Subject: Enbrel 2003-A SGM P2020a
Policy:
I. INDICATIONS
The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all
the approval criteria are met and the member has no exclusions to the prescribed therapy.
A. FDA-Approved Indications
1. Moderately to severely active rheumatoid arthritis (RA)
2. Moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA) in patients aged 2 years or older
3. Active psoriatic arthritis (PsA)
4. Active ankylosing spondylitis (AS)
5. Chronic moderate to severe plaque psoriasis (PsO) in patients aged 4 years or older
B. Compendial Uses
1. Axial spondyloarthritis
2. Oligoarticular juvenile idiopathic arthritis
3. Reactive arthritis
4. Hidradenitis suppurativa, severe, refractory
5. Behcet’s disease
6. Graft versus host disease
7. Pyoderma gangrenosum, refractory
All other indications are considered experimental/investigational and not medically necessary.
II. DOCUMENTATION
Submission of the following information is necessary to initiate the prior authorization review:
A. Rheumatoid arthritis (RA)
1. For initial requests:
i. Chart notes, medical record documentation, or claims history supporting previous medications tried (if applicable),
including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy.
ii. Laboratory results, chart notes, or medical record documentation of biomarker testing (i.e., rheumatoid factor [RF], anti-
cyclic citrullinated peptide [anti-CCP], and C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR]) (if
applicable).
2. For continuation requests: Chart notes or medical record documentation supporting positive clinical response.
B. Articular juvenile idiopathic arthritis, ankylosing spondylitis (AS), active axial spondyloarthritis, and reactive arthritis:
1. Initial requests: Chart notes, medical record documentation, or claims history supporting previous medications tried (if
applicable), including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy.
2. Continuation requests: Chart notes or medical record documentation supporting positive clinical response.
C. Psoriatic arthritis (PsA): For continuation requests: Chart notes or medical record documentation supporting positive clinical
response.
D. Plaque psoriasis
1. Initial requests:
i. Chart notes or medical record documentation of affected area(s) and body surface area (BSA) affected.
ii. Chart notes, medical record documentation, or claims history supporting previous medications tried (if applicable),
including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy.
2. Continuation requests: Chart notes or medical record documentation of decreased body surface area (BSA) affected and/or
improvement in signs and symptoms
E. Hidradenitis suppurativa
1. Initial requests: Chart notes, medical record documentation, or claims history supporting previous medications tried (if
applicable), including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy.
2. Continuation requests: Chart notes or medical record documentation supporting positive clinical response to therapy.
F. Graft versus host disease and pyoderma gangrenosum (initial requests only): Chart notes, medical record documentation, or
claims history supporting previous medications tried (if applicable), including response to therapy. If therapy is not advisable,
documentation of clinical reason to avoid therapy.
G. Behcet’s disease (initial requests only): Chart notes, medical record documentation, or claims history supporting previous
medications tried, including response to therapy (if applicable).
III. CRITERIA FOR INITIAL APPROVAL
A. Moderately to severely active rheumatoid arthritis (RA)
1. Authorization of 12 months may be granted for members who have previously received a biologic or targeted synthetic
DMARD (e.g., Rinvoq, Xeljanz) indicated for moderately to severely active rheumatoid arthritis.
2. Authorization of 12 months may be granted for treatment of moderately to severely active RA when all of the following
criteria are met:
i. Member meets either of the following criteria:
a. Member has been tested for either of the following biomarkers and the test was positive:
1. Rheumatoid Factor (RF)
2. Anti-cyclic citrullinated peptide (anti-CCP)
b. Member has been tested for ALL of the following biomarkers:
1. RF
2. Anti-CCP
3. C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR)
ii. Member meets either of the following criteria:
a. Member has experienced an inadequate response to at least a 3-month trial of methotrexate despite adequate dosing
(i.e., titrated to 20 mg/week).
b. Member has an intolerance or contraindication to methotrexate (see Appendix A)
B. Moderately to severely active articular juvenile idiopathic arthritis
1. Authorization of 12 months may be granted for members who have previously received a biologic or targeted synthetic DMARD indicated for moderately to severely active articular juvenile idiopathic arthritis.
2. Authorization of 12 months may be granted for the treatment of moderately to severely active articular juvenile idiopathic arthritis when any of the following criteria are met:
i. The member has had an inadequate response to methotrexate or another non-biologic DMARD administered at an adequate dose and duration.
ii. The member has risk factors (See Appendix C) and the member also meets one of the following:
a. High-risk joints are involved (e.g., cervical spine, wrist, or hip).
b. High disease activity.
c. Are judged to be at high risk for disabling joint disease.
