)
Member is 18 years of age or older and has a diagnosis of moderate to severely active rheumatoid arthritis AND
    1. Member has previously received a biologic DMARD (i.e. abatacept, rituximab, TNF inhibitors) or a targeted synthetic (ts) DMARD (tofacitinib) indicated for moderately to severely active rheumatoid arthritis AND
    2. Member has experienced an inadequate response to at least a 3-month trial of a conventional synthetic (CS) DMARD (i.e. hydroxychloroquine, leflunomide, methotrexate, or sulfalazine) OR
    3. Member has an intolerance or contraindication to conventional (cs) DMARDs
 
Polyarticular Juvenile Idiopathic Arthritis (Ringold, et.al., 2019)
Member is 2 years of age or older and has a diagnosis of polyarticular juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for polyarticular juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to conventional DMARD (methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine) OR
    3. Member has involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage that warrants a biologic as first line therapy
 
Systemic Juvenile Idiopathic Arthritis (Ringold, et.al., 2013)
Member is 2 years of age or older and has a diagnosis of systemic juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for systemic juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to at least a three-month trial of NSAIDs OR
    3. Member has had an inadequate response to at least a three-month trial of methotrexate or leflunomide
 
Cytokine Release Syndrome
Member is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
CONTINUATION OF THERAPY for 12 months:
1. Member meets criteria for initial approval based on indication.
2. Member has experienced a positive clinical response to tocilizumab.
3. Member is not taking tocilizumab concomitantly with any other bilogic DMARD (e.g., adalimumab, etanercept, golimumab, certoliumab, abatacept) or targeted synthetic DMARD (e.g., apremilast or tofacitinib).
4. Dosed in accordance with FDA labeling.
 
Giant Cell Arteritis and Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
Dosage and Administration (FDA, 2021)
 
The recommended intravenous dose of Tocilizumab is based on indication:
 
Rheumatoid Arthritis- 4mg/kg every four weeks followed by an increase to 8mg/kg every 4 weeks based on clinical response. Doses exceeding 800mg per infusion are not recommended.
 
Polyarticular Juvenile Idiopathic Arthritis- 10mg/kg every four weeks in patients less than 30kg and 8mg/kg every four weeks in patients at or above 30kg
 
Systemic Juvenile Idiopathic Arthritis- 12mg/kg every two weeks in patients less than 30kg and 8mg/kg every two weeks in patients at or above 30kg
 
Cytokine Release Syndrome- 12mg/kg in patients less than 30kg and 8mg/kg in patients at or above 30kg alone or in combination with corticosteroids. Up to three additional doses of Tocilizumab may be administered but the interval between consecutive doses should be at least 8 hours. Doses exceeding 800mg per infusion are not recommended.
 
Tocilizumab intravenous infusion is available in 80mg, 200mg, or 400mg single-dose vials.
 
Tocilizumab subcutaneous injection is available in a 162mg prefilled syringe or a 162mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab does not meet member benefit certificate primary coverage criteria for any of the following (FDA, 2021):
  • Any other indication not included above OR
  • In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies OR
  • Tuberculosis, other active serious infections, or a history of recurrent infections OR  
  • Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab (ActemraTM)
 
For members with contracts without primary coverage criteria, the use of Tocilizumab in any other condition than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
EffectiveSeptember, 2021 to March 31, 2022
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Tocilizumab (ActemraTM) meets primary coverage criteria when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
Rheumatoid Arthritis (Fraenkel, et.a., 2021)
Member is 18 years of age or older and has a diagnosis of moderate to severely active rheumatoid arthritis AND
    1. Member has previously received a biologic DMARD (i.e. abatacept, rituximab, TNF inhibitors) or a targeted synthetic (ts) DMARD (tofacitinib) indicated for moderately to severely active rheumatoid arthritis AND
    2. Member has experienced an inadequate response to at least a 3-month trial of a conventional synthetic (CS) DMARD (i.e. hydroxychloroquine, leflunomide, methotrexate, or sulfalazine) OR
    3. Member has an intolerance or contraindication to conventional (cs) DMARDs
 
Polyarticular Juvenile Idiopathic Arthritis (Ringold, et.al., 2019)
Member is 2 years of age or older and has a diagnosis of polyarticular juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for polyarticular juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to conventional DMARD (methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine) OR
    3. Member has involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage that warrants a biologic as first line therapy
 
Systemic Juvenile Idiopathic Arthritis (Ringold, et.al., 2013)
Member is 2 years of age or older and has a diagnosis of systemic juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for systemic juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to at least a three-month trial of NSAIDs OR
    3. Member has had an inadequate response to at least a three-month trial of methotrexate or leflunomide
 
Cytokine Release Syndrome
Member is at least 2 years of age with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (FDA, 2021)
 
Giant Cell Arteritis and Systemic Sclerosis-Associated Interstitial Lung Disease-Tocilizumab is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
Dosage and Administration (FDA, 2021)
 
The recommended intravenous dose of Tocilizumab (ActemraTM) is based on indication:
 
Rheumatoid Arthritis- 4mg/kg every four weeks followed by an increase to 8mg/kg every 4 weeks based on clinical response. Doses exceeding 800mg per infusion are not recommended.
 
Polyarticular Juvenile Idiopathic Arthritis- 10mg/kg every four weeks in patients less than 30kg and 8mg/kg every four weeks in patients at or above 30kg
 
Systemic Juvenile Idiopathic Arthritis- 12mg/kg every two weeks in patients less than 30kg and 8mg/kg every two weeks in patients at or above 30kg
 
Cytokine Release Syndrome- 12mg/kg in patients less than 30kg and 8mg/kg in patients at or above 30kg alone or in combination with corticosteroids. Up to three additional doses of Tocilizumab (ActemraTM) may be administered but the interval between consecutive doses should be at least 8 hours. Doses exceeding 800mg per infusion are not recommended.
 
Tocilizumab (ActemraTM) intravenous infusion is available in 80mg, 200mg, or 400mg single-dose vials.
 
Tocilizumab (ActemraTM) subcutaneous injection is available in a 162mg prefilled syringe or a 162mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab (ActemraTM) does not meet member benefit certificate primary coverage criteria for any of the following (FDA, 2021):
    • Any other indication not included above OR
    • In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies OR
    • Tuberculosis, other active serious infections, or a history of recurrent infections OR  
    • Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab (ActemraTM)
 
For members with contracts without primary coverage criteria, the use of Tocilizumab (ActemraTM) in any other condition than listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
EffectiveSeptember, 2020 to August, 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Tocilizumab (ActemraTM) meets primary coverage criteria when dosed in accordance with FDA approved labeling AND when the following criteria are met based on diagnosis:
 
Rheumatoid Arthritis
Member is 18 years of age or older and has a diagnosis of moderate to severely active rheumatoid arthritis AND
    1. Member has previously received a biologic or synthetic DMARD (tofacitinib) indicated for moderately to severely active rheumatoid arthritis OR  
    2. Member has experienced an inadequate response to at least a 3-month trial of conventional DMARD (i.e. hydroxychloroquine, leflunomide, methotrexate, or sulfalazine) OR
    3. Member has an intolerance or contraindication to conventional DMARDs
Polyarticular Juvenile Idiopathic Arthritis
Member is 2 years of age or older and has a diagnosis of polyarticular juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for polyarticular juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to conventional DMARD (methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine) OR
    3. Member has involvement of high-risk joints (cervical spine, wrist, or hip), high disease activity, and/or is at high risk of disabling joint damage that warrants a biologic as first line therapy
Systemic Juvenile Idiopathic Arthritis
Member is 2 years of age or older and has a diagnosis of systemic juvenile idiopathic arthritis AND
    1. Member has previously received a biologic for systemic juvenile idiopathic arthritis OR
    2. Member has had an inadequate response to at least a three-month trial of NSAIDs OR
    3. Member has had an inadequate response to at least a three-month trial of methotrexate or leflunomide
Cytokine Release Syndrome
Member will be using for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome
 
Giant Cell Arteritis is administered by subcutaneous injection and is not covered on the medical benefit. Please see pharmacy benefit.
 
Dosage and Administration
 
The recommended intravenous dose of Tocilizumab (ActemraTM) is based on indication:
Rheumatoid Arthritis- 4mg/kg every four weeks followed by an increase to 8mg/kg every 4 weeks based on clinical response. Doses exceeding 800mg per infusion are not recommended.
Polyarticular Juvenile Idiopathic Arthritis- 10mg/kg every four weeks in patients less than 30kg and 8mg/kg every four weeks in patients at or above 30kg
Systemic Juvenile Idiopathic Arthritis- 12mg/kg every two weeks in patients less than 30kg and 8mg/kg every two weeks in patients at or above 30kg
Cytokine Release Syndrome- 12mg/kg in patients less than 30kg and 8mg/kg in patients at or above 30kg. Up to three additional doses of Tocilizumab (ActemraTM) may be administered. Doses exceeding 800mg per infusion are not recommended.
 
Tocilizumab (ActemraTM) intravenous infusion is available in 80mg, 200mg, or 400mg single-dose vials. Tocilizumab (ActemraTM) subcutaneous injection is available in a 162mg prefilled syringe or a 162mg single-dose prefilled ACTPen auto injector.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Tocilizumab (ActemraTM) does not meet member benefit certificate primary coverage criteria for any of the following:
    • Any other indication not included above OR
    • In combination with biological DMARDs such as TNF antagonist, IL-1R antagonist, or anti-CD20 monoclonal antibodies OR
    • Tuberculosis, other active serious infections, or a history of recurrent infections OR  
    • Individual has not had a tuberculin skin test (TST) or a Centers for Disease Control (CDC-) and Prevention -recommended equivalent to evaluate for latent tuberculosis prior to initiating Tocilizumab (ActemraTM)
 
For members with contracts without primary coverage criteria, the use of Tocilizumab (ActemraTM) in any other condition than listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Rationale:
Tocilizumab intravenous infusion was approved for rheumatoid arthritis based on the efficacy and safety of five randomized, double-blind, multicenter studies in patients 18 years of age or older with active rheumatoid arthritis.
 
In Study 1 Tocilizumab was given intravenously every four weeks as monotherapy in patients who had not been treated with methotrexate within 24 weeks prior to randomization. 67% of these patients were methotrexate naïve. Patients received 8mk/kg Tocilizumab monotherapy or methotrexate alone. The primary endpoint was the number of patients who achieved an ACR 20 response at Week 24. At Week 24 53% of methotrexate patients and 70% of Tocilizumab treated patients achieved an ACR 20 response.
 
In Study 2 patients received 4mg/kg of Tocilizumab, 8mg/kg of Tocilizumab, or placebo intravenously once every four weeks. Each treatment arm was given in combination with methotrexate. All of these patients had previously experienced an inadequate clinical response to methotrexate. At Week 24 27% of placebo patients, 51% of 4mg/kg dosing Tocilizumab patients, and 56% of 8mg/kg dosing Tocilizumab patients achieved an ACR 20 response.
 
Study 3 also evaluated patients who had an inadequate clinical response to methotrexate. Patients received 4mg/kg of Tocilizumab, 8mg/kg of Tocilizumab, or placebo intravenously once every four weeks in combination with methotrexate. At Week 24 27% of placebo patients, 48% of 4mg/kg dosing Tocilizumab patients, and 59% of 8mg/kg dosing Tocilizumab patients achieved an ACR 20 response.
 
Study 4 evaluated patients who had an inadequate response to one or more DMARD. Patients received 8mg/kg Tocilizumab or placebo intravenously once every four weeks in combination with a DMARD. At Week 24 24% of placebo patients and 61% of Tocilizumab patients achieved an ACR 20 response.
 
Study 5 evaluated patients who had an inadequate clinical response or were intolerant to one or more TNF antagonist therapies. The TNF antagonist was discontinued prior to randomization. Patients received 4mg/kg of Tocilizumab, 8mg/kg of Tocilizumab, or placebo intravenously once every four weeks in combination with methotrexate. At Week 24 10% of placebo patients, 30% of 4mg/kg dosing Tocilizumab patients, and 50% of 8mg/kg dosing Tocilizumab patients achieved an ACR 20 response.
 
In all intravenous studies, patients treated with 8 mg/kg Tocilizumab had higher ACR 20, ACR 50, and ACR 70 response rates versus MTX- or placebo-treated patients at week 24. During the 24 week controlled portions of Studies 1 to 5, patients treated with Tocilizumab at a dose of 4 mg/kg in patients with inadequate response to DMARDs or TNF antagonist therapy had lower response rates compared to patients treated with Tocilizumab 8 mg/kg. (Actemra, 2020)
 
Tocilizumab intravenous infusion was approved for polyarticular juvenile idiopathic arthritis based on the safety and efficacy of a three-part study. Patients two to seventeen years of age with polyarticular juvenile idiopathic arthritis who had an inadequate response or inability to tolerate methotrexate were included in the study. Patients had a least six months of active disease and were allowed to continue the use of methotrexate. Other DMARDs or biologics were not permitted in the study.
 
Part I consisted of a 16-week active Tocilizumab treatment lead-in period. Patients weighing less than 30kg were given either Tocilizumab 8mg/kg or 10mg/kg intravenously once every four weeks. At the end of Part I, 91% of patients taking methotrexate plus Tocilizumab and 83% of patients taking Tocilizumab monotherapy achieved an ACR 30 response compared to baseline. Part II consisted of a 24-week randomized double-blind placebo controlled withdrawal period. Patients were randomized to Tocilizumab or placebo. The primary end point was the proportion of patients with an ACR 30 flare at week 40 relative to week 16. Tocilizumab treated patients experienced significantly fewer disease flares compared to placebo-treated patients, 26% versus 48%. Part III consisted of a 64-week open-label period.  
 
Tocilizumab intravenous infusion was approved for systemic juvenile idiopathic arthritis based on a 12-week randomized, double blind, placebo-controlled study. 112 patients were randomized. 75 patients received Tocilizumab every two weeks at either 8mg/kg for patients at or above 30kg or 12mg/kg for patients less than 30kg. 37 patients received placebo every two weeks. The primary endpoint was the proportion of patients with at least 30% improvement in JIA ACR 30 response. At week 12 91% of patients receiving Tocilizumab and 24% of patients receiving placebo had a ACR 30 response.
 
Tocilizumab intravenous infusion was approved for cytokine release syndrome based on a retrospective analysis of pooled outcome data from clinical trials of CAR T-cell therapies for hematological malignancies. Patients had been treated with Tocilizumab 8mk/kg (12mg/kg for patients less than 30kg) with or without additional high-dose corticosteroids for severe or life-threatening CRS. 45 patients were evaluated. 31 patients (69%) achieved a response.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2021.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Subcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA).
 
Patients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration, minimum concentration, area under the curve over a dosing interval, and mean concentration of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy.
 
In 24 patients, the median (range) age was 65.5 (57-90) years, and 62.5% were female. TCZ exposures were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study.
 
Both doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The maximum concentration and mean concentration achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and Ctrough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks. (Schmitt C, Brockwell L, Giraudon M, 2022)
CPT/HCPCS:
J3262Injection, tocilizumab, 1 mg
J3590Unclassified biologics
Q5133Injection, tocilizumab-bavi (tofidence), biosimilar, 1 mg
Q5135Injection, tocilizumab aazg (tyenne), biosimilar, 1 mg
References: Actemra [prescribing information]. South San Francisco, CA: Genentech, Inc. May 2020

Fraenkel L, Bathon JM, England BR, et. al.(2021) American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis & Rheumatology. 2021 Jul;73(7):1108-23.

Fraenkel L, et.al.(2021) American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care & Research. 2021; 73(7) 924-939.

Kimura Y, Schanberg LE, Tomlinson GA, et. al.(2021) Optimizing the start time of biologics polyarticular juvenile idiopathic arthritis: a comparative effectiveness study of Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans. Arthritis & Rheumatology. 2021 Oct;73 (10):1898-909.

Onel KB, Horton DB, Lovell DJ, et. al.(2021) American College of Rheumatology guideline for treatment juvenile idiopathic arthritis: therapeutic approaches for oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis. Arthritis & Rheumatology. 2022 Apr;74(4):553-69.

Ringold S, Angeles-Han S, Beukelman T, et al.(2019) 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. American College of Rheumatology. 2019;1-18.

Ringold S, Weiss PF, Beukelman T, et al.(2013) Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for the Medical Therapy of Children With Systemic Juvenile Idiopathic Arthritis Arthritis & Rheumatism. 2013;65:2499-2512

Singh JA, Saag KG, Bridges SL Jr, et al.(2016) 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatology. 2016;68(1)1-26.

Tocilizumab: Actemra [package insert]. San Francisco (CA): Genentech, 2022
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.