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Abatacept (Orencia®) for Injection for Intravenous Use
MA08.028g

Policy

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

​HEMATOPOIETIC CELL TRANSPLANTATION  
Prophylaxis of Acute Graft-Versus-Host Disease (aGVHD) 

Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered for the prophylaxis of acute graft-versus-host disease (aGVHD), in combination with a calcineurin inhibitor (e.g., cyclosporine, tacrolimus) and methotrexate when all of the following inclusion criteria are met: 
  • ​The individual is undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
  • Active or latent tuberculosis (TB) has been ruled out.
  • The individual is two years of age or older.
  • Abatacept (Orencia) will not be used in combination with other biologic DMARDs (e.g., tumor necrosis factor [TNF] antagonistsor Janus kinase (JAK) ​inhibitors (e.g. baricitinib, tofacitinib, upadacitinib).
Treatment of Chronic Graft-Versus-Host Disease (GVHD)  

Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered for the treatment of chronic graft-versus-host disease (GVHD) as additional therapy in conjunction with systemic corticosteroids following no response (steroid-refractory disease) to first-line therapy options

IMMUNE CHECKPOINT INHIBITOR-RELATED TOXICITIES 
Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered as additional therapy for the management of the following immune checkpoint inhibitor-related autoimmune-like toxicity (also known as immune-related adverse event): myocarditis, if no improvement within 24​-48 hours of starting pulse-dose methylprednisolone​

POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS
Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered when used in individuals who have moderately to severely active polyarticular juvenile idiopathic arthritis. Abatacept (Orencia) injection for intravenous use may be covered as monotherapy or concomitantly with methotrexate when all of the following inclusion criteria are met:
  • Active or latent tuberculosis (TB) have been ruled out.
  • The individual has had an inadequate response after at least three months of one or more disease-modifying antirheumatic drugs (DMARDs), or the use of all DMARDs is contraindicated in the individual.
  • The individual is six years of age or older.
  • Abatacept (Orencia) will not be used in combination with other biologic DMARDs  or JAK ​inhibitors.
PSORIATIC ARTHRITIS (PsA)
Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered for the treatment of active psoriatic arthritis. Abatacept (Orencia) injection for intravenous use may be covered as monotherapy or concomitantly with non-biologic DMARDs when all of the following inclusion criteria are met:
  • Active or latent tuberculosis (TB) have been ruled out.
  • The individual has had an inadequate response after at least three months of one or more DMARDs, or the use of all DMARDs is contraindicated in the individual.
  • The individual is 18 years of age or older.
  • Abatacept (Orencia) will not be used in combination with other biologic DMARDs or JAK ​inhibitors.
RHEUMATOID ARTHRITIS (RA)
Abatacept (Orencia) injection for intravenous use is considered medically necessary and, therefore, covered in individuals who have moderately to severely active RA. Abatacept (Orencia) injection for intravenous use may be covered as monotherapy or concomitantly with DMARDs, other than JAK ​inhibitors or biologic DMARDs, when all of the following inclusion criteria are met:
  • Active or latent tuberculosis (TB) have been ruled out.
  • The individual has had an inadequate response after at least three months to one or more DMARDs or tumor necrosis factor (TNF) antagonists, or the use of all DMARDs or TNF-antagonists is contraindicated in the individual.
  • The individual is 18 years of age or older.
  • Abatacept (Orencia) will not be used in combination with other biologic DMARDs or JAK ​inhibitors.​
EXPERIMENTAL/INVESTIGATIONAL

All other uses for abatacept (Orencia) injection for intravenous use 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. Uses of abatacept (Orencia) injection for intravenous uses that are not supported in either this medical policy or the off-label coverage policy are considered experimental/investigational and, therefore, not covered.

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

This policy is consistent with Medicare’s coverage determination. The Company’s payment methodology may differ from Medicare.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, abatacept (Orencia) injection for intravenous use is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when abatacept (Orencia) injection for intravenous use is covered under a member's medical benefit. It does not address instances when abatacept (Orencia) injection for intravenous use is covered under a member’s pharmacy benefit.

Abatacept (Orencia) injection for subcutaneous use is not covered under the medical benefits for most of the Company’s products. Abatacept (Orencia) injection for subcutaneous use may be covered under a member’s pharmacy benefit, if applicable.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Initial FDA approval for abatacept (Orencia) injection for intravenous use was granted on December 23, 2005. Supplemental approvals for abatacept (Orencia) injection for intravenous use have since been issued. Abatacept (Orencia) injection for subcutaneous use was approved by the FDA on July 29, 2011.

A single loading dose infusion of abatacept (Orencia) injection for intravenous use may be given to an individual who will receive subcutaneous abatacept (Orenciafor treatment of adult rheumatoid arthritis.

PEDIATRIC USE
For pediatric juvenile idiopathic arthritis, the safety and effectiveness of abatacept (Orencia) injection for intravenous use in pediatric individuals younger than six years of age have not been established. Therefore, abatacept (Orencia) injection for intravenous use ​in pJIA is not recommended for use in individuals younger than six years of age.

For 
the prophylaxis of acute graft versus host disease (aGVHD), the safety and effectiveness of abatacept (Orencia) injection for intravenous use in pediatric individuals younger than two years of age have not been established. Therefore, abatacept (Orencia) injection for intravenous use ​in aGVHD is not recommended for use in individuals younger than two years of age.


DRUG INTERACTIONS
Concurrent administration of a TNF antagonist (e.g., adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi, Simponi Aria], infliximab [Remicade]) with abatacept (Orencia) injection for intravenous use has been associated with an increased risk of serious infections and no significant additional efficacy over use of the TNF-antagonists alone. Concurrent therapy with abatacept (Orencia) injection for intravenous use and TNF-antagonists is not recommended.

​There is insufficient experience to assess the safety and efficacy of abatacept (Orencia)​ administered concurrently with other biologic RA therapy, such as anakinra (Kineret), or other biologic RA/PsA therapy, and JAK inhibitors. Therefore, such use is not recommended.

Description

Abatacept (Orencia) injection for intravenous use is a soluble fusion protein that is produced by recombinant deoxyribonucleic acid (DNA) technology. It is a selective costimulation modulator that consists of human cytotoxic T-lymphocyte-associated antigen-4 linked to a modified portion of human immunoglobulin G1 (IgG1).

The activation of T lymphocytes has been implicated in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Because abatacept (Orencia) injection for intravenous use interrupts T lymphocyte activation, it has been studied to be effective for the treatment of RApolyarticular juvenile idiopathic arthritis​ (pJIA), and PsA, and is frequently used in the management of adults and children with polyarticular juvenile idiopathic arthritis (PJIA).

The American College of Rheumatology's (ACR) guidelines for the treatment of RA recommend that newly diagnosed individuals with RA begin treatment with disease-modifying antirheumatic drugs (DMARDs). DMARDs act to slow down disease progression, and some act with mild chemotherapeutic action, causing immunosuppression. The ACR Guidelines for the treatment of PJIA recommend NSAIDs or DMARDs as initial therapy. Although there are no ACR Guidelines for PsA, initial treatment typically includes NSAIDs or DMARDs.

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, infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), anakinra (Kineret), golimumab (Simponi, Simponi Aria), tocilizumab (Actemra), and rituximab (Rituxan).

Abatacept (Orencia) is available in two forms: injection for intravenous use and injection for subcutaneous use.

PEER-REVIEWED LITERATURE

SUMMARY
Acute Graft versus Host Disease (aGVHD), Prophylaxis

The safety and efficacy of abatacept (Orencia) injection for intravenous use, in combination with a calcineurin inhibitor (CNI) (e.g., cyclosporine, tacrolimus)​ and methotrexate (MTX),​ for the prophylaxis of aGVHD was accessed in two clinical studies. 

The first was a Phase II, double-blind, multicenter, two cohort clinical study (GVHD-1) in individuals 6 years of age and older who underwent hematopoietic stem cell transplantation (HSCT) from a matched or 1 allelemismatched unrelated donor. The two cohorts in GVHD-1 included: 
  1. an open-label, single-arm study of 43 individuals who underwent a 7 of 8 Human Leukocyte Antigen (HLA)-matched HSCT (7 of 8 cohort)
  2. a randomized (1:1), double-blind, placebo-controlled study of 142 individuals ​who underwent an 8 of 8 HLA-matched HSCT who received abatacept (Orencia) or placebo in combination with a CNI and MTX (8 of 8 cohort). 
In both cohorts, individuals in the abatacept (Orencia) group received 10 mg/kg (1000 mg maximum dose) IV over 60 minutes on the day before transplantation (Day -1), followed by administration on Days 5, 14, and 28 after transplantation. In cohort 1, an exploratory analysis revealed the following rates of grade III to IV GFS (95%), grade II to IV GFS (53%), and overall survival (98%) at day 180 post transplantation.​ In cohort 2, at Day 180 post-transplantation, there was significantly improved overall survival (OS) rate in the abatacept (Orencia) + CNI + MTX group​ of 97% compared to 84% for the placebo group. There was also a significantly improved rate of aGVHD-free survival (GFS)​ for moderate-severe (grade II-IV) aGVHD in the abatacept (Orencia) + CNI + MTX​ group​ (50%), compared to the placebo group (32%). However, severe (grade III-IV)​ aGVHD-free survival (GFS) was not significantly improved in the abatacept (Orencia) group ​(87%) compared to those who received a placebo (75%). 
​The second clinical study, GVHD-2, used real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR). The study analyzed the outcomes of individuals 6 years of age or older who underwent HSCT from a 1 allele-mismatched URD between 2011 and 2018 and received ​abatacept (Orencia) in combination with a CNI and MTX, versus a CNI + MTX alone, for the prophylaxis of aGVHDThe abatacept (Orencia)​ + CNI + MTX group (n=54) included 42 individuals ​from the GVHD-1 study, in addition to 12 individuals treated with abatacept (Orencia) outside of GVHD-1. The comparator group (n=162) received CNI + MTX alone, and were randomly selected in a 3:1 ratio to the abatacept (Orencia) + CNI + MTX group from the CIBMTR registry from individuals​. The study measured overall survival (OS) six months after transplantation. Those in the abatacept (Orencia) + CNI + MTX group​ saw a 98% overall survival rate compared to 75% for those who received CNI + MTX alone​.

The most common side effects of abatacept (Orencia) ​for prevention of aGVHD included anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleed, decreased levels of specific white blood cells called CD4 lymphocytes, increased levels of magnesium in the blood and acute kidney injury.

Polyarticular Juvenile Idiopathic Arthritis

The safety and efficacy of abatacept (Orencia) injection for intravenous use in the treatment of juvenile idiopathic arthritis was assessed in a three-part study with individuals ages six years to 17 years with moderate to severely active polyarticular juvenile idiopathic arthritis with inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDS). The principal measure of clinical response in part A of this study was the American College of Rheumatology (ACR) pediatric 30 definition of improvement (i.e., 30% or greater improvement in at least 3 of 6 and 30% or greater deterioration in no more than 1 of 6 core set criteria that include physician and child/parent global assessments, active joint count, limitation of motion, functional assessment, and erythrocyte sedimentation rate). Individuals with an "ACR pediatric 30" response at the end of part A were randomized into part B, the double blind phase. In part B, the primary endpoint was time to disease flare (defined as a 30% or greater deterioration in 3 of 6 and a 30% or greater improvement in no more than 1 of 6 core set criteria). At the end of part B, study participants treated with abatacept (Orencia) injection for intravenous use reported significantly fewer disease flares as compared to individuals treated with placebo. (Part C of the study was an open label extension.)

At the conclusion of part A, pediatric ACR 30/50/70 responses were 65 percent, 50 percent, and 28 percent, respectively. During part B, study participants reported significantly fewer disease flares compared to placebo-treated study participants. Among study participants who received abatacept (Orencia) injection for intravenous use throughout the study period (part A, B and C), the proportion of pediatric ACR 30/50/70 responders remained consistent for one year.

Psoriatic Arthritis

The safety and efficacy of abatacept (Orencia) injection for intravenous use was assessed in a Phase II, randomized, double-blind, multi-center, dose-ranging study of 170 adults with active arthritis (defined as the presence of 3 or more swollen joints and 3 or more tender joints), and active plaque psoriasis (with at least 1 qualifying target lesion of 2 cm or more in diameter). Participants had an inadequate response to DMARDs, including, but not limited to, MTX or anti-TNF agents. Participants were randomized (1:1:1:1) to receive placebo or abatacept (Orencia) IV infusions at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter for six months. The primary end point of this study was ACR 20 response on day 169, resulting in 42% in those who received 30/10 mg/kg of abatacept (Orencia), 48% who received 10 mg/kg, 33% who received 3 mg/kg, and 19% who received placebo. Compared to placebo, the ACR20 responses were statistically significant for the 30/10 mg/kg (P = 0.022) and the 10 mg/kg (P= 0.006), but not the 3 mg/kg (P= 0.121), doses of abatacept (Orencia).

Genovese 2011, et al performed a non-inferiority study in the treatment of RA showing the therapeutic equivalence of abatacept (Orencia) dosing at 10 mg/kg IV every 4 weeks and 125 mg subcutaneously (SC) weekly. Furthermore, the safety and efficacy of abatacept (Orencia) 125 mg weekly SC injection was performed in a randomized, double-blind, Phase III study in the treatment of 424 adults with active psoriatic arthritis (as defined in previous study). Participants had an inadequate response or intolerance to one or more DMARDs, including, but not limited to, MTX or anti-TNF agents. Participants were randomized (1:1) to receive placebo or abatacept (Orencia) subcutaneous 125 mg weekly for 24 weeks followed by open-label subcutaneous abatacept. As the primary endpoint, abatacept (Orencia) significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001).

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 College of Rheumatology. Juvenile Arthritis. [American College of Rheumatology Web site]. 12/2021. Available at: http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/juvenilearthritis.asp. Accessed April 7, 2022.

American Hospital Formulary Service (AHFS). Drug Information 2022. Orencia (abatacept). [Lexicomp Online Web site]. 02/01/2021. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed April 7, 2022.

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.  

Elsevier’s Clinical Pharmacology Compendium. Abatacept (Orencia®). 12/21/2021. [Clinical Pharmacology Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed April 7, 2022.

Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021 Jul;73(7):924-939.

Lexi-Drugs CompendiumAbatacept (Orencia®). 03/18/2022. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed April 7, 2022.

Genovese MC, Covarrubias A, Leon G, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum. 2011 Oct;63(10):2854-64.

Mease P, Genovese M, Gladstein G, et al. Abatacept in the treatment of patients with psoriatic arthritis: Results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. Arthritis & Rheumatism. 2011; 63(4): 939 – 948.

Mease PJ, Gottlieb A, van der Heijde D, et al. Efficacy and safety of abatacept, a T-cell modulator in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis. Ann Rheum Dis. 2017 Sep;76(9):1550-1558.

Nahas MR, Soiffer RJ, Kim HT, et al. Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Blood. 2018 Jun 21;131(25):2836-2845. 

National Comprehensive Cancer Network (NCCN).  NCCN Clinical Practice Guidelines in Oncology - Hematopoeitic Cell Transplantation (HCT). V.1.2022. 04/01/2022. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf [via free subscription]. Accessed April 6, 2022.

National Comprehensive Cancer Network (NCCN).  NCCN Clinical Practice Guidelines in Oncology - Management of Immunotherapy-related Toxicities. V.1.2022. 02/28/2022. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf ​ [via free subscription]. Accessed ​April 6, 2022.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Abatacept. [NCCN Web site]. 2022. Available at: ​https://www.nccn.org/professionals/drug_compendium/content/. Accessed April 6, 2022.

Novitas Solutions, Inc. Article (A53127) For Self-Administered Drug Exclusion List. [Novitas Medicare Services Web site]. Original: 10/​01/2015, Revised: 10/21/2021. Available at: https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleid=53127&ver=97&keyword=orencia&keywordType=starts&areaId=s45&docType=NCA,CAL,NCD,MEDCAC,TA,MCD,6,3,5,1,F,P&contractOption=all&sortBy=relevance&bc=1 . Accessed April 7, 2022.

Orencia® (abatacept) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 12/2021. Available at: http://packageinserts.bms.com/pi/pi_orencia.pdfAccessed April 6, 2022.

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, Weis PF, Beukelman T, et al. 2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis. Arthritis Rheum. 2013;65(10):2499-2512.

Singh JA, Guyatt G, Ogdie A, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019;71(1):5-32.

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 Jan;68(1):1-26. Review.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Orencia® (abatacept). 01/14/2022Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 7, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Abatacept (Orencia®) [prescribing information]. [FDA Web site]. 12/15/2021. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed April 6, 2022.​

Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
See Attachment A for ICD-10 codes.

HCPCS Level II Code Number(s)
J0129 Injection, abatacept, 10 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)

Revenue Code Number(s)
N/A

Modifiers

THE FOLLOWING MODIFIER IS USED WHEN REPORTING ABATACEPT (ORENCIA) FOR INJECTION FOR INTRAVENOUS USE:

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.

Policy History

6/6/2022
6/6/2022
MA08.028
Medical Policy Bulletin
Medicare Advantage
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No