C. Active psoriatic arthritis (PsA)
Authorization of 12 months may be granted for treatment of active psoriatic arthritis (PsA).
D. Active ankylosing spondylitis (AS) and active axial spondyloarthritis
1. Authorization of 12 months may be granted for members who have previously received a biologic indicated for active ankylosing spondylitis or active axial spondyloarthritis.
2. Authorization of 12 months may be granted for treatment of active ankylosing spondylitis or active axial spondyloarthritis when any of the following criteria is met:
i. Member has experienced an inadequate response to at least two non-steroidal anti-inflammatory drugs (NSAIDs).
ii. Member has an intolerance or contraindication to two or more NSAIDs.
E. Moderate to severe plaque psoriasis
1. Authorization of 12 months may be granted for members who have previously received Otezla or a biologic indicated for the treatment of moderate to severe plaque psoriasis.
2. Authorization of 12 months may be granted for treatment of moderate to severe plaque psoriasis in members when any of the following criteria is met:
i. Crucial body areas (e.g., hands, feet, face, neck, scalp, genitals/groin, intertriginous areas) are affected.
ii. At least 10% of the body surface area (BSA) is affected
iii. At least 3% of body surface area (BSA) is affected and the member meets any of the following criteria:
a. Member has had an inadequate response or intolerance to either phototherapy (e.g., UVB, PUVA) or pharmacologic treatment with methotrexate, cyclosporine, or acitretin.
b. Member has a clinical reason to avoid pharmacologic treatment with methotrexate, cyclosporine, and acitretin (see Appendix B).
F. Reactive arthritis
1. Authorization of 12 months may be granted for members who have previously received a biologic indicated for reactive arthritis.
2. Authorization of 12 months may be granted for treatment of reactive arthritis when any of the following criteria is met:
i. Member has experienced an inadequate response to at least a 3-month trial of methotrexate despite adequate dosing (i.e., titrated to 20 mg/week).
ii. Member has an intolerance or contraindication to methotrexate (see Appendix A).
G. Hidradenitis suppurativa
1. Authorization of 12 months may be granted for members who have previously received a biologic indicated for the treatment of severe, refractory hidradenitis suppurativa.
2. Authorization of 12 months may be granted for treatment of severe, refractory hidradenitis suppurativa when either of the following is met:
i. Member has experienced an inadequate response to oral antibiotics for at least 90 days.
ii. Member has an intolerance or contraindication to oral antibiotics.
H. Graft versus host disease
Authorization of 12 months may be granted for treatment of graft versus host disease when either of the following criteria is met:
1. Member has experienced an inadequate response to systemic corticosteroids.
2. Member has an intolerance or contraindication to corticosteroids.
I. Behcet’s disease
1. Authorization of 12 months may be granted for members who have previously received Otezla or a biologic indicated for the treatment of Behcet’s disease.
2. Authorization of 12 months may be granted for the treatment of Behcet’s disease when the member has had an inadequate response to at least one nonbiologic medication for Behcet’s disease (e.g., apremilast, colchicine, systemic glucocorticoids, azathioprine)
J. Pyoderma gangrenosum
1. Authorization of 12 months may be granted for members who have previously received a biologic indicated for treatment of
pyoderma gangrenosum.
2. Authorization of 12 months may be granted for treatment of pyoderma gangrenosum when either of the following is met:
i. Member has experienced an inadequate response to corticosteroids or immunosuppressive therapy (e.g., cyclosporine or
mycophenolate mofetil).
ii. Member has an intolerance or contraindication to corticosteroids and immunosuppressive therapy (e.g., cyclosporine,
mycophenolate mofetil).
IV. CONTINUATION OF THERAPY
A. Moderately to severely active rheumatoid arthritis (RA)
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for moderately to severely active rheumatoid arthritis and who achieve or maintain a positive clinical response as evidenced by
disease activity improvement of at least 20% from baseline in tender joint count, swollen joint count, pain, or disability.
