Kevzara (sarilumab)

Policy Number: 5.01.640 Last Review: 10/2020 Origination: 10/2017 Next Review: 10/2021

Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Kevzara (sarilumab) when it is determined to be medically necessary because the criteria shown below are met.

When Policy Topic is covered Kevzara is considered medically necessary in the treatment of rheumatoid arthritis in adults after the following steps have been met:

Step 1 - at least a 12-week treatment course each of 2 preferred products (Cimzia, Humira, Simponi, or Xeljanz) has not been effective.

AND

Step – 2 - at least a 12-week course of therapy with BOTH Actemra and Orencia has not been effective.

When Policy Topic is not covered Kevzara is considered investigational when used for all other conditions, including, but not limited to:

Kevzara has not been shown to be effective, or there are limited or preliminary data or potential safety concerns that are not supportive of general approval for the following conditions. Rationale for non- coverage for these specific conditions is provided below. (Note: This is not an exhaustive list of Conditions Not Recommended for Approval.)

1. Ankylosing Spondylitis (AS). In a Phase II study, Kevzara did not demonstrate efficacy in patients with AS.5

2. Concurrent use with a Biologic or with a Targeted Synthetic DMARD. Kevzara should not be administered in combination with another biologic or with a targeted synthetic DMARD used for an inflammatory condition. Combination therapy is generally not recommended due to a potential for a higher rate of adverse effects with combinations and lack of evidence for additive efficacy.6-7 Note: This does NOT exclude the use of conventional synthetic DMARDs (e.g., MTX, leflunomide, hydroxychloroquine, and sulfasalazine) in combination with Actemra IV.

Considerations Kevzara requires prior authorization through the Clinical Pharmacy Department.

This Blue Cross and Blue Shield of Kansas City policy Statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers.

Description of Procedure or Service Kevzara for subcutaneous (SC) injection is a recombinant humanized interleukin-6 (IL-6) receptor inhibitor.1 IL-6 is a pro-inflammatory cytokine that is involved in various physiologic processes. Kevzara has demonstrated efficacy and is indicated for the treatment of rheumatoid arthritis (RA) in adults with moderate to severe active RA who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs).1-2 Kevzara + conventional synthetic (cs)DMARD has demonstrated superior efficacy over placebo + csDMARD as assessed by American College of Rheumatology (ACR) responses, physical function, and radiographic progression.

Boxed Warnings Kevzara has boxed warnings concerning risks of serious infection.1 Prior to initiating therapy, patients should be evaluated for active tuberculosis (TB) infection, and periodically during therapy patients should be assessed for latent TB infection. If a serious infection develops, treatment with Kevzara should be interrupted until infection is controlled.

Rationale There are multiple drugs available to treat inflammatory conditions, including another IL-6 blocker (Actemra [tocilizumab IV infusion, tocilizumab SC injection]), tumor necrosis factor inhibitors (TNFis) [e.g., Cimzia® {certolizumab pegol SC injection}, etanercept SC injection [e.g., Enbrel®, Erelzi™], adalimumab SC injection [e.g., Humira®, Amjevita™], infliximab IV infusion [e.g., Remicade®, Inflectra™, Renflexis®], Simponi® {golimumab SC injection}, Simponi Aria® {golimumab IV infusion}], other IL blockers (e.g., Cosentyx® [secukinumab SC injection], Stelara® [ustekinumab IV infusion, ustekinumab SC injection], Siliq® [brodalumab SC injection], and Taltz® [ixekizumab SC injection]), and other non- TNF biologics (e.g., Kineret® [anakinra SC injection], Orencia® [abatacept IV infusion, abatacept SC injection], Rituxan® [rituximab IV infusion], Entyvio™ [vedolizumab IV infusion]). There are also targeted synthetic DMARDs available (e.g., Xeljanz®/XR [tofacitinib tablets/extended-release tablets] and Otezla® [apremilast tablets]) which are indicated for certain inflammatory conditions. Conventional synthetic DMARDs (e.g., MTX, leflunomide, sulfasalazine) are also commonly utilized for management of certain inflammatory conditions.

Kevzara is indicated for the treatment of adults with moderate to severe active RA who have had an inadequate response or intolerance to at least one DMARD.1 It can be used alone or in combination with MTX or other non-biologic DMARDs. Guidelines from the ACR (2015) were published prior to the approval of Kevzara; however, these guidelines have TNFis and non-TNF biologics (i.e., Actemra, Orencia, Rituxan), administered with or without MTX, equally positioned as a recommended therapy following a trial of a conventional synthetic DMARD (e.g., MTX, leflunomide, hydroxychloroquine, sulfasalazine).4

References 1. Kevzara™ injection [prescribing information]. 2. Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a Phase III study. Arthritis Rheumatol. 2015;67(6):1424-1437. 3. Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290. 4. 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. 5. Sieper J, Braun J, Kay J, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2015;74(6):1051-1057. 6. 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. 7. Xeljanz® tablets [prescribing information]. New York, NY: Pfizer Inc; February 2016.

Billing Coding/Physician Documentation Information NA Kevzara (sarilumab) is a pharmacy benefit; specialty

Additional Policy Key Words 5.01.640

Policy Implementation/Update Information 10/2017 New policy titled Kevzara (sarilumab) 10/2018 Policy reviewed – no changes made 09/2019 Added Rinvoq to the preferred step requirements 10/2019 Annual review – no changes made 01/2020 Policy updated to be consistent with Optum step changes, added step 2 criteria and changed the preferred agents listed under step 1 10/2020 Annual review – no changes made

State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.