ACTEMRA (tocilizumab) Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as Description defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as Criteria defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS, BLUE SHIELD and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. O628.11.docx Page 1 of 11
Description: Actemra is an interleukin-6 (IL-6) receptor inhibitor that is used to treat rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis (SJIA), polyarticular juvenile idiopathic arthritis (PJIA), giant cell arteritis (GCA) and cytokine release syndrome (CRS). Definitions: Adult: Age 18 years and older Preferred Tumor Necrosis Factor (TNF) Inhibitor Medications: Enbrel Humira Remicade O628.11.docx Page 2 of 11
Criteria: Effective 02/01/17: For site of service requirements for Actemra (tocilizumab), see BCBSAZ Medical Coverage Guideline #O1008, Site of Service Requirements for Certain Medications. See Resources section for FDA-approved dosage. Actemra is considered medically necessary with documentation of ALL of the following: 1. ONE of the following: For treatment of individuals 18 years of age and older with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDS). For treatment of active systemic juvenile idiopathic arthritis in individuals 2 years of age and older For treatment of active polyarticular juvenile idiopathic arthritis in individuals 2 years of age and older 2. Failure of, contraindication to or intolerance to TWO of the preferred TNF inhibitor medications Enbrel, Humira, Remicade, (refer to, Small Molecules and Biologics Chart #AP94 Administrative Procedure Guideline for the preferred medication(s) labeled indications) 1. 3. No known hypersensitivity to Actemra 4. No concurrent treatment with any other biological DMARDs such as TNF antagonists, IL-1R (interleukin 1) antagonists, anti-cd-20 monoclonal antibodies or co-stimulation modulators as listed in Drug Facts and Comparisons 2 5. No evidence of active infection, including any localized infections 6. Absolute neutrophil count (ANC) is equal to or greater than 2,000 per mm cubed 3 7. Platelet count is equal to or greater than 100,000 per mm cubed 3 8. ALT (alanine aminotransferase) or AST (aspartate aminotransferase) is equal to or less than 1.5 times the upper limit of normal 3 9. No active hepatic disease or hepatic impairment 10. Live vaccines will not be given concurrently with Actemra 4 11. Individual has been previously evaluated for tuberculosis risk factors and tested for latent infection and treatment with standard anti-mycobacterial medication(s) is initiated, if indicated, prior to the initiation of Actemra O628.11.docx Page 3 of 11
Criteria: (cont.) Actemra for individuals 18 years of age and older with giant cell arteritis is considered medically necessary with documentation of ALL of the following: 1. No known hypersensitivity to Actemra 2. No concurrent treatment with any other biological DMARDs such as TNF antagonists, IL-1R (interleukin 1) antagonists, anti-cd-20 monoclonal antibodies or co-stimulation modulators as listed in Drug Facts and Comparisons 2 3. No evidence of active infection, including any localized infections 4. Absolute neutrophil count (ANC) is equal to or greater than 2,000 per mm cubed 3 5. Platelet count is equal to or greater than 100,000 per mm cubed 3 6. ALT (alanine aminotransferase) or AST (aspartate aminotransferase) is equal to or less than 1.5 times the upper limit of normal 3 7. No active hepatic disease or hepatic impairment 8. Live vaccines will not be given concurrently with Actemra 4 9. Individual has been previously evaluated for tuberculosis risk factors and tested for latent infection and treatment with standard anti-mycobacterial medication(s) is initiated, if indicated, prior to the initiation of Actemra Actemra for individuals 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome is considered medically necessary with documentation of ALL of the following: 1. No known hypersensitivity to Actemra 2. No concurrent treatment with any other biological DMARDs such as TNF antagonists, IL-1R (interleukin 1) antagonists, anti-cd-20 monoclonal antibodies or co-stimulation modulators as listed in Drug Facts and Comparisons 2 3. No evidence of active infection, including any localized infections 4. Absolute neutrophil count (ANC) is equal to or greater than 2,000 per mm cubed 3 5. Platelet count is equal to or greater than 100,000 per mm cubed 3 6. ALT (alanine aminotransferase) or AST (aspartate aminotransferase) is equal to or less than 1.5 times the upper limit of normal 3 7. No active hepatic disease or hepatic impairment 8. Live vaccines will not be given concurrently with Actemra 4 9. Individual has been previously evaluated for tuberculosis risk factors and tested for latent infection and treatment with standard anti-mycobacterial medication(s) is initiated, if indicated, prior to the initiation of Actemra O628.11.docx Page 4 of 11
Criteria: (cont.) Actemra for all other indications not previously listed or if above criteria not met is considered experimental or investigational based upon: 1. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 2. Insufficient evidence to support improvement of the net health outcome, and 3. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives. These indications include, but are not limited to: Treatment with dosing or frequency outside the FDA-approved dosing and frequency 1 Not applicable for current members on Actemra prior to 07/09/14 or new members who are actively being treated with Actemra prior to their effective date with BCBSAZ. (Excludes any changes in route of administration, such as changing intravenous delivery to subcutaneous delivery). 2 This concomitant regimen is not recommended by the Actemra manufacturer. Actemra can be used alone or in combination with methotrexate and, in RA, with other non-biologic DMARDs. 3 Ongoing monitoring of these laboratory parameters during Actemra therapy is recommended by the manufacturer. 4 Live vaccines should not be given concurrently with Actemra as clinical safety has not been established. No data are available on the secondary transmission of infection from individuals receiving live vaccines to individuals receiving Actemra. No data are available on the effectiveness of vaccination in individuals receiving Actemra. Because IL-6 inhibition may interfere with the normal immune response to new antigens, it is recommended that all individuals, particularly systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis individuals, if possible, be brought up-to-date with all recommended immunizations prior to initiation of Actemra therapy. O628.11.docx Page 5 of 11
