Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Tocilizumab (Actemra®) for Intravenous Infusion

Policy #:08.00.85i



The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Tocilizumab (Actemra®) for intravenous infusion is considered medically necessary and, therefore, covered for the following indications when, for each individual indication, all of the associated criteria are met:

Castleman's Disease (CD)
  • In one of the following conditions, as a single agent:
    • Multicentric CD: Subsequent therapy for multicentric CD that has progressed following treatment of relapsed/refractory or progressive disease
    • Unicentric CD: Second-line therapy for individuals with relapsed or refractory disease who are human immunodeficiency virus--negative and human herpesvirus-8--negative
  • Active or latent tuberculosis (TB) has been ruled out

Cytokine release syndrome (CRS) caused by chimeric antigen receptor (CAR) T cell therapy (e.g., tisagenlecleucel [Kymriah®], axicabtagene ciloleucel [Yescarta®])
  • In individuals two years of age or older
  • When used alone or in combination with corticosteroids
  • When used for the following Grades, per National Cancer Institute's Common Terminology criteria for Adverse Events (CTCAE v5.0) Grading System*:
    • Grade 1 CRS: For prolonged (>3 days) CRS in individuals with significant symptoms and/or comorbidities
    • Grade 2-4 CRS
  • Active or latent tuberculosis (TB) has been ruled out
  • When used up to a maximum of four doses

Cytokine release syndrome (CRS), caused by blinatumomab (Blincyto®) therapy in individuals with acute lymphoblastic leukemia
  • In individuals two years of age or older
  • When refractory to corticosteroids
  • Active or latent tuberculosis (TB) has been ruled out
  • When used up to a maximum of four doses

Graft-versus-host disease (GVHD), acute, after hematopoietic cell transplantation
  • In conjunction with systemic corticosteroids and/or immunosuppressive agent following no response (steroid-refractory disease) to first-line therapy options
  • Active or latent tuberculosis (TB) has been ruled out

Inflammatory arthritis, severe, immunotherapy-related, caused by Immune Checkpoint Inhibitors (e.g., ipilimumab [Yervoy], nivolumab [Opdivo], pembrolizumab [Keytruda])
  • There is documentation of inadequate response, intolerance, or contraindication to two weeks of high-dose corticosteroids
  • Active or latent tuberculosis (TB) has been ruled out

Neurotoxicity caused by chimeric antigen receptor (CAR) T cell therapy (e.g., tisagenlecleucel [Kymriah®], axicabtagene ciloleucel [Yescarta®]) in individuals with concurrent cytokine release syndrome (CRS)
  • Grade* 1-4 neurotoxicity as additional single-dose therapy if individual has concurrent cytokine release syndrome (CRS)
  • When used up to a maximum of four doses
  • Active or latent tuberculosis (TB) has been ruled out

Polyarticular juvenile idiopathic arthritis (PJIA), active
  • In individuals two years of age or older
  • Active or latent tuberculosis (TB) has been ruled out
  • When used alone or in combination with methotrexate
  • There is documentation of inadequate response, intolerance, or contraindication to non-biologic disease-modifying anti-rheumatic drugs (DMARDs) (e.g., methotrexate)

Rheumatoid arthritis
  • Moderately to severely active disease
  • In individuals 18 years of age or older
  • Active or latent tuberculosis (TB) has been ruled out
  • When used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs)
  • There is documentation of inadequate response, intolerance, or contraindication to a 3-month trial of one or more DMARDs
  • For individuals who have not previously received a biologic DMARD to treat adult rheumatoid arthritis, tocilizumab (Actemra®) for intravenous infusion is only eligible for coverage when the individual has a documented failure, contraindication, or intolerance to infliximab (Remicade®) or golimumab (Simponi Aria®), or there is a clinical reason that a trial of infliximab (Remicade®) or golimumab (Simponi Aria®) would be otherwise inappropriate for the individual.