B. Moderately to severely active articular juvenile idiopathic arthritis
Authorization of 12 months may be granted for all members (including new members) who are using the requested
medication for moderately to severely active articular juvenile idiopathic arthritis and who achieve or maintain a positive
clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is
improvement in any of the following from baseline:
1. Number of joints with active arthritis (e.g., swelling, pain, limitation of motion)
2. Number of joints with limitation of movement
3. Functional ability
C. Active psoriatic arthritis
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for active psoriatic arthritis and who achieve or maintain a positive clinical response as evidenced by low disease activity or
improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:
1. Number of swollen joints
2. Number of tender joints
3. Dactylitis
4. Enthesitis
5. Skin and/or nail involvement
D. Active ankylosing spondylitis (AS) and active axial spondylarthritis
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for active ankylosing spondylitis or active axial spondyloarthritis and who achieve or maintain a positive clinical response with
the requested medication as evidenced by low disease activity or improvement in signs and symptoms of the condition when
there is improvement in any of the following from baseline:
1. Functional status
2. Total spinal pain
3. Inflammation (e.g. morning stiffness)
E. Moderate to severe plaque psoriasis
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for moderate to severe plaque psoriasis and who achieve or maintain positive clinical response as evidenced by low disease
activity or improvement in signs and symptoms of the condition when any of the following is met:
1. Reduction in body surface area (BSA) affected from baseline
2. Improvement in signs and symptoms from baseline (e.g., itching, redness, flaking, scaling, burning, cracking, pain)
F. Reactive arthritis
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for reactive arthritis and who achieve or maintain a positive clinical response as evidenced by low disease activity or
improvement in signs and symptoms of the condition (e.g., tender joint count, swollen joint count, or pain).
G. Hidradenitis suppurativa
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication
for severe, refractory hidradenitis suppurativa and who achieve or maintain a positive clinical response as evidenced by low
disease activity or improvement in signs and symptoms of the condition when any of the following is met:
1. Reduction in abscess and inflammatory nodule count from baseline
2. Reduced formation of new sinus tracts and scarring
3. Decrease in frequency of inflammatory lesions from baseline
4. Reduction in pain from baseline
5. Reduction in suppuration from baseline
6. Improvement in frequency of relapses from baseline
7. Improvement in quality of life from baseline
8. Improvement on a disease severity assessment tool from baseline
H. Graft versus host disease
All members (including new members) requesting authorization for continuation of therapy must meet all initial authorization
criteria.
I. All other diagnoses
Authorization of 12 months may be granted for all members (including new members) who are using the requested medication for an indication outlined in Section III and who achieve or maintain positive clinical response with the requested medication as evidenced by low disease activity or improvement in signs and symptoms of the condition.
V. OTHER
For all indications: Member has had a documented negative TB test (which can include a tuberculosis skin test [PPD], an
interferon-release assay [IGRA], or a chest x-ray)* within 6 months of initiating therapy for persons who are naïve to biologic
DMARDs or targeted synthetic DMARDs associated with an increased risk of TB, and repeated yearly for members with risk
factors** for TB that are continuing therapy with biologics.
* If the screening testing for TB is positive, there must be further testing to confirm there is no active disease. Do not administer
the requested medication to members with active TB infection. If there is latent disease, TB treatment must be started before
initiation of the requested medication.
** Risk factors for TB include: Persons with close contact to people with infectious TB disease; persons who have recently
immigrated from areas of the world with high rates of TB (e.g., Africa, Asia, Eastern Europe, Latin America, Russia); children
less than 5 years of age who have a positive TB test; groups with high rates of TB transmission (e.g., homeless persons,
injection drug users, persons with HIV infection); persons who work or reside with people who are at an increased risk for
active TB (e.g., hospitals, long-term care facilities, correctional facilities, homeless shelters).
For all indications: Member cannot use the requested medication concomitantly with any other biologic DMARD or targeted
synthetic DMARD.
VI. DOSAGE AND ADMINISTRATION
Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-
based practice guidelines. Dose optimization with 50 mg product formulations should be used when possible. Exceptions for
higher quantities of 25 mg vials will be allowed when the member has a latex allergy or is following FDA-approved weight-based
dosing.
VII. APPENDICES
Appendix A: Examples of Contraindications to Methotrexate
1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease, or other chronic liver disease
2. Breastfeeding
3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia)
4. Elevated liver transaminases
5. History of intolerance or adverse event
6. Hypersensitivity
7. Interstitial pneumonitis or clinically significant pulmonary fibrosis
8. Myelodysplasia
9. Pregnancy or currently planning pregnancy
10. Renal impairment
11. Significant drug interaction
Appendix B: Examples of Clinical Reasons to Avoid Pharmacologic Treatment with Methotrexate, Cyclosporine or
Acitretin.
1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease, or other chronic liver disease
2. Breastfeeding
3. Drug interaction
4. Cannot be used due to risk of treatment-related toxicity
5. Pregnancy or currently planning pregnancy
6. Significant comorbidity prohibits use of systemic agents (examples include liver or kidney disease, blood dyscrasias,
uncontrolled hypertension)
APPENDIX C: Risk factors for articular juvenile idiopathic arthritis
1. Positive rheumatoid factor
2. Positive anti-cyclic citrullinated peptide antibodies
3. Pre-existing joint damage
Special Notes:
VII. APPENDICES
Appendix A: Examples of Contraindications to Methotrexate
1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease, or other chronic liver
disease
2. Breastfeeding
3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia)
4. Elevated liver transaminases
5. History of intolerance or adverse event
6. Hypersensitivity
7. Interstitial pneumonitis or clinically significant pulmonary fibrosis
8. Myelodysplasia
9. Pregnancy or currently planning pregnancy
10. Renal impairment
11. Significant drug interaction
Appendix B: Examples of Clinical Reasons to Avoid Pharmacologic Treatment with
Methotrexate, Cyclosporine or Acitretin.
1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease, or other chronic liver
disease
2. Breastfeeding
3. Drug interaction
4. Cannot be used due to risk of treatment-related toxicity
5. Pregnancy or currently planning pregnancy
6. Significant comorbidity prohibits use of systemic agents (examples include liver or kidney
disease, blood dyscrasias, uncontrolled hypertension)
APPENDIX C: Risk factors for articular juvenile idiopathic arthritis
1. Positive rheumatoid factor
2. Positive anti-cyclic citrullinated peptide antibodies
3. Pre-existing joint damage
Place of Service:
Outpatient
The above policy is based on the following references:
1. Enbrel [package insert]. Thousand Oaks, CA: Immunex Corporation; August 2020.
2. van der Heijde D, Ramiro S, Landewe R, et al. 2016 Update of the international ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017;0:1-14.
3. Flagg SD, Meador R, Hsia E, et al. Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: an open-label trial. Arthritis Rheum. 2005;53(4):613-617.
4. IBM Micromedex® DRUGDEX® System (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www.micromedexsolutions.com/ (cited: 02/18/2021).
5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655.
6. 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.
7. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784.
8. 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. 2019;71(6):717-734. doi:10.1002/acr.23870.
9. Menter A, Gottlieb A, Feldman SR, et al. Guidelines for the management of psoriasis and psoriatic arthritis. Section 1: Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850.
10. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 6: Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65(1):137-174.
11. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies; 2015 update. Ann Rheum Dis. 2016;75(3):499-510.
12. Gladman DD, Antoni C, P Mease, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(Suppl II):ii14–ii17.
13. Peluso R, Lervolino S, Vitiello M, et al. Extra-articular manifestations in psoriatic arthritis patients. [Published online ahead of print May 8, 2014]. Clin Rheumatol. 2014. Accessed August 22, 2014.
14. Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011;70:896–904.
15. Ward MM, Deodhar A, Gensler LS, et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-1613. doi:10.1002/art.41042.
16. Martin PJ, Rizzo JD, Wingard JR, et al. First and second line systemic treatment of acute graft versus host disease: Recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 18:1150-1163, 2012.
17. Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behcet’s syndrome. Ann Rheum Dis. 2018.; 77: 808-818.
18. Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029-1072.
19. Tuberculosis (TB). TB risk factors. Centers for Disease Control and Prevention. Retrieved on 05 August 2020 from: https://www.cdc.gov/tb/topic/basics/risk.htm.
20. Singh JA, Guyatt G, Ogdie A, et al. 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019;71(1):5-32. doi:10.1002/art.40726.
21. Flores D, Marquez J, Garza M, Espinoza LR. Reactive arthritis: newer developments. Rheum Dis Clin North Am. 2003;29(1):37-vi.
22. The NCCN Drugs & Biologics Compendium 2020 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed August 10, 2020.
23. Lexicomp [database online]. Hudson, OH: Lexi-Comp, Inc.; https://online.lexi.com/lco/action/home [available with subscription]. Accessed August 2020.
24. Menter, A, Cordero, KM, Davis, DM, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82(1):161-201.
25. Menter, A, Gelfand, JM, Connor, C, et al. Joint AAD-NPF guidelines of care for the management of psoriasis with systemic nonbiologic therapies. J Am Acad Dermatol. 2020;82(6): 1445-86.
26. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation (HCT): Pre-Transplant Recipient Evaluation and Management of Graft-Versus-Host Disease. Version 2.2020. https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf. Accessed August 10, 2020.
27. George, C, Deroide, F, Rustin, M. Pyoderma gangrenosum – a guide to diagnosis and management. Clin Med. 2019;19(3): 224-8.
28. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019; 81(1): 76-90.
29. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019; 81(1): 91-101.
30. Smolen JS, Aletaha D. Assessment of rheumatoid arthritis activity in clinical trials and clinical practice. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Available with subscription. URL: www.uptodate.com. Accessed March 19, 2021.
Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
December 30, 2021