Resources: Literature reviewed 02/01/18. We do not include marketing materials, poster boards and nonpublished literature in our review. 1. American College of Rheumatology, Saag KG, Teng GG, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008 Jun 15 2008;59(6):762-784. 2. American College of Rheumatology, Singh JA, Furst DE, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis care & research. May 2012;64(5):625-639. 3. American College of Rheumatology, Singh JA, Saag KG, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis care & research. Jan 2016;68(1):1-25. 4. Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series. Swiss medical weekly. Jan 17 2011;141:w13156. 5. Unizony S, Arias-Urdaneta L, Miloslavsky E, et al. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis care & research. Nov 2012;64(11):1720-1729. 6. UpToDate.com. Treatment of Giant Cell (Temporal) Arteritis. 09/14/2016. 7. Villiger PM, Adler S, Kuchen S, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet (London, England). May 07 2016;387(10031):1921-1927. O628.11.docx Page 6 of 11
Resources: (cont.) Actemra Package Insert: - FDA-approved indication and dosage: Indication Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs Recommended Dose Actemra may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs. Actemra is administered by intravenous drip infusion or subcutaneously. Recommended intravenous (IV) dosage: When used in combination with DMARDs or as monotherapy the recommended intravenous starting dose is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. Reduction of dose from 8mg per kg to 4 mg per kg is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia and thrombocytopenia 1. Doses exceeding 800 mg per infusion are not recommended in RA patients. Recommended subcutaneous (SC) dosage: Patients less than 100 kg weight: 162 mg SC every other week, followed by an increase to every week based on clinical response. Patients at or above 100 kg weight: 162 mg SC every week. 1 See product labeling for reduction of dose recommendations for certain dose related laboratory changes. O628.11.docx Page 7 of 11
Resources: (cont.) Actemra Package Insert: (cont.) - FDA-approved indication and dosage: (cont.) Indication Patients 2 years of age and older with active systemic juvenile idiopathic arthritis (SJIA) Recommended Dose Actemra may be used alone or in combination with methotrexate. The recommended doses are given once every 2 weeks. Actemra is administered by intravenous drip infusion. Subcutaneous administration is not approved for SJIA. Patients less than 30 kg weight: 12 mg per kg Patients at or above 30 kg weight: 8 mg per kg A change in dose should not be made based solely on a single visit body weight measurement, as weight may fluctuate. Interruption of dosing may be needed for management of doserelated laboratory abnormalities including elevated liver enzymes, neutropenia and thrombocytopenia 2. 2 See product labeling for interruption of dosing for management of dose-related laboratory abnormalities. Patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA) Actemra may be used alone or in combination with methotrexate. The recommended doses are given once every 4 weeks. Actemra is administered by intravenous drip infusion. Subcutaneous administration is not approved for PJIA. Patients less than 30 kg weight: 10 mg per kg. Patients at or above 30 kg weight: 8 mg per kg. A change in dose should not be made based solely on a single visit body weight measurement, as weight may fluctuate. Interruption of dosing may be needed for management of doserelated laboratory abnormalities including elevated liver enzymes, neutropenia and thrombocytopenia 3. 3 See product labeling for interruption of dosing for management of dose-related laboratory abnormalities. O628.11.docx Page 8 of 11
Resources: (cont.) Actemra Package Insert: (cont.) - FDA-approved indication and dosage: (cont.) Indication Adult patients with giant cell arteritis (GCA) Recommended Dose Actemra is administered subcutaneously. Intravenous administration is not approved for GCA. Recommended subcutaneous (SC) dosage: 162 mg SC every week in combination with a tapering course of glucocorticoids. 162 mg SC every other week in combination with a tapering course of glucocorticoids may be prescribed based on clinical considerations. Actemra may be used alone following discontinuation of glucocorticoids. Interruption of dosing may be needed for management of doserelated laboratory abnormalities including elevated liver enzymes, neutropenia and thrombocytopenia 4. 4 See product labeling for interruption of dosing for management of dose-related laboratory abnormalities. Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or lifethreatening cytokine release syndrome Actemra is administered by intravenous drip infusion. Subcutaneous administration is not approved for CRS. Recommended intravenous dosage: Patients less than 30 kg weight: 12 mg per kg. Patients at or above 30 kg weight: 8 mg per kg. Actemra may be used alone or in combination with corticosteroids. If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, up to 3 additional doses of Actemra may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CRS patients. O628.11.docx Page 9 of 11
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability or sex, you can file a grievance with: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 509F, HHH Building, Washington, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O628.11.docx Page 10 of 11
Multi-Language Interpreter Services: (cont.) O628.11.docx Page 11 of 11