Systemic juvenile idiopathic arthritis (Still's disease), active
  • In individuals two years of age or older
  • Active or latent tuberculosis (TB) has been ruled out
  • When used alone or in combination with methotrexate
  • There is documentation of inadequate response, intolerance, or contraindication to nonsteroidal anti-inflammatory drugs (NSAIDS), corticosteroids, or (DMARDs e.g., leflunomide, methotrexate)

* See Guidelines Section for Grading Tables for CRS and neurotoxicity

EXPERIMENTAL/INVESTIGATIONAL

All other uses for tocilizumab (Actemra®) for intravenous infusion are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

BILLING REQUIREMENTS

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration.
  • To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, tocilizumab (Actemra®) for intravenous infusion is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

CONSIDERATION FOR ADMINISTRATION

Tocilizumab (Actemra®) for intravenous infusion has not been studied, and its use should be avoided in combination with biological disease-modifying antirheumatic drugs (DMARDs) such as tumor necrosis factor (TNF) antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, and selective co-stimulation modulators, due to the increased possibility of immunosuppression and increased risk of infection.

THE NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE v5.0) GRADING SYSTEM*

Cytokine release syndrome (CRS)*
Grade 1Fever with or without constitutional symptoms
Grade 2Hypotension responding to fluids; hypoxia responding to <40% O2
Grade 3Hypotension managed with one pressor; hypoxia requiring ≥ 40% O2
Grade 4Life-threatening consequences; requiring ventilator support or vasopressor-refractory shock
Grade 5Death

CAR T-cell-related Neurotoxicity*
Grade 1Mild impact on activities of daily living (ADLs)
Grade 2Moderate impact on ADLs
Grade 3Severe impact on ADLs; seizure; signs of elevated intracranial pressure (e.g., papilledema, Cushing's triad, hypertension, bradycardia)
Grade 4Critical condition and/or obtunded and cannot perform assessment of tasks; repetitive seizures without return to baseline or life-threatening seizures (non-convulsive or convulsive)

*Sources:
  • National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Management of Immunotherapy-Related Toxicities. V.1.2020. 12/16/19.
  • National Institutes of Health. Common Terminology criteria for Adverse Events (CTCAE v5.0) Grading System.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on January 8, 2010, for treatment of adults with moderately to severely active rheumatoid arthritis, after at least one TNF antagonist has been tried and failed. On October 11, 2012, based on the safety and efficacy outcomes from further Phase III and post-marketing studies, the FDA expanded the approval for the treatment of adult individuals with moderately to severely active RA who have had an inadequate response to one or more DMARDs.

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on April 15, 2011, for treatment of individuals ages two and older with active systemic juvenile idiopathic arthritis, also known as Still's disease.

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on April 29, 2013, for the treatment of individuals ages two and older with active polyarticular juvenile idiopathic arthritis (PJIA).

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on August 30, 2017, for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric individuals two years of age and older.

Description

Tocilizumab (Actemra®) for intravenous infusion, a humanized monoclonal antibody, inhibits the interleukin-6 receptor that binds specifically to both the soluble and membrane-bound interleukin-6 receptors, thereby blocking the inflammatory response.

ACTIVE RHEUMATOID ARTHRITIS

Tocilizumab (Actemra®) for intravenous infusion was approved by the US Food and Drug Administration (FDA) on January 8, 2010, for the treatment of adult individuals with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. In phase II and phase III clinical trials, tocilizumab (Actemra®), when used in combination with methotrexate or alone, has been shown to be effective in reducing the signs and symptoms of RA in individuals who had an inadequate response to TNF antagonists.

On October 11, 2012, based on the safety and efficacy outcomes from further Phase III and post-marketing studies, the FDA expanded the approval for the treatment of adult individuals with moderately to severely active RA who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). These studies showed a statistically significant greater percentage of individuals achieving ACR20 at Week 24 with the use of tocilizumab (Actemra®) for intravenous infusion plus a DMARD when compared to the placebo plus a DMARD.

RA is a chronic inflammatory autoimmune disorder that involves inflammation of the synovial joints and can result in erosion of cartilage and bone. The American College of Rheumatology's guidelines for the treatment of RA recommend that newly diagnosed individuals with RA begin treatment with DMARDs. DMARDs act to slow down disease progression, and some act with mild chemotherapeutic action, causing immunosuppression.

Furthermore, DMARDs can be subdivided into the traditional small-molecular-mass, chemically synthesized non-biologic DMARDs (such as, but not limited to, methotrexate, sulfasalazine, azathioprine, leflunomide, hydroxychloroquine sulfate, and cyclosporine) and the newer biologic DMARDs. Examples of biologic DMARDs include, but are not limited to, etanercept (Enbrel®), adalimumab (Humira®), anakinra (Kineret®), abatacept (Orencia®), rituximab (Rituxan®), and infliximab (Remicade®).

Tocilizumab (Actemra®) for intravenous infusion is administered by intravenous infusion in adults once every four weeks over 60 minutes.

SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on April 15, 2011, for the treatment of individuals ages two years and older with active systemic juvenile idiopathic arthritis (SJIA), also known as Still's disease. SJIA is a rare, potentially life-threatening disease in children that causes severe inflammation throughout the body. The occurrence of fever spikes; rash; swelling and inflammation of the lymph nodes, liver, and spleen; and high white blood cell and platelet counts differentiate SJIA from other juvenile idiopathic forms of arthritis. The prevalence of juvenile idiopathic arthritis is estimated to be 1 to 2 per 1,000 children, and SJIA affects about 10 percent of all juvenile idiopathic arthritis patients.

Tocilizumab (Actemra®) for intravenous infusion was used in an international, multi-center controlled trial of 112 individuals with SJIA, ages two to 17 years of age, who had inadequate clinical response to nonsteriodal anti-inflammatory drugs or corticosteroids or methotrexate due to toxicity or lack of efficacy. Eighty-five percent of those who received tocilizumab (Actemra®) for intravenous infusion responded to treatment, compared to 24 percent of individuals who received the placebo. Response was defined as at least a 30 percent improvement in the American College of Rheumatology's juvenile idiopathic arthritis efficacy variables, as well as the absence of fever in the preceding seven days. However, among those who received tocilizumab (Actemra®), there were three cases of macrophage-activation syndrome, a potentially fatal complication of childhood systemic inflammatory disorders.

Tocilizumab (Actemra®) for intravenous infusion is administered by intravenous infusion in individuals two years of age and older once every two weeks over 60 minutes, and may be administered alone or in combination with methotrexate.

POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on April 29, 2013 for the treatment of individuals ages two years and older with active polyarticular juvenile idiopathic arthritis (PJIA). PJIA is a subset of juvenile idiopathic arthritis (JIA) and comprises 20 to 30 percent of all patients with JIA. The diagnosis of PJIA is made when five or more joints are affected in the first six months after disease onset. Management of PJIA may include medications such as corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs), or DMARDs, including immunomodulators or biologic agents.

Tocilizumab (Actemra®) for intravenous infusion was investigated in a three-part trial of 188 individuals with active PJIA, ages two to 17 years of age, who had inadequate clinical response to methotrexate or were intolerant to methotrexate. Part I was a 16-week, open-label trial of tocilizumab (Actemra®), followed by Part II, which was a 24-week randomized double-blind placebo-controlled withdrawal period. Finally, Part III was a 64-week open-label extension.

In Part I, response to treatment was defined as at least a 30 percent improvement in the American College of Rheumatology's (ACR) juvenile idiopathic arthritis efficacy variables. After 16 weeks of therapy, 91% and 83% of patients, respectively, achieved an ACR 30 response compared to baseline, while receiving concomitant methotrexate or on tocilizumab (Actemra®) for intravenous infusion monotherapy. ACR 50/70 responses were 84% and 64%, respectively, for patients receiving concomitant methotrexate, and 80% and 55%, respectively, for patients on tocilizumab (Actemra®) for intravenous infusion monotherapy.

Those who achieved an ACR 30 response (n=163) entered Part II of the study, where patients were randomized to tocilizumab (Actemra®) for intravenous infusion or placebo (1:1 ratio). The results of this study reported that those receiving tocilizumab (Actemra®) for intravenous infusion experienced significantly fewer disease flares compared to placebo-treated patients (26% versus 48%). Also, more patients treated with tocilizumab (Actemra®) for intravenous infusion showed ACR 30/50/70 responses at Week 40 compared to patients withdrawn to placebo.

Tocilizumab (Actemra®) for intravenous infusion is administered by intravenous infusion in individuals two years of age and older once every four weeks over 60 minutes, and may be administered alone or in combination with methotrexate.

CYTOKINE RELEASE SYNDROME (CRS)

Cytokine release syndrome (CRS) occurs when immune-based chemotherapy or introduction of immune cells, such as chimeric antigen receptor (CAR) T cells, cause an abnormally large activation of the cells involved in the immune system (e.g., lymphoctyes or myeloid cells) which then release inflammatory cytokines. Symptoms of CRS may develop within minutes, hours, or days after the infusion. Symptoms range from mild to severe or life-threatening and may include fever, hypotension, mental status changes, tachycardia; worsening of respiratory distress, including pulmonary infiltrates, increasing oxygen requirements, or need for mechanical ventilation; organ toxicity; and seizures. The severity of CRS is defined in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) grading system, where a score of one is non-life threatening (e.g., fever, nausea) and a score of five is death.

Tocilizumab (Actemra®) for intravenous infusion was approved by the FDA on August 30, 2017 for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening CRS in adults and pediatric patients two years of age and older.

The efficacy of tocilizumab (Actemra®) for severe or life-threatening CRS was reviewed in a retrospective analysis of pooled outcome data from clinical trials of CAR T cell therapies for hematological malignancies. Forty-five patients received tocilizumab (Actemra®) 8 mg/kg (12 mg/kg for patients < 30 kg) with or without additional high-dose corticosteroids. The analysis only reviewed the first episode of CRS in each patient. The median time from start of CRS to first dose of tocilizumab was four days (range, 0–18 days). Resolution of CRS was defined as lack of fever and off vasopressors for at least 24 hours. Patients were considered responders if CRS resolved within 14 days of the first dose of tocilizumab, no more than two doses of tocilizumab were needed, and no drugs other than tocilizumab and corticosteroids were used for treatment. The results of this review concluded that 31 patients (69%) achieved a clinical response to the first CRS episode.

Tocilizumab (Actemra®) for intravenous infusion is administered by intravenous infusion in individuals two years of age and older over 60 minutes. A maximum dose of 800 mg per infusion is recommended. A maximum of four doses administered at least eight hours apart may be prescribed, if necessary. Tocilizumab (Actemra®) for intravenous infusion may be administered alone or in combination with corticosteroids.

SAFETY

Tocilizumab (Actemra®) for intravenous infusion should be interrupted if an individual develops a serious infection or an opportunistic infection or sepsis, until the infection is controlled. Other safety concerns that require monitoring during tocilizumab (Actemra®) for intravenous infusion therapy are elevated liver enzymes, elevated low-density lipoproteins or bad cholesterol, hypertension, and gastrointestinal perforations.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

American Hospital Formulary Service (AHFS). Drug Information 2020. Tocilizumab (Actemra®). [Lexicomp Online Web site]. Last modified: 12/11/2015. Available at: ://online.lexi.com/lco/action/home [via subscription only]. Accessed March 27, 2020.


Axicabtagene ciloleucel (Yescarta). Kite Pharma, Inc.: Santa Monica, CA. Prescribing Information. 05/2019. Available at: https://www.yescarta.com/. Accessed March 27, 2020.

Beukelman T, Patkar N, Saag K. 2011 American College of Rheumatology Recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011;63(4):465-482.

Brunner HI, Ruperto N, Zuber Z, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course Juvenile Idiopathic Arthritis: data from a Phase 3 trial. Presented at the American College of Rheumatology Annual Scientific Meeting in Washington, D.C.; November 9-14, 2012. ACR Oral presentation; ACR Abstract #1597.

DeBenedetti, Fabrizio, Brunner, et al. Tocilizumab in patients with systemic juvenile idiopathic arthritis: efficacy data from the placebo-controlled 12-week part of the phase 3 TENDER trial [abstract]. Arthritis Rheum. 2010;62(Suppl 10):1434.

Elsevier’s Clinical Pharmacology Compendium. Tocilizumab (Actemra®). 03/24/2020. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 27, 2020.

Frey N. Cytokine release syndrome: Who is at risk and how to treat. Best Pract Res Clin Haematol. 2017;30(4):336-340.

Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58(10):2968-80.

Jain T, Litzow MR. No free rides: management of toxicities of novel immunotherapies in ALL, including financial. Hematology Am Soc Hematol Educ Program. 2018(1):25-34.

Kremer JL, Blanco R, Brzosko M, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate at 1 year: The LITHE study. Arthritis Rheum. 2010; Epub.

Larsen RA. Treatment of relapsed or refractory acute lymphoblastic leukemia in adults. [UpToDate Web site]. 04/12/19. Available at: https://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-adults?source=search_result&search=cytokine%20release%20syndrome&selectedTitle=5~119 [via subscription only]. Accessed March 30, 2020.

Lexi-Drugs Compendium. Tocilizumab (Actemra®). 03/27/2020. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 27, 2020.

Kimura Y. Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis. UpToDate. 07/12/18. Available at: https://www.uptodate.com/contents/systemic-juvenile-idiopathic-arthritis-clinical-manifestations-and-diagnosis?source=search_result&search=Systemic%20juvenile%20idiopathic%20arthritis&selectedTitle=2~150 [via subscription only] . Accessed March 27, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Acute Lymphoblastic Leukemia. V.1.2020. 01/15/20. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf [via free subscription]. Accessed March 27, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-Cell Lymphomas. V.1.2020. 01/22/20. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via free subscription]. Accessed March 27, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Hematopoietic Cell Transplantation: Pre-transplant receipient evaluation and management of graft versus host disease. V.2.2020. 03/23/20. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf [via free subscription]. Accessed March 27, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Management of Immunotherapy-Related Toxicities. V.1.2020. 12/16/19. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf [via free subscription]. Accessed March 27, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Tocilizumab. [NCCN Web site]. 2020. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed March 27, 2020.

National Institutes of Health. Common Terminology criteria for Adverse Events (CTCAE v5.0) Grading System. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm . Accessed March 27, 2020.

Novitas Solutions, Inc. Article (A53127) For Self-Administered Drug Exclusion List. [Novitas Medicare Services Web site]. Original: 10/01/2015, Revised: 12/02/2019. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53127&ver=88&name=331*1&UpdatePeriod=855&bc=AAAAEAAAAAAA& . Accessed March 20, 2020.

Novitas Solutions, Inc. FUTURE Article (A53127) For Self-Administered Drug Exclusion List. [Novitas Medicare Services Web site]. Original: 10/01/2015, Revised: 05/03/2020. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53127&ver=96&name=331*1&UpdatePeriod=877&bc=AAAACAAAAAAA& . Accessed March 23, 2020.

Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019;71(6):717-734.

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 and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65(10):2499-512.

Schoels MM, van der Heijde D, Breedveld FC, et al. Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement. Ann Rheum Dis. 2013; 72(4): 583–589.

Singh JA, Furst DE, Bharat A, 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 Res (Hoboken). 2012;64(5):625-39.

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

Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987-9.

Tisagenlecleucel (Kymriah). Novartis Pharmaceuticals Corporation:
East Hanover, NJ. Prescribing Information. 05/2018. Available at: https://www.hcp.novartis.com/products/kymriah/ . Accessed March 27, 2020.

Tocilizumab (Actemra®). Genentech Inc. Prescribing Information. 06/2019. Available at: http://www.gene.com/gene/products/information/actemra/pdf/pi.pdf . Accessed March 27, 2020.

Truven Health Analytics. Micromedex® DrugDex® Compendium. DrugDex®. Tocilizumab (Actemra®). [Micromedex® Solutions Web site]. 03/25/2020. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 27, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Product Labeling. [FDA Web site]. Blinatumomab (Blincyto®) 03/2020; ipilimumab (Yervoy) 03/2020; nivolumab (Opdivo) 03/2020; pembrolizumab (Keytruda) 01/2020; tocilizumab (Actemra®) 06/2019. Available at:
https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed March 27, 2020.

Weiss PF. Polyarticular juvenile idiopathic arthritis: Treatment. UpToDate. 01/19/2020. Available at: https://www.uptodate.com/contents/polyarticular-juvenile-idiopathic-arthritis-treatment?search=polyarticular-juvenile-idiopathic-arthritis-treatmen&source=search_result&selectedTitle=2~19&usage_type=default&display_rank=2 [via subscription only]. Accessed March 27, 2020.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A for ICD-10 Codes and Narratives


HCPCS Level II Code Number(s)

J3262 Injection, Tocilizumab, 1mg


Revenue Code Number(s)


N/A



Misc Code

:


THE FOLLOWING MODIFIER IS USED WHEN REPORTING
Tocilizumab (Actemra®) for Intravenous Infusion

JA Intravenous administration




Coding and Billing Requirements

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration.
  • To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.
Cross References

Attachment A: Tocilizumab (Actemra®) for Intravenous Infusion
Description: ICD-10 CODES AND NARRATIVES




Policy History

REVISIONS FROM 08.00.85i:
06/08/2020This version of the policy will become effective 06/08/2020.

This policy was updated with the following changes:

The addition of two indications, according to National Comprehensive Cancer Network (NCCN):
  • Cytokine release syndrome (CRS), caused by blinatumomab (Blincyto®) therapy in individuals with acute lymphoblastic leukemia
  • Graft-versus-host disease (GVHD), acute, after hematopoietic cell transplantation. ICD-10 Diagnosis code: D89.810 Acute graft-versus-host disease

The addition of coverage criteria for Polyarticular juvenile idiopathic arthritis (PJIA) regarding prior use or consideration of non-biologic disease-modifying anti-rheumatic drugs (DMARDs) (e.g., methotrexate), according to US Food and Drug Administration (FDA) and Ringold et al 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis.

The addition of coverage criteria for previous consideration/use of DMARDs (e.g., leflunomide, methotrexate) for systemic juvenile idiopathic arthritis (Still's disease), according to Ringold 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 and tuberculosis screening among children receiving biologic medications.

A Billing Requirement was added to this policy regarding the Coding Modifier: JA Intravenous administration.

REVISIONS FROM 08.00.85h:
04/22/2019This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN). The coverage criteria for Castleman's Disease and Neurotoxicity caused by chimeric antigen receptor (CAR) T cell therapy have been added to this policy. The coverage criteria have been revised for Cytokine release syndrome caused by chimeric antigen receptor (CAR) T cell therapy.

REVISIONS FROM 08.00.85g:
12/19/2018This policy has been reissued in accordance with the Company's annual review process.
11/15/2017This policy has been updated to communicate the Company's coverage criteria for tocilizumab (Actemra®) for the treatment of cytokine release syndrome (CRS).


Effective 10/05/2017 this policy has been updated to the new policy template format.
Version Effective Date: 06/08/2020
Version Issued Date: 06/08/2020
Version Reissued Date: N/A



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