Medical Policy

Policy Num:      05.001.019
Policy Name:    ABATACEPT (ORENCIA)
Policy ID:          [05.001.019]  [Ac / L / M+ / P+]  [0.00.00]

Last Review:     October 24, 2024
Next Review:     October 20, 2025

Related Policies:  N/A

ABATACEPT (ORENCIA) 

Summary

From the decade of 1990 the advances in molecular biology have shown new approaches to the treatment for rheumatoid arthritis and after systemic inflammatory conditions associated to autoimmunity. The main approaches include agents that:

·         Interfere with the function of cytokines

·         Inhibit the "second signal" required for the activation of the T cells

·         Deplete the T cells

T (Th) cells secrete specific cytokines that in turn influence or perpetuate systemic inflammation.  Th cells and their cytokines can be divided in two subgroups, called Th1 and Th2.

The cytokines generated by Th1 or Th2 inhibit the cellular function of the other phenotype, for example, Interlukin 10, a cytokine segregated by Th2 inhibits the cellular function of Th1 and interferon gamma and Interlukin 12 produced by Th1 inhibit the proliferation of Th2 cells. Many of the biological therapies that have been developed aim to lower pro-inflammatory response of Th1 or increase the anti-inflammatory production of Th2 cytokine.

The Th1 lymphocytes participate in a wide variety of inflammatory processes such as rheumatoid arthritis, psoriasis, psoriatic arthritis, rejection of grafts, and others. The pro-inflammatory mediators produced by Th1cells include:

·         Interlukin (IL)-12

·         Interferon gamma

·         TNF

·         IL-15

·         IL-9

·         IL-10

·         Il-13

The Th2 lymphocytes stimulate the production of antibodies by the B cells and increase the eosinophilic response. Activation of Th2 cells contributes to the development of chronic rejection, systemic erythematosus lupus and systemic sclerosis. The mediators produced by Th2 cells include:

·         IL-4

·         IL-5

·         IL-9

·         IL-10

·         IL-13

The tumor necrosis factor (TNF) and Interleukin-1 beta (IL-1) are two cytokines that intervene in the pathogenesis of rheumatoid arthritis and other chronic inflammatory conditions. When they are secreted by the synovial macrophages, TNF and IL-1 stimulate the proliferation of the synovial cells and the production of collagenase inducing the degradation of the cartilage, the resorption of the bone and inhibits the repair of the cartilage.

TNF and IL_1 induce the molecular expression of cell adhesion resulting in intensification and release of additional cytokines such as IL-6, additional IL-1 and metabolites of arachidonic acid.

The TNF inhibitors have been approved by FDA for the treatment of some rheumatic diseases.

Abatacept (CTLA4-Ig) is a protein of soluble fusion that is formed by the Antigen 4 of the lymphocytes T and by the portion Fc of IgG1 that prevents or decreases the arthritis associated to the collagen.

Objective

The objective is to review the indications, contraindications and advers effects of the therapy with Orencia.

Policy Statements

 Abatacept is considered for payment in the following indications:

•          Adults with rheumatoid arthritis (RA) age 18 or older when the patient has had inadequate response after three months in treatment with any of the following:

 a.    Inhibitors of the tumor necrosis factor (etanercept, infliximab, adalimumab, antagonists of the receiver of Interleukin-1)

b.    Non biological Disease modifying anti-rheumatic drugs (DMARDs) (methotrexate, sulfasalazine, hydroxychloroquine, leflunomide).

• Moderate to severe Juvenile Idiopathic Arthritis (JIA) in children ≥ 2 years of age, as monotherapy or in combination with methotrexate
• Arthropathic psoriasis

• Active Psoriatic Arthritis (PsA)
• Rheumatoid lung disease with rheumatoid arthritis
• Rheumatoid arthritis with rheumatoid factor, unspecified

• Juvenile dermatopolymyositis:  Juvenile dermatomyositis, a rare but often severe and chronic systemic autoimmune disease, includes a large number of patients who are treatment resistant, requiring long term immunosuppressive therapy. A small open-label study published in Arthritis and Rheumatology shows promise using a targeted biologic therapy called abatacept to treat such patients. 
• Other and acute Pericarditis and Acute Myocarditis unspecified

Orencia may be considered investigational for all other ages and indications.

