Clinical UM Guideline

 

Subject: Clinically Equivalent Cost Effective Services – Targeted Immune Modulators
Guideline #:  CG-ADMIN-02 Publish Date:    06/06/2018
Status: Revised Last Review Date:    05/03/2018

Description

This document addresses targeted immune modulators (TIMs) that are considered clinically equivalent cost effective services.

Note: Please see the following related documents for additional information:

Clinically Equivalent Cost Effective Targeted Immune Modulators

When a TIM is determined to be medically necessary based on the clinical criteria in the applicable document listed in the Note in the Description section above, the benefit plan may have in addition a medically necessary criterion that the service be cost effective.  When such language exists, the benefit plan may determine which TIM is covered.  

A benefit plan may select any one or more of the following as a clinically equivalent cost effective TIM: adalimumab (Humira), abatacept (Orencia), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi, Simponi Aria), infliximab (Remicade), tocilizumab (Actemra), ixekizumab (Taltz), secukinumab (Cosentyx), ustekinumab (Stelara), rilonacept (Arcalyst), canakinumab (Ilaris), sarilumab (Kevzara), guselkumab (Tremfya), vedolizumab (Entyvio), tildrakizumab-asmn (Ilumya).  A list of one or more cost effective TIM agents is available here.

In benefit plans where there is a requirement to use a cost effective TIM agent, requests for a TIM agent that is not cost effective may be approved when the following criteria are met:

  1. Rheumatoid Arthritis
    1. Individual has been receiving and is maintained on a stable dose of the requested non-cost-effective agent; or
    2. The individual has had a trial and inadequate response or is intolerant to up to two (2) cost-effective agents:
      1. Cost-effective agents: Actemra, Cimzia, Enbrel, Humira, Kevzara, Orencia, Remicade, Simponi, Simponi Aria;
        Note: One cost-effective agent(s) must include a tumor necrosis factor inhibitor (TNFi);
        or
    3. The cost-effective agent is not acceptable due to concomitant clinical conditions, such as but not limited to any of the following:
      1. Known hypersensitivity to any active or inactive component which is not also associated with the requested non-cost-effective agent; or
      2. Individual’s age; or
      3. Pregnant or planning to become pregnant; or
      4. Serious infections or concurrent sepsis;
        or
    4. If the requested agent is a biologic non-tumor necrosis factor inhibitor (TNFi) (such as but not limited to, Actemra, Kevzara, or Orencia) and there is no designated cost-effective non-TNFi agent for the prescribed indication, a non-cost-effective biologic non-TNFi agent may be approved for either concomitant clinical condition:
      1. Demyelinating disease; or
      2. Heart failure with documented left ventricular dysfunction;
        or
    5. The cost-effective agent(s) do not have activity against a concomitant clinical condition (for example: Crohn’s disease) and the requested non-cost-effective agent does.  
  2. Plaque Psoriasis or Psoriatic Arthritis
    1. Individual has been receiving and is maintained on a stable dose of the requested non-cost-effective agent; or
    2. The individual has had a trial and inadequate response or is intolerant to up to two (2) cost-effective agents;
      1. Cost-effective agents: Cimzia, Cosentyx, Enbrel, Humira, Ilumya, Orencia, Remicade, Simponi, Simponi Aria, Stelara, Taltz, Tremfya.
      2. Non-cost-effective agents: Siliq.
        Note: One cost-effective agent(s) must include a tumor necrosis factor inhibitor (TNFi);
        or
    3. The cost-effective agent is not FDA-approved for the indication under consideration or does not meet the off-label drug use criteria of CG-DRUG-01 Off-Label Drug and Approved Orphan Drug Use (see below) and the requested non-cost-effective agent does;
      or
    4. The cost effective agent is not acceptable due to concomitant clinical conditions, such as but not limited to any of the following:
      1. Known hypersensitivity to any active or inactive component which is not also associated with the requested non-cost effective agent; or
      2. Individual’s age; or
      3. Pregnant or planning on becoming pregnant; or
      4. Serious infections or concurrent sepsis;
        or
    5. If the requested agent is a biologic non-tumor necrosis factor inhibitor (TNFi) (such as but not limited to, Cosentyx, Ilumya, Orencia, Stelara, Taltz, Tremfya) and there is no designated cost-effective non-TNFi agent for the prescribed indication, a non-cost-effective biologic non-TNFi agent may be approved for either concomitant clinical condition:
      1. Demyelinating disease; or
      2. Heart failure with documented left ventricular dysfunction;
        or
    6. The cost-effective agent(s) do not have activity against a concomitant clinical condition (for example, Crohn’s disease or ulcerative colitis) and the requested non-cost-effective agent does.  
  3. Crohn’s Disease or Ulcerative Colitis
    1. Individual has been receiving and is maintained on a stable dose of the requested non-cost-effective agent; or
    2. The individual has had a trial and inadequate response or is intolerant to one (1) cost-effective agent;
      1. Cost-effective agents: Entyvio, Humira, Remicade, Simponi, Stelara.
      2. Non-cost-effective agents: Cimzia.
        Note: Remicade must be selected as one of the cost-effective agents;
        or
    3. The cost-effective agent is not FDA-approved for this indication or does not meet the off-label drug use criteria of CG-DRUG-01 Off-Label Drug and Approved Orphan Drug Use (see below) and the requested non-cost-effective agent does;
      or
    4. The cost-effective agent is not acceptable due to concomitant clinical conditions, such as but not limited to any of the following:
      1. Known hypersensitivity to any active or inactive component which is not also associated with the requested non-cost effective agent; or
      2. Individual’s age; or
      3. Pregnant or planning on becoming pregnant; or
      4. Serious infections or concurrent sepsis;
        or
    5. If the requested agent is a biologic non-tumor necrosis factor inhibitor (TNFi) (such as but not limited to, Entyvio or Stelara) and there is no designated cost-effective non-TNFi agent for the prescribed indication, a non-cost-effective biologic non-TNFi agent may be approved for either concomitant clinical condition:
      1. Demyelinating disease; or
      2. Heart failure with documented left ventricular dysfunction; or
      3. Malignancy (such as but not limited to, solid or hematologic cancers and excluding superficial skin cancers [such as basal and squamous cell]); or
      4. Tuberculosis infection;
        or
    6. The cost-effective agent(s) do not have activity against a concomitant clinical condition (for example, plaque psoriasis or rheumatoid arthritis) and the requested non-cost-effective agent does.
  4. Other Indications
    1. Individual has been receiving and is maintained on a stable dose of the requested non-cost-effective agent; or
    2. The individual has had a trial and inadequate response or is intolerant to up to two (2) cost effective agents;
      1. Cost-effective agents: Actemra, Arcalyst, Cimzia, Cosentyx, Enbrel, Humira, Ilaris, Orencia, Remicade, Simponi, Simponi Aria.
        Note: One cost-effective agents must include a tumor necrosis factor inhibitor (TNFi);
        or
    3. The cost-effective agent is not FDA-approved for the indication under consideration or does not meet the off-label drug use criteria of CG-DRUG-01 Off-Label Drug and Approved Orphan Drug Use (see below) and the requested non-cost-effective agent does;
      or
    4. The cost-effective agent is not acceptable due to concomitant clinical conditions, such as but not limited to any of the following:
      1. Known hypersensitivity to any active or inactive component which is not also associated with the requested non-cost-effective agent; or
      2. Individual’s age; or
      3. Pregnant or planning on becoming pregnant; or
      4. Serious infections or concurrent sepsis;
        or
    5. If the requested agent is a biologic non-tumor necrosis factor inhibitor (TNFi) (such as but not limited to, Actemra, Arcalyst, Cosentyx, Ilaris, Orencia) and there is no designated cost-effective non-TNFi agent for the prescribed indication, a non-cost-effective biologic non-TNFi agent may be approved for either concomitant clinical condition:
      1. Demyelinating disease; or
      2. Heart failure with documented left ventricular dysfunction.

