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Tocilizumab (e.g., Actemra™) | |
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Description: |
Regulatory Status
Tocilizumab (e.g., ActemraTM) is approved by the U.S. Food and Drug Administration (FDA) for the following indications:
Coding
See CPT/HCPCS Code section below.
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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 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:
CONTINUED APPROVAL for up to 1 year:
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
CONTINUED APPROVAL for up to 1 year:
SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
CYTOKINE RELEASE SYNDROME
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 1 year:
Policy Guidelines
Examples of Contraindications to Methotrexate:
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
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
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
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
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
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
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
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:
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):
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
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
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
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):
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
Polyarticular Juvenile Idiopathic Arthritis
Member is 2 years of age or older and has a diagnosis of polyarticular juvenile idiopathic arthritis AND
Systemic Juvenile Idiopathic Arthritis
Member is 2 years of age or older and has a diagnosis of systemic juvenile idiopathic arthritis AND
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:
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.
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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 endopoint 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.
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CPT/HCPCS: | |
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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 |
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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 © 2024 American Medical Association. |