Policy Guidelines

Prior-Approval Requirements

Diagnoses

Patient must have ONE of the following:

1. Moderately to severely active rheumatoid arthritis (RA)

a. 18 years of age or older

b. Inadequate response, intolerance, or contraindication to a 3-month trial of at least ONE conventional disease-modifying antirheumatic drugs (DMARDs) (see Appendix 2)

c. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 60 kg – 500 mg every 4 weeks

ii. IV infusion: 60 kg to 100kg – 750 mg every 4 weeks

iii. IV infusion: More than 100 kg – 1000 mg every 4 weeks

iv. Subcutaneous administration: 125 mg every week

2. Active Juvenile Rheumatoid Arthritis (JRA)/ Polyarticular Juvenile Idiopathic Arthritis (pJIA)

a. 2 years of age or older

b. Inadequate response, intolerance, or contraindication to a 3-month trial of at least ONE conventional disease-modifying antirheumatic drugs (DMARDs) (see Appendix 2)

c. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 75kg – 10mg/kg every 4 weeks

ii. Subcutaneous administration: 10 to less than 25 kg – 50 mg every week

iii. Subcutaneous administration: 25 to less than 50 kg – 87.5 mg every week

iv. Subcutaneous administration: More than 50 kg – 125 mg every week

3. Active Psoriatic Arthritis (PsA)

a. 18 years of age or older

b. Inadequate response, intolerance or contraindication to a 3-month trial of at least ONE conventional DMARD (see Appendix 2)

c. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 60 kg – 500 mg every 4 weeks

ii. IV infusion: 60 kg to 100kg – 750 mg every 4 weeks

iii. IV infusion: More than 100 kg – 1000 mg every 4 weeks

iv. Subcutaneous administration: 125 mg every week

AND ALL of the following:

1. Tuberculin skin test conducted to rule out TB

a. Patients testing positive in tuberculosis screening must be treated by standard medical practice currently or completed prior to therapy.

2. Hepatitis B virus (HBV) has been ruled out or treatment initiated.

3. NO active infection

4. NOT to be used in combination with any other biologic DMARD or targeted synthetic DMARD (see Appendix 2)

5. NOT given concurrently with live vaccines

Prior – Approval Renewal Requirements

Diagnoses

Patient must have ONE of the following:

1. Rheumatoid Arthritis (RA) in adults

a. 18 years of age or older

b. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 60 kg – 500 mg every 4 weeks

ii. IV infusion: 60 kg to 100kg – 750 mg every 4 weeks

iii. IV infusion: More than 100 kg – 1000 mg every 4 weeks

iv. Subcutaneous administration: 125 mg every

2. Juvenile Rheumatoid Arthritis (JRA)/Polyarticular Juvenile Idiopathic Arthritis (pJIA)

a. 2 years of age or older

b. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 75kg – 10mg/kg every 4 weeks

ii. Subcutaneous administration: 10 to less than 25 kg – 50 mg every week

iii. Subcutaneous administration: 25 to less than 50 kg – 87.5 mg every week

iv. Subcutaneous administration: More than 50 kg – 125 mg every week

3. Psoriatic Arthritis (PsA)

a. 18 years of age or older

b. Prescriber will be dosing the patient within the FDA labeled maintenance dose of ONE of the following:

i. IV infusion: Less than 60 kg – 500 mg every 4 weeks

ii. IV infusion: 60 kg to 100kg – 750 mg every 4 weeks

iii. IV infusion: More than 100 kg – 1000 mg every 4 weeks

iv. Subcutaneous administration: 125 mg every week

AND ALL of the following:

1. Condition has improved or stabilized

2. Absence of active infection (including tuberculosis and hepatitis B virus (HBV))

3. NOT to be used in combination with any other biologic DMARD or targeted synthetic DMARD (see Appendix 1)

4. NOT given concurrently with live vaccines

Abatacept (Orencia)Oncologic Indications

Hematopoietic cell transplantation - in combination with a calcineurin inhibitor and methotrexate as prophylaxis of acute graft-versus-host disease (GVHD) in patients 2 years of age and older undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor

Intravenous Use for prophylaxis of aGVHD (2.4) (12/2021)

 For patients 6 years and older, administer at a 10 mg/kg dose (maximum dose 1,000 mg) as a 60-minute infusion on the day before transplantation, followed by a dose on Day 5, 14, and 28 after transplant (2.4).  For patients 2 to less than 6 years old, administer a 15 mg/kg dose as a 60-minute infusion on the day before transplantation, followed by a 12 mg/kg dose as a 60-minute infusion on Day 5, 14, and 28 after transplant .

Abatacept (Orencia) is recommended by the NCCN Drugs and Biologics Compendium^® for off-label use for the following indications:

• Hematopoietic cell transplantation - in combination with systemic corticosteroids for chronic GVHD as additional therapy following no response (steroid-refractory disease) to first-line therapy options
• Immunotherapy-related toxicities - as additional therapy for the management of suspected myocarditis if no improvement within 24 hours of starting pulse-dose methylprednisolone

Benefit Application

BlueCard/National Account Issues

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

 Orencia is a prescription medication that reduces signs and symptoms in adults with moderate to severe rheumatoid arthritis (RA), including those who have experienced an inadequate response to other medications for RA. Orencia may prevent further damage to bones and joints and may help the patient’s ability to perform daily activities. In adults, Orencia may be used alone or with other RA treatments other than tumor necrosis factor (TNF) antagonists (1).

