immunomodulators – oral and subcutaneous...behcet's disease humira quantity limits apply :...

of 32 Coverage Policy Number: 2102 Immunomodulators: Cigna Total Savings Plans

Drug and Biologic Coverage Policy

Effective Date .......................................... 4/15/2021 Next Review Date… .................................... 1/1/2022 Coverage Policy Number .................................. 2102

Immunomodulators – Oral and Subcutaneous (Cigna Total Savings Drug List)

Table of Contents Overview .............................................................. 1 Coverage Policy ................................................... 2 Reauthorization Criteria ..................................... 12 Authorization Duration ....................................... 12 Conditions Not Covered..................................... 12 FDA Approved Indications ................................. 13 Recommended Dosing ...................................... 14 General Background .......................................... 23 Coding/ Billing Information ................................. 28 References ........................................................ 29

Related Coverage Resources Abatacept Intravenous Golimumab Intravenous Immunomodulators (Individual and Family Plans) Immunomodulators- Employer Group (Standard,

Value, Legacy Drug Lists) Infliximab Natalizumab for Crohn’s Disease Oncology Medications Quantity Limitations Rituximab for Non-Oncology Indications Tocilizumab Intravenous Vedolizumab

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Overview This coverage policy addresses the use of oral and subcutaneous immunomodulators for the following Employer Group Benefit Plans: Cigna Total Savings Drug List Plans

• Coverage for Employer Group Plans (Standard/Performance, Value/Advantage, Legacy Drug List Plans) is addressed in a separate policy.

• Coverage for Individual and Family Benefit Plans is addressed in a separate coverage policy. • Coverage for intravenous immunomodulators for are addressed in separate coverage policies.

Please refer to the related coverage policy links above.

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0006_coveragepositioncriteria_abatacept_iv.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0007_coveragepositioncriteria_golimumab_iv.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_1903_coveragepositioncriteria_immunomodulators_IFP.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_1805_coveragepositioncriteria_immunomodulators.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_1805_coveragepositioncriteria_immunomodulators.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0003_coveragepositioncriteria_infliximab.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0008_coveragepositioncriteria_natalizumab_CD.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_1403_coveragepositioncriteria_oncology.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_1201_coveragepositioncriteria_quantity_limits.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ph_5108_coveragepositioncriteria_rituximab_rituxan.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0004_coveragepositioncriteria_tocilizumab_iv.pdf

https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/m_0005_coveragepositioncriteria_vedolizumab.pdf


Oral and Subcutaneous Immunomodulators for Cigna Total Savings Plans include the following:

• Actemra® subcutaneous injection (tocilizumab)

• Cimzia® (certolizumab pegol)

• Cosentyx® (secukinumab)

• Enbrel® (etanercept) • Humira® (adalimumab)

• Ilumya™ (tildrakizumab-asmn)

• Kevzara™ (sarilumab) • Kineret® (anakinra) • Olumiant® (baricitinib) • Orencia® subcutaneous

injection (abatacept) • Otezla® (apremilast) • Rinvoq (upadacitinib) • Siliq™ (brodalumab)

• Simponi® (golimumab) • Skyrizi™

(risankizumab-rzaa) • Stelara® (ustekinumab) • Taltz® (ixekizumab) • Tremfya™

(guselkumab) • Xeljanz®/Xeljanz

XR®/Xeljanz® Oral Solution (tofacitinib)

Coverage Policy Coverage for Immunomodulators varies across plans. Refer to the customer’s benefit plan document for coverage details. For Cigna Total Savings Drug List Plans: Immunomodulators are covered as medically necessary when the condition specific and preferred product requirement criteria are met: List of Conditions: Ankylosing Spondylitis Behcet’s Disease Cryopyrin-Associated Periodic Syndromes (CAPS) Crohn’s Disease – Adults and Pediatrics Giant Cell Arteritis Graft versus Host Disease Hidradenitis Suppurativa Non-Radiographic Axial Spondyloarthritis (nr-axSpA) Plaque Psoriasis – Adults Plaque Psoriasis - Pediatrics and Adolescents

Polyarticular Juvenile Idiopathic Arthritis (PJIA) Psoriatic Arthritis Pyoderma Gangrenosum Rheumatoid Arthritis Sarcoidosis Scleritis Still’s Disease Systemic Juvenile Idiopathic Arthritis (SJIA) Ulcerative Colitis – Adult Ulcerative Colitis – Pediatric and Adolescent Uveitis

Documentation: When documentation is required, the prescriber must provide written documentation supporting the trials of these other agents. Documentation may include, but is not limited to, chart notes, prescription claims records, and/or prescription receipts When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to Immunomodulators. Note: Receipt of sample product does not satisfy any criteria requirements for coverage. Ankylosing Spondylitis

Ankylosing Spondylitis Criteria Preferred Products: Cimzia, Cosentyx, Enbrel, (1)

Non-Preferred Products with Step Therapy Requirements: Humira, Simponi SC 50mg, Taltz, (1 and 2)

1. Individual has a diagnosis of ankylosing spondylitis and BOTH of the following criteria are met:

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the


prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE non-steroidal anti-inflammatory drug (NSAID)†

b. Prescribed by, or in consultation with a rheumatologist or prescriber who specializes in ankylosing spondylitis

2. Step Requirements: When there is documentation of ONE of the following:

a. The individual has had inadequate efficacy OR contraindication according to FDA label OR significant intolerance to the covered alternatives* specified in the table below, OR

b. The individual is not a candidate intolerance to the covered alternatives* specified in the table below due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

Quantity Limits apply

Ankylosing Spondylitis Covered Alternatives* Cigna Total Savings Drug List:

For Humira, Simponi SC 50 mg, Taltz: TWO of the following:

Cimzia Cosentyx Enbrel

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Behcet’s Disease

Product Behcet’s Disease Criteria: Enbrel Quantity Limits Apply

Individual has a diagnosis of Behcet’s Disease and BOTH of the following criteria are met:

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE systemic conventional therapy† (for example, corticosteroids [such as methylprednisolone], immunosuppressants [such as azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, or tacrolimus], or colchicine)

b. Prescribed by, or in consultation with a rheumatologist, dermatologist, ophthalmologist, gastroenterologist, neurologist, or prescriber who specializes in Behcet's disease

Humira Quantity Limits Apply

Individual has a diagnosis of Behcet’s Disease and the following criteria are met:

Either (a or b) AND (c): a. Individual has ophthalmic manifestations of Behcet’s

disease b. Documentation of inadequate efficacy OR contraindication

according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE systemic conventional therapy† (for example, corticosteroids [such as methylprednisolone], immunosuppressants [such as azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, or tacrolimus], or colchicine)


Product Behcet’s Disease Criteria: c. Prescribed by, or in consultation with a rheumatologist,

dermatologist, ophthalmologist, gastroenterologist, neurologist, or prescriber who specializes in Behcet's disease

Otezla Quantity Limits apply

Individual has a diagnosis of Behcet’s Disease AND the following criteria: (a, b, and c)

a. Treatment of oral ulcers or other mucocutaneous involvement

b. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE systemic conventional therapy† (for example, corticosteroids [such as methylprednisolone], immunosuppressants [such as azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, or tacrolimus], or colchicine)

c. Prescribed by, or in consultation with a rheumatologist, dermatologist, ophthalmologist, gastroenterologist, neurologist or prescriber who specializes in Behcet's disease

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Cryopyrin-Associated Periodic Syndromes (CAPS)

Product Cryopyrin-Associated Periodic Syndromes (CAPS) Criteria: Kineret Quantity Limits apply

Individual has a diagnosis of Cryopyrin-Associated Periodic Syndromes (CAPS) and BOTH of the following criteria are met: (a and b)

a. Treatment of at least ONE of the following: o Neonatal-Onset Multisystem Inflammatory Disease

(NOMID) o Familial Cold Autoinflammatory Syndrome (FCAS) o Muckle-Wells Syndrome (MWS) o Chronic infantile neurological cutaneous and articular

(CINCA) syndrome b. Prescribed by, or in consultation with a rheumatologist,

geneticist, dermatologist, or a prescriber who specializes in CAPS

Crohn’s Disease – Adults and Pediatrics

Crohn’s Disease – Adults and Pediatrics Criteria Preferred Products: Cimzia, Stelara SC, (1)

Non-Preferred Products with Step Therapy Requirements: Humira, (1 and 2)

1. Individual has a diagnosis of moderate to severe Crohn's Disease and ALL of the following criteria are

met: [a and b] a. Individual is either of the following ages:

• (For Humira) 6 years of age or older • (For Cimzia and Stelara) 18 years of age or older

b. Prescribed by, or in consultation with a gastroenterologist or a prescriber who specializes in Crohn's disease






Crohn’s Disease – Adults and Pediatrics Covered Alternatives* Cigna Total Savings Drug List:

For Humira: Two of the following:

Cimzia Stelara SC

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Giant Cell Arteritis

Product Giant Cell Arteritis Criteria: Actemra Subcutaneous Injection Quantity Limits apply

Individual has a diagnosis of Giant cell arteritis (GCA) and BOTH of the following criteria are met: (a and b)

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE systemic corticosteroid (for example, prednisone)

b. Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in giant cell arteritis

Graft versus Host Disease

Product Graft versus Host Disease Criteria: Enbrel Quantity Limits apply

Individual has a diagnosis of Graft versus host disease and BOTH of the following criteria are met: (a and b)

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE systemic conventional treatment (for example, high-dose corticosteroids, antithymocyte globulin, cyclosporine, thalidomide, tacrolimus, or mycophenolate mofetil) OR taking one of these agents concurrently with etanercept

b. Prescribed by, or in consultation with an oncologist, hematologist, or a physician affiliated with a transplant center

Hidradenitis Suppurativa

Product Hidradenitis Suppurativa Criteria: Humira Quantity Limits apply

Individual has a diagnosis of Hidradentitis suppurativa and BOTH of the following criteria are met: (a and b) a. Documentation of inadequate efficacy OR contraindication according

to FDA label, OR significant intolerance, OR is not a candidate due


Product Hidradenitis Suppurativa Criteria: to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE conventional treatment (for example, intralesional or oral corticosteroids [such as triamcinolone, prednisone], systemic antibiotics [for example, clindamycin, dicloxacillin, or erythromycin], or isotretinoin)

b. Prescribed by, or in consultation with a dermatologist or a prescriber who specializes in hidradentitis suppurativa

Non-Radiographic Axial Spondyloarthritis (nr-axSpA)

Non-Radiographic Axial Spondyloarthritis (nr-axSpA) Criteria Preferred Products: Cimzia and Cosentyx, (1)

Non-Preferred Products with Step Therapy Requirements: Taltz: (1 and 2)

a. Individual has a diagnosis of Non-Radiographic Axial Spondyloarthritis (nr-axSpA) and the following

criteria are met: a. Individual has objective signs of inflammation, defined as ONE of the following:

o C-reactive protein (CRP) elevated beyond the upper limit of normal for the reporting laboratory

o Sacroiliitis reported on magnetic resonance imaging (MRI) b. Prescribed by or in consultation with a rheumatologist or a prescriber who specializes in nr-axSpA

b. Step Requirements: When there is documentation of ONE of the following:

a. The individual has had inadequate efficacy OR contraindication according to FDA label OR significant intolerance to the of covