Drug and Biologic Coverage Policy

Effective Date ...... 1/1/2021 Next Review Date ...... 1/1/2022 Coverage Policy Number ...... M0004

Tocilizumab Intravenous

Table of Contents Related Coverage Resources

Overview ...... 1 COVID-19 Drug/Biologic Therapeutics Coverage Policy ...... 1 Immunomodulators – Oral and Subcutaneous FDA Approved Indications ...... 3 (Employer Group Benefit Plans) Recommended Dosing ...... 3 Immunomodulators – Oral and Subcutaneous General Background ...... 5 (Individual and Family Plans) Coding/Billing Information ...... 7 Oncology References ...... 7

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Overview This coverage policy addresses the use of intravenous (Actemra®) for non-oncology indications. The use of tocilizumab for oncology indications is addressed in a separate coverage policy (Oncology Medications). Please refer to the related coverage policy links above. Coverage Policy

Tocilizumab intravenous (Actemra®) is considered medically necessary when any of the following criteria are met: • Chimeric (CAR) -induced severe or life-threatening release syndrome (CRS) OR cytokine release syndrome (CRS) associated with COVID-19

• Inflammatory Arthritis Associated with Therapy and ALL of the following: o Documented failure or intolerance, contraindication per FDA label, intolerance, or not a candidate for ONE steroid (for example, methylprednisolone, ) o Individual developed inflammatory arthritis while receiving a checkpoint inhibitor (for example, Keytruda ( IV infusion), Opdivo ( IV infusion), Yervoy ( IV infusion), Tecentriq ( IV infusion), Bavencio ( IV infusion), Imfinzi ( IV infusion)) Page 1 of 8 Drug and Biologic Coverage Policy: M0004 o Prescribed by, or in consultation with a rheumatologist or an oncologist

• Polyarticular Juvenile Idiopathic Arthritis (PJIA) and BOTH of the following: o Individual is 2 years of age or older o Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in PJIA

• and BOTH of the following: o Documented failure or inadequate response, contraindication per FDA label, intolerance, or not a candidate for ONE disease-modifying anti-rheumatic drug (DMARD) (for example, , , sulfasalazine)† † NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a DMARD. o Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in rheumatoid arthritis

• Still’s Disease and ALL of the following o Documented failure or intolerance, contraindication per FDA label, intolerance, or not a candidate to ONE (for example, prednisone)† o Documented failure or intolerance, contraindication per FDA label, intolerance, or not a candidate to ONE conventional synthetic disease-modifying antirheumatic drug (DMARD) (for example, methotrexate) given for at least 2 months† † NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a steroid or a conventional synthetic DMARD. o Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in Still’s Disease

• Systemic Juvenile Idiopathic Arthritis (SJIA) and the following: o Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in Systemic Juvenile Idiopathic Arthritis (SJIA)

For Chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) OR cytokine release syndrome (CRS) associated with COVID-19, authorization is for 1 week (4 doses only)

For all other covered uses, initial authorization is up to 12 months.

Tocilizumab intravenous (Actemra) is considered medically necessary for continued use when the individual has had a positive response to tocilizumab intravenous.

Reauthorization for up to 12 months.

When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy.

Tocilizumab intravenous (Actemra) is considered experimental, investigational or unproven for ANY other use including the following: • Concomitant use with any other biologic including all non- (non-TNF) biologics, anti-TNF biologics, or oral immunomodulatory agents (for example, Otezla or Xeljanz/ Xeljanz XR) • Crohn’s Disease

Note: Receipt of sample product does not satisfy any criteria requirements for coverage.

Page 2 of 8 Drug and Biologic Coverage Policy: M0004 FDA Approved Indications

Rheumatoid Arthritis (RA) Actemra (tocilizumab) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

Giant Cell Arteritis (GCA) – subcutaneous only Actemra (tocilizumab) is indicated for the treatment of (GCA) in adult patients.

Polyarticular Juvenile Idiopathic Arthritis (PJIA) Actemra (tocilizumab) is indicated for the treatment of active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.

Systemic Juvenile Idiopathic Arthritis (SJIA) Actemra (tocilizumab) is indicated for the treatment of active systemic juvenile idiopathic arthritis in patients 2 years of age and older.

Cytokine Release Syndrome (CRS) Actemra (tocilizumab) is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

Recommended Dosing

FDA Recommended Dosing Rheumatoid Arthritis Actemra may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion or as a subcutaneous injection.

Recommended Intravenous Dosage Regimen: The recommended dosage of Actemra for adult patients given as a 60-minute single intravenous drip infusion 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 8 mg per kg to 4 mg per kg is recommended for management of certain dose- related laboratory changes including elevated liver enzymes, , and [see Dosage and Administration (2.9), Warnings and Precautions (5.3), and Adverse Reactions (6.1)]. • Doses exceeding 800 mg per infusion are not recommended in RA patients [see Clinical Pharmacology (12.3)].

Recommended Subcutaneous Dosage Regimen: Patients less than 100 kg weight 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response Patients at or above 100 kg weight 162 mg administered subcutaneously every week

When transitioning from Actemra to subcutaneous administration administer the first subcutaneous dose instead of the next scheduled intravenous dose.

Interruption of dose or reduction in frequency of administration of subcutaneous dose from every week to every other week dosing is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration (2.9), Warnings and Precautions (5.3), and Adverse Reactions (6.2)].

Giant Cell Arteritis

Page 3 of 8 Drug and Biologic Coverage Policy: M0004 The recommended dose of Actemra for adult patients with GCA is 162 mg given once every week as a subcutaneous injection in combination with a tapering course of glucocorticoids.

A dose of 162 mg given once every other week as a subcutaneous injection in combination with a tapering course of glucocorticoids may be prescribed based on clinical considerations.

Actemra can be used alone following discontinuation of glucocorticoids. • Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration (2.9)]. • Intravenous administration is not approved for GCA.

Polyarticular Juvenile Idiopathic Arthritis Actemra may be used alone or in combination with methotrexate. Do not change dose based solely on a single visit body weight measurement, as weight may fluctuate.

Recommended Intravenous Dosage Regimen: The recommended dosage of Actemra for PJIA patients given once every 4 weeks as a 60-minute single intravenous drip infusion is: Recommended Intravenous PJIA Dosage Every 4 Weeks Patients less than 30 kg weight 10 mg per kg Patients at or above 30 kg weight 8 mg per kg

Recommended Subcutaneous Dosage Regimen: Recommended Subcutaneous PJIA Dosage Patients less than 30 kg weight 162 mg once every 3 weeks Patients at or above 30 kg weight 162 mg once every 2 weeks

When transitioning from Actemra intravenous therapy to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose.

Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration (2.9)].

Systemic Juvenile Idiopathic Arthritis Actemra may be used as an intravenous infusion or as a subcutaneous injection alone or in combination with methotrexate. Do not change a dose based solely on a single visit body weight measurement, as weight may fluctuate.

Recommended Intravenous Dosage Regimen: The recommended dose of Actemra for SJIA patients given once every 2 weeks as a 60-minute single intravenous drip infusion is:

Recommended Intravenous SJIA Dosage Every 2 Weeks Patients less than 30 kg weight 12 mg per kg Patients at or above 30 kg weight 8 mg per kg

Recommended Subcutaneous Dosage Regimen: Recommended Subcutaneous SJIA Dosage Patients less than 30 kg weight 162 mg once every two weeks Patients at or above 30 kg weight 162 mg once every week

When transitioning from Actemra intravenous therapy to subcutaneous administration, administer the first subcutaneous dose when the next scheduled intravenous dose is due.

Page 4 of 8 Drug and Biologic Coverage Policy: M0004 Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration (2.9)].

Cytokine Release Syndrome (CRS) Use only the intravenous route for treatment of CRS. The recommended dose of Actemra for treatment of CRS given as a 60-minute intravenous infusion is: Recommended Intravenous CRS Dosage Patients less than 30 kg weight 12 mg per kg Patients at or above 30 kg weight 8 mg per kg Alone or in combination with

• 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. • Subcutaneous administration is not approved for CRS

General Considerations for Administration • Actemra has not been studied in combination with biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal and selective co-stimulation modulators because of the possibility of increased and increased risk of . Avoid using Actemra with biological DMARDs. • It is recommended that Actemra not be initiated in patients with an absolute neutrophil count (ANC) below 2000 per mm3, platelet count below 100,000 per mm3, or who have ALT or AST above 1.5 times the upper limit of normal (ULN). o Patients with severe or life-threatening CRS frequently have cytopenias or elevated ALT or AST due to the lymphodepleting or the CRS. The decision to administer Actemra should take into account the potential benefit of treating the CRS versus the risks of short-term treatment with Actemra.

General Background

Pharmacology Targeting IL-6 is a therapeutic option for treatment of chronic inflammatory diseases such as RA. (Schoels, 2013) IL-6 has been shown to be involved in diverse physiological processes and is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as RA. Actemra is an IL-6 receptor monoclonal that binds to soluble and membrane-bound IL-6 receptors and has been shown to inhibit IL-6-mediated signaling through these receptors.1 In CRS (reported in 79% to 94% of patients receiving CAR T therapy), there are high levels of IL-6; therefore, IL-6 signaling is inhibited with Actemra IV. (Actemra Prescribing Information, 2018, Yescarta Prescribing Information, 2017, Kymriah Prescribing Information, 2017, Lee, 2014, NCCN/ASCO, 2019)

Professional Societies/Organizations NCCN and American Society of Clinical Oncology (ASCO) NCCN has guidelines in partnership with the American Society of Clinical Oncology (ASCO) [version 1.2019 – November 14, 2018] for Management of -Related Toxicities. (NCCN/ASCO, 2019) In regard to CAR-T-cell-related toxicities, prompt and urgent attention is required to prevent progression. All patients with Grade 2, 3, and 4 are recommended for treatment with Actemra. In patients with Grade 1 CRS, Actemra is also listed as a therapeutic option for prolonged CRS in patients with significant symptoms and/or comorbidities. For inhibitor-related toxicities, or Actemra may be considered for refractory or severe arthritis not responding to steroids and anti-inflammatory agents.

American College of

Page 5 of 8 Drug and Biologic Coverage Policy: M0004 The 2011 ACR recommendations for the treatment of JIA (published prior to the approval of Actemra IV for PJIA) propose initial DMARD treatment with MTX in most patients; however, sulfasalazine is recommended for patients with enthesitis-related arthritis and may also be used in certain patients with sacroiliac arthritis. (Beukelman, 2011)

Updated guidelines from the American College of Rheumatology (ACR) for treatment of SJIA (2013) mention Actemra as a second- or third-line agent in patients with active systemic features and varying degrees of synovitis and in patients without active systemic features and varying degrees of synovitis; NSAIDs, systemic glucocorticoids, Kineret, TNFis, and MTX are among other treatment options. (Ringold, 2013)

Guidelines from the American College of Rheumatology (ACR) [2015] have TNF inhibitors and non-TNF biologics (such as Actemra) equally positioned as a recommended therapy following a trial of a conventional synthetic DMARD (e.g., MTX, leflunomide, hydroxychloroquine, sulfasalazine). (Ito, 2004)

® The American Board of Internal Medicine’s (ABIM) Foundation Choosing Wisely Initiative: The American College of Rheumatology Choosing Wisely® (2013) recommends a 3 month trial of methotrexate (or another conventional non-biologic DMARD) unless contraindicated or other exceptions (e.g., high disease activity and poor prognostic features) before initiating biologic therapy for rheumatoid arthritis.

Centers for Medicare & Medicaid Services - National Coverage Determinations (NCDs) There are no CMS National Coverage Determinations for tocilizumab intravenous.

Other Uses with Supportive Evidence Still’s disease presents in adults with features similar to those of SJIA.11 Actemra IV has been effective in reducing fever, symptoms, and markers of in patients who were refractory to treatment with prednisone, MTX, Kineret, and/or a TNF antagonist.11-20 Prospective, randomized, controlled trials are needed.

Other Uses without Supportive Evidence There is insufficient evidence in the peer-reviewed published scientific literature to support safety and efficacy of tocilizumab in .

Concurrent Use with a Biologic or with a Targeted Synthetic DMARD. Data are lacking evaluating concomitant use of Actemra IV another biologic or with a targeted synthetic DMARD used for an inflammatory condition. Combination therapy is generally not recommended due to a higher rate of AEs with combinations and lack of data supportive of additional efficacy. (Furst, 2012, Xeljanz Prescribing Information, 2017) Note: This does NOT exclude the use of conventional synthetic DMARDs (e.g., MTX, leflunomide, hydroxychloroquine, and sulfasalazine) in combination with Actemra IV. Please note that this table is not all inclusive.

Brand (generic name) Mechanism of Action Cimzia ( for SC injection) Inhibition of TNF Enbrel ( for SC injection) Inhibition of TNF Erelzi™ (etanercept-szzs for SC injection) Inhibition of TNF Humira® ( for SC injection) Inhibition of TNF Amjevita™ (adalimumab-atto for SC injection) Inhibition of TNF Cyltezo® (adalimumab-adbm for SC injection) Inhibition of TNF Simponi® ( for SC injection) Inhibition of TNF Simponi® Aria™ (golimumab for IV infusion) Inhibition of TNF Remicade® (infliximab for IV infusion) Inhibition of TNF Inflectra™ (infliximab-dyyb for IV infusion) Inhibition of TNF Renflexis® (infliximab-abda for IV infusion) Inhibition of TNF Actemra® (tocilizumab for IV infusion) Inhibition of IL-6 Actemra® (tocilizumab for SC injection) Inhibition of IL-6 Kevzara™ ( for SC injection) Inhibition of IL-6 Orencia® ( for IV infusion) T-cell costimulation modulator Orencia® (abatacept for SC injection) T-cell costimulation modulator Rituxan® ( for IV infusion) CD20-directed cytolytic antibody

Page 6 of 8 Drug and Biologic Coverage Policy: M0004 Truxima® (rituximab-abbs IV injection) CD20-directed cytolytic antibody Kineret® ( for subcutaneous SC injection) Inhibition of IL-1 Stelara® ( for SC injection) Inhibition of IL-12/23 Stelara® (ustekinumab for IV infusion) Inhibition of IL-12/23 Siliq™ ( SC injection) Inhibition of IL-17 Cosentyx™ ( for SC injection) Inhibition of IL-17A Taltz® ( for SC injection) Inhibition of IL-17A Ilumya™ (-asmn for SC injection) Inhibition of IL-23 Skyrizi™ ( SC injection) Inhibition of IL-23 Tremfya® ( for SC injection) Inhibition of IL-23 Entyvio™ ( IV infusion) receptor antagonist Otezla® ( tablets) Inhibition of PDE4 Xeljanz®, Xeljanz XR ( tablets, tofacitinib extended-release Inhibition of the JAK pathways tablets) SC – Subcutaneous; TNF – Tumor necrosis factor; IL – ; IV – Intravenous; PDE4 – Phosphodiesterase 4; JAK – .

Crohn’s Disease In a 12-week pilot study conducted in Japan, 36 adults with active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] ≥ 150 and increased CRP) were randomized, in a double-blind fashion to Actemra 8 mg/kg IV every 2 weeks; or alternating infusions of Actemra 8 mg/kg IV every 4 weeks and (i.e., alternating with placebo every 2 weeks), or to placebo every 2 weeks. (Ito, 2004) At baseline the CDAI means ranged from 287 to 306. Patients had been treated with corticosteroids, mesalamine-type drugs, metronidazole, or elemental diet. Six patients in the placebo group, four patients on Actemra IV every 4 weeks and one patient on Actemra IV every 2 weeks dropped out. The mean reduction in the CDAI score in the Actemra 8 mg/kg IV every 2 week group was 88 points (from mean 306 to 218). Further studies are needed.

Coding/Billing Information

Note: 1) This list of codes may not be all-inclusive. 2) Deleted codes and codes which are not effective at the time the service is rendered may not be eligible for reimbursement.

Considered Medically Necessary when criteria in the applicable policy statements listed above are met:

HCPCS Description Codes J3262 Injection, tocilizumab, 1 mg

References

1. American College of Rheumatology: Don’t prescribe biologics for rheumatoid arthritis before a trial of methotrexate (or other conventional non-biologic DMARDs). Choosing Wisely. Accessed March 8, 2019. Available at URL address: http://www.choosingwisely.org/clinician-lists/american-college-rheumatology- biologics-for-rheumatoid-arthritis/ 2. Actemra® injection for intravenous infusion [prescribing information]. South San Francisco, CA: ; December 2018. 3. Beukelman T, Patkar NM, Saag KG, et al. 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 (Hoboken). 2011;63(4):465-482. 4. De Bandt M, Saint-Marcoux B. Tocilizumab for multirefractory adult-onset Still's disease. Ann Rheum Dis. 2009;68(1):153-154. 5. Furst DE, Keystone EC, So AK, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Ann Rheum Dis. 2013;72 Suppl 2:ii2-34.

Page 7 of 8 Drug and Biologic Coverage Policy: M0004 6. Genentech, Inc.. Actemra (tocilizumab) [product information]. South San Francisco, CA: Genentech, Inc.; December 2018. 7. Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a anti-interleukin-6 receptor in active Crohn’s disease. Gastroenterology. 2004;126:989-996. 8. Iwamoto M, Nara H, Hirata D, et al. Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still's disease. Arthritis Rheum. 2002;46(12):3388-3389. 9. Kymriah™ suspension for intravenous infusion [prescribing information]. East Hanover, NJ: Novartis Oncology; August 2017. 10. Matsumoto K, Nagashima T, Takatori S, et al. Glucocorticoid and cyclosporine refractory adult onset Still's disease successfully treated with tocilizumab. Clin Rheumatol. 2009;28(4):485-487. 11. McEvoy GK, ed. AHFS 2019 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists, Inc. 2019. 12. Nakahara H, Mima T, Yoshio-Hoshino N, et al. A case report of a patient with refractory adult-onset Still's disease who was successfully treated with tocilizumab over 6 years. Mod Rheumatol. 2009;19(1):69-72. 13. NCCN/ASCO Management of Immunotherapy-Related Toxicities (Immune Checkpoint Inhibitor-Related Toxicities) Clinical Practice Guidelines in Oncology (Version 1.2019 – November 14, 2018). © 2018 National Comprehensive Network, Inc. Available at: http://www.nccn.org. Accessed March 4, 2019. 14. Perdan-Pirkmajer K, Praprotnik S, Tomšič M. A case of refractory adult-onset Still's disease successfully controlled with tocilizumab and a review of the literature. Clin Rheumatol. 2010;29(12):1465-1467. 15. Puéchal X, de Bandt M, Berthelot JM, et al. Tocilizumab in refractory adult Still's disease. Arthritis Care Res (Hoboken). 2011;63(1):155-159. 16. Rech J, Ronneberger M, Englbrecht M, et al. Successful treatment of adult-onset Still's disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade. Ann Rheum Dis. 2011;70(2):390-392. 17. 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. Arthritis & Rheumatism. 2013;65(10):2499-2512. 18. Riera E, Olivé A, Narváez J, et al. Adult onset Still's disease: review of 41 cases. Clin Exp Rheumatol. 2011;29(2):331-336. 19. Sabnis GR, Gokhale YA, Kulkarni UP. Tocilizumab in Refractory Adult-Onset Still's Disease with Aseptic Meningitis-Efficacy of Interleukin-6 Blockade and Review of the Literature. Semin Arthritis Rheum. 2011;40(4):365-368. 20. 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. 21. Singh JA, Saag KG, Bridges L Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2016;68(1):1-26. 22. Smolen JS, Landewe R, Breedvel FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492-509. doi:10.1136. 23. Xeljanz® tablets [prescribing information]. New York, NY: Inc; February 2016. 24. Yescarta™ suspension for intravenous infusion [prescribing information]. Santa Monica, CA: Kite Pharma; October 2017. 25. Yoshimura M, Makiyama J, Koga T, et al. Successful treatment with tocilizumab in a patient with refractory adult-onset Still's disease (AOSD). Clin Exp Rheumatol. 2010;28(1):141-142.

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