Orencia is indicated to reduce the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in pediatric patients 2 years of age and older. Patients may receive Orencia alone (monotherapy) or in combination with methotrexate

Regulatory Status

FDA-approved indication: Orencia is a selective T cell co-stimulation modulator indicated for:

1. Adult Rheumatoid Arthritis (RA) – Moderately to severely active RA in adults. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists

2. Juvenile Idiopathic Arthritis – Moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 2 years of age and older. Orencia may be used as monotherapy or concomitantly with methotrexate

Rationale

Orencia is indicated for the treatment of moderately to severely active RA and PsA in adults, may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Orencia is also indicated for pediatric patients 2 years of age or older with moderately to severely active polyarticular juvenile idiopathic arthritis, may be used as monotherapy or concomitantly with methotrexate. Prior to initiating immunomodulatory therapies, including Orencia, patients should be screened for latent tuberculosis infection with a tuberculin skin test. Antirheumatic therapies have been associated with hepatitis B reactivation.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1

Individuals with Adult Rheumatoid arthritis and  

Individuals with Other and acute Pericarditis or Acute Myocarditis unspecified

Population Reference No. 2

Population Reference No. 3

Individuals with Juvenile Idiopathic Arthritis

Population Reference No. 4

Arthropathic psoriasis

Population Reference No. 5

Rheumatoid lung disease with rheumatoid arthritis

Population Reference No. 6 

Rheumatoid arthritis with rheumatoid factor, unspecified

Population Reference No. 7

Active Psoriatic Arthritis (PsA) in Adults and  pediatric patients 2 years of age and older. 

Indicated for the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA). Change on 10/2023 Orencia PI. Pediatric Patients Administer ORENCIA as a subcutaneous injection in pediatric patients 2 years of age and older with psoriatic arthritis [see Use in Specific Populations (8.4) in PI]. ORENCIA may be used as monotherapy or concomitantly with methotrexate. Intravenous administration is not approved for pediatric patients with psoriatic arthritis.

Population Reference No. 8

JIA uveitis

Population Reference No. 9

JIA systemic

Population Reference No. 10

• Hematopoietic cell transplantation - in combination with a calcineurin inhibitor and methotrexate as prophylaxis of acute graft-versus-host disease (GVHD) in patients 2 years of age and older undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor   FDA approved

Population Reference No. 11

NCCN Drugs and Biologics Compendium^® for off-label use   2A positioning

• Hematopoietic cell transplantation - in combination with systemic corticosteroids for chronic GVHD as additional therapy following no response (steroid-refractory disease) to first-line therapy options

Population Reference No. 12

NCCN Drugs and Biologics Compendium^® for off-label use   2A positioning

• Immunotherapy-related toxicities - as additional therapy for the management of suspected myocarditis if no improvement within 24 hours of starting pulse-dose methylprednisolone

Population Reference No. 13

Juvenile dermatopolymyositis

Supplemental Information

N/A

Practice Guidelines and Position Statements

N/A

Medicare National Coverage

N/A

References

1.    Lipsky, PE, Davis, LS. The central involvement of T cells in rheumatoid arthritis. The Immunologist 1998; 6:121.

2.    Kotzin BL, Kappler J. Targeting the T cell receptor in rheumatoid arthritis. Arthritis Rheum 1998; 41:1906.

3.    Orencia (abatacept) Indication and important safety information. Bistol-Meyers Squib Manufacturer's information 2006.

4.    Abatacept (Orencia) for rheumatoid arthritis. Med Lett Drugs Ther 2006; 48:17.

5.    Fernandez-Botran R Soluble cytokine receptors: their role in immunoregulation. FASEB J. 1991; 5 (11):2567.

6.    Bendtzen K, Hansen MB, Ross C, et. al. Cytokines and autoantibodies to cytokines. Stem Cells. 1995; 13 (3):206.

7.    Arend WP, Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest. 1991; 88 (5):1445.

8.    Heaney ML, Golde DW, Soluble cytokine receptors. Blood. 1996;87 (3):847.

9.    Arend WP, Interleukin-1 receptor antagonist. Adv Immunol. 1993; 54:167.

10.  Smith RJ, Chin JE, Sam LM, Justen JM. Biologic effects of an interleukin-1 receptor antagonist protein on interleukin-1-stimulated cartilage erosion and chondrocyte responsiveness. Arthritis Rheum. 1991;34 (1):78.