FDA-approved Indications or Indications Meeting off-label drug use criteria of CG-DRUG-01 Off-Label Drug and Approved Orphan Drug Use

 

aHUS

AS

CD

CRS

GCA

HS

MCD

MG

PFS

PJIA

PNH

Ps

PsA

SJIA

RA

UC

UV

Abatacept (Orencia)

 

 

 

 

 

 

 

 

 

X*

 

 

X

 

X

 

 

Adalimumab (Humira)

 

X

X*

 

 

X

 

 

 

X*

 

X

X

Y*

X

X

X*

Brodalumab (Siliq)

 

 

 

 

 

 

 

 

 

 

 

X

 

 

 

 

 

Canakinumab (Ilaris)

 

 

 

 

 

 

 

 

X* FCAS, MWS, TRAPS, HIDS/

MKD, FMF

 

 

 

 

X*

 

 

 

Certolizumab pegol (Cimzia)

 

X

X

 

 

 

 

 

 

 

 

 

X

 

X

 

 

Eculizumab (Soliris)

X*

 

 

 

 

 

 

X

 

 

X*

 

 

 

 

 

 

Vedolizumab (Entyvio)

 

 

X

 

 

 

 

 

 

 

 

 

 

 

 

X

 

Etanercept (Enbrel)

 

X

 

 

 

 

 

 

 

X*

 

X*

X

Y*

X

 

 

Golimumab (Simponi Aria)

 

X

 

 

 

 

 

 

 

 

 

 

X

 

X

 

 

Golimumab (Simponi)

 

X

 

 

 

 

 

 

 

 

 

 

X

 

X

X

 

Guselkumab (Tremfya)

 

 

 

 

 

 

 

 

 

 

 

X

 

 

 

 

 

Infliximab (Remicade)

 

X

X*

 

 

 

 

 

 

Y*

 

X

X

Y*

X

X*

Y*

Ixekizumab (Taltz)

 

 

 

 

 

 

 

 

 

 

 

X

X

 

 

 

 

Rilonacept (Arcalyst)

 

 

 

 

 

 

 

 

X* FCAS, MWS

 

 

 

 

 

 

 

 

Sarilumab (Kevzara)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

X

 

 

Secukinumab (Cosentyx)

 

X

 

 

 

 

 

 

 

 

 

X

X

 

 

 

 

Tildrakizumab-asmn

(Ilumya)

 

 

 

 

 

 

 

 

 

 

 

X

 

 

 

 

 

Tocilizumab (Actemra)

 

 

 

X*

X

 

Y

 

 

X*

 

 

 

X*

X

 

 

Ustekinumab (Stelara)

 

 

X

 

 

 

 

 

 

 

 

X*

X

 

 

 

 

X = FDA-approved Indications (excluding cosmetic indications)
Y = Indications Meeting off-label drug use criteria of CG-DRUG-01 Off-Label Drug and Approved Orphan Drug Use
*Includes a pediatric indication for use in pediatric populations

aHUS = Atypical Hemolytic Uremic Syndrome; AS = Ankylosing Spondylitis; CD = Crohn’s Disease; CRS = Cytokine Release Syndrome; GCA = Giant Cell Arteritis; HS = Hidradenitis Suppurativa; MCD = Multicentric Castleman Disease; MG = Myasthenia Gravis; PFS = Periodic Fever Syndrome [Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal-Onset Multisystem Inflammatory Disease (NOMID)/Chronic Infantile Neurologic Cutaneous and Articular (CINCA) syndrome, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) and Familial Mediterranean Fever (FMF)]; PJIA = Polyarticular Juvenile Idiopathic Arthritis; PNH = Paroxysmal Nocturnal Hemoglobinuria; Ps = Plaque Psoriasis; PsA = Psoriatic Arthritis; RA = Rheumatoid Arthritis; SJIA = Systemic Juvenile Idiopathic Arthritis; UC = Ulcerative Colitis; UV = Uveitis.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

C9029

Injection, guselkumab, 1 mg [Tremfya]

J0129

Injection, abatacept, 10 mg [Orencia]

J0135

Injection, adalimumab, 20 mg [Humira]

J0638

Injection, canakinumab, 1 mg [Ilaris]

J0717

Injection, certolizumab pegol, 1 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self administered) [Cimzia]

J1300

Injection, eculizumab, 10 mg [Soliris]

J1438

Injection, etanercept; 25 mg (when drug administered under the direct supervision of a physician, not for use when drug is self administered) [Enbrel]

J1602

Injection, golimumab, 1 mg, for intravenous use [Simponi Aria]

J1745

Injection, infliximab, excludes biosimilar, 10 mg [Remicade]

J2793

Injection, rilonacept, 1 mg [Arcalyst]

J3262

Injection, tocilizumab, 1 mg [Actemra]

J3357

Ustekinumab, for subcutaneous injection, 1 mg [Stelara subcutaneous]

J3358

Ustekinumab, for intravenous injection, 1 mg [Stelara IV]

J3380

Injection, vedolizumab, 1 mg [Entyvio]

J3590

Unclassified biologics [no specific code for golimumab (Simponi), etanercept-szzs (Erelzi), adalimumab-atto (Amjevita), brodalumab (Siliq), ixekizumab (Taltz), secukinumab (Cosentyx), sarilumab (Kevzara), guselkumab (Tremfya), tildrakizumab-asmn (Ilumya)]

Q5103

Injection, infliximab-dyyb, biosimilar, (Inflectra), 10 mg

Q5104

Injection, infliximab-abda, biosimilar, (Renflexis), 10 mg

Discussion/General Information

TIMs are a category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis.  The first drug in this class was approved by the U.S. Food and Drug Administration (FDA) in 1998.  The approval of this drug, infliximab (Remicade), has subsequently been followed by numerous other drug approvals.

TIMs work by selectively blocking mechanisms involved in the inflammatory and immune response.  For example, one type of TIM known as “tumor necrosis factor inhibitors” functions by specifically blocking the action of proinflammatory mediators known as cytokines.  Others act by interfering with the function of lymphocytes.

Use of TIMs has become widespread, given their demonstrated safety and efficacy in multiple well-done studies published in the peer-reviewed medical literature.

References

Peer Reviewed Publications:

  1. Eguale T, Buckeridge DL, Verma A, et al. Association of off-label drug use and adverse drug events in an adult population. JAMA Intern Med. 2016; 176(1):55-63.
  2. Good CB, Gellad WF. Off-label drug use and adverse drug events: turning up the heat on off-label prescribing. JAMA Intern Med. 2016; 176(1):63-64.
  3. Smithburger PL, Buckley MS, Culver MA, et al. A multicenter evaluation of off-label medication use and associated adverse drug reactions in adult medical ICUs. Crit Care Med. 2015; 43(8):1612-1621.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Actemra [Product Information], South San Francisco, CA. Genentech Inc., Roche USA; Updated March 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125276s116,125472s030lbl.pdf. Accessed on April 4, 2018.
  2. American Hospital Formulary Service® (AHFS). AHFS Drug Information 2018®. Bethesda, MD: American Society of Health-System Pharmacists®; 2018.
  3. Arcalyst [Product Information], Tarrytown, NY. Regeneron Pharmaceuticals, Inc.; Updated September 2016. Available at: https://www.regeneron.com/sites/default/files/Arcalyst_FPI.pdf. Accessed on April 4, 2018.
  4. Cimzia [Product Information], Smyrna, GA. UCB, Inc.; Updated March 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125160s281lbl.pdf. Accessed on April 4, 2018.
  5. Cosentyx [Product Information], East Hanover, NJ. Novartis Pharmaceuticals Corporation; Updated January 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125504s013lbl.pdf. Accessed on April 4, 2018.
  6. DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated periodically. For additional information, visit the DrugPoints System website at: http://www.micromedexsolutions.com. Accessed on April 4, 2018.
  7. Enbrel [Product Information], Thousand Oaks, CA. Amgen Inc., Immunex Corporation; Updated October 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103795s5561lbl.pdf. Accessed on April 4, 2018.
  8. Entyvio [Product Information], Deerfield, IL. Takeda Pharmaceuticals America, Inc.; Updated February 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125476s022lbl.pdf. Accessed on April 4, 2018.
  9. Humira [Product Information], North Chicago, IL. Abbott Laboratories; Updated December 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125057s403lbl.pdf. Accessed on April 4, 2018.
  10. Ilaris [Product Information], East Hanover, NJ. Novartis Pharma Stein AG; Updated December 2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125319s088lbl.pdf. Accessed on April 4, 2018.
  11. Ilumya™ [Product Information], Whitehouse Station, NJ. Merck Sharp & Dohme Corp. and Merck & Co., Inc.; March 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761067s000lbl.pdf. Accessed on April 4, 2018.
  12. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 4, 2018.
  13. Orencia [Product Information], Princeton, NJ. Bristol-Myers Squibb Company; Updated June 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125118s209lbl.pdf. Accessed on April 4, 2018.
  14. Remicade [Product Information], Horsham, PA. Janssen Biotech Inc.; Updated October 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103772s5377lbl.pdf. Accessed on April 4, 2018.
  15. Siliq [Product Information], Bridgewater, NJ. Valeant Pharmaceuticals North America, LLC, Inc.; Updated on February 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf. Accessed on April 4, 2018.
  16. Simponi [Product Information], Horsham, PA. Janssen Biotech Inc.; Updated March 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125289s139lbl.pdf. Accessed on February 22, 2018.
  17. Simponi Aria [Product Information], Horsham, PA. Janssen Biotech Inc.; Updated February 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125433s024lbl.pdf. Accessed on April 4, 2018.
  18. Soliris [Product Information], New Haven, CT. Alexion Pharmaceuticals, Inc.; Updated February 28, 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125166s426lbl.pdf. Accessed on April 4, 2018.
  19. Stelara [Product Information], Horsham, PA. Janssen Biotech, Inc.; Updated February 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125261s141lbl.pdf. Accessed on April 4, 2018.
  20. Taltz [Product Information], Indianapolis, IN. Eli Lilly and Company; Updated December 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125521s004lbl.pdf. Accessed on April 4, 2018.
  21. Thaler KJ, Gartlehner G, Kien C, et al. Eds. Drug Class Review: Targeted Immune Modulators: Final Update 3 Report. Portland (OR): Oregon Health & Science University; 2012 Nov. Drug Class Reviews. Available at: https://www.ncbi.nlm.nih.gov/books/NBK110098/. Accessed on April 4, 2018.
  22. Tremfya [Product Information], Horsham, PA. Janssen Biotech Inc.; Updated July 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf. Accessed on April 4, 2018.
  23. U.S. Food and Drug Administration (FDA). Drugs@FDA Glossary of Terms. Label. Last updated November 14, 2017. Available at: http://www.fda.gov/drugs/informationondrugs/ucm079436.htm. Accessed on April 4, 2018.
  24. U.S. Food and Drug Administration (FDA). Orphan Drug Designations and Approvals. Available at: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm. Accessed on April 4, 2018.
Index

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Revised

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Added new drug approval for tildrakizumab-asmn (Ilumya) to document. Added Peer Reviewed Publications section to updated References section. Updated Description, Discussion, and Coding sections.

Revised

03/22/2018

MPTAC review. Added new criteria related to specific conditions and cost-effective agents. Added vedolizumab to document. Added new indication for ixekizumab and tocilizumab to document. Updated Description and References sections. Updated Coding section to include C9029, J3358 replacing Q9989, J3380, and 04/01/2018 HCPCS updates adding Q5103, Q5104 and removing Q5102 deleted 03/31/2018.

Revised

11/02/2017

MPTAC review. The document header wording updated from “Current Effective Date” to “Publish Date.” Removed vedolizumab from document. Replaced “preferred” with “cost-effective” in Clinically Equivalent Cost Effective Targeted Immune Modulators section. Updated Coding, Description and References sections.

New

08/03/2017

MPTAC review. Initial document development.