11. Doan T and Massarotti E, “Rheumatoid Arthritis: An Overview of New and Emerging Therapies,” J Clin Pharmacol, 2005, 45(7):751-62. [PubMed 15951465]

12. Furst DE, Breedveld FC, Kalden JR, et al, “Updated Consensus Statement on Biological Agents for the Treatment of Rheumatic Diseases, 2007,” Ann Rheum Dis, 2007, 66(Suppl 3):2-22. [PubMed 17934088]

13. Genovese MC, Becker JC, Schiff M, et al, “Abatacept for Rheumatoid Arthritis Refractory to Tumor Necrosis Factor Alpha Inhibition,” N Engl J Med, 2005, 353(11):1114-23. [PubMed 16162882]

14. Kremer JM, Dougados M, Emery P, et al, “Treatment of Rheumatoid Arthritis With the Selective Costimulation Modulator Abatacept: Twelve-Month Results of a Phase IIb, Double-Blind, Randomized, Placebo-Controlled Trial,” Arthritis Rheum, 2005, 52(8):2263-71. [PubMed 16052582]

15. Kremer JM, Genant HK, Moreland LW, et al, “Effects of Abatacept in Patients With Methotrexate-Resistant Active Rheumatoid Arthritis: A Randomized Trial,” Ann Intern Med, 2006, 144(12):865-76. [PubMed 16785475]

16. Kremer JM, Westhovens R, Leon M, et al, “Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation With Fusion Protein CTLA4Ig,” N Engl J Med, 2003, 349(20):1907-15. [PubMed 14614165]

17. Singh JA, Furst DE, Bharat A, et al, “2015 Update of the 2012 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), 2015, 64(5):625-39. [PubMed 22473917]

18. Tay L, Leon F, Vratsanos G, et al, “Vaccination Response to Tetanus Toxoid and 23-Valent Pneumococcal Vaccines Following Administration of a Single Dose of Abatacept: A Randomized, Open-Label, Parallel Group Study in Healthy Subjects,” Arthritis Res Ther, 2007, 9(2): R38. [PubMed 17425783]

19. Weinblatt M, Combe B, Covucci A, et al, “Safety of the Selective Costimulation Modulator Abatacept in Rheumatoid Arthritis Patients Receiving Background Biologic and Nonbiologic Disease-Modifying Antirheumatic Drugs: A One-Year Randomized, Placebo-Controlled Study,” Arthritis Rheum, 2006, 54(9):2807-16. [PubMed 16947384]

20. Orencia [package insert]. Princeton, NJ: Bristol-Myers Squibb; June 2017.

        21.  Ringold S, Weiss P, et.al. 2013 Update of the 2011 American College of Rheumatology                   Recommendations for the
             Treatment of Juvenile Idiopathic Arthritis. Arthritis Care & Rheumatism. 2013;65(10): 2499-               2512

         22.  First Coast Service Options, Inc. Local Coverage Determination (LCD): Abatacept (L33257) . Centers for Medicare &  Medicaid Services, Inc. Updated on 12/11/2017 with effective date 1/02/2018. Accessed May 2018. Retired LCD. 

         23.  Bristol-Myers Squibb. Orencia (abatacept) prescribing information. Princeton NJ: Bristol-Myers Squibb; 2020. Available from:                                                                  http://packageinserts.bms.com/pi/pi_orencia.pdf [Rev 6/2020].

24.   Bristol-Myers Squibb Company, Orencia (abatacept) prescribing information. Rev 12/2021

25. Orencia: NCCN Content © National Comprehensive Cancer Network, Inc 2011-2022

26.  “Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy,” was published online in Arthritis and Rheumatology.

27. Orencia: NCCN Content © National Comprehensive Cancer Network, Inc 2011-2023

28. Orencia (Abatacept) PI change 10/2023 Section 1.3 and 2.3 Pediatric Patiens.

Codes

Codes	Numbers	Description
HCPCS	J0129	Injection, abatacept, 10 mg
ICD-10-CM (effective 10/1/15)	M06.811-M06.89	Other specified rheumatoid arthritis code range
	M06.00-M06.09	Rheumatoid arthritis without rheumatoid factor
	M08.00-M08.99	Juvenile rheumatoid arthritis (code range)
	L40.50-L40.59	Arthropathic psoriasis
	M05.10-M05.89	Rheumatoid lung disease with rheumatoid arthritis
	M05.9	Rheumatoid arthritis with rheumatoid factor, unspecified
	D89.81-D89.813	Graft-versus-host disease
	I40.0-I40.9	Myocarditis
	M33.90-M33.99	Juvenile dermatopolymyositis
	T86.09	Other complications of bone marrow transplant
	I30.8, I30.9	Other and acute pericarditis

Applicable Modifiers

As per correct coding guidelines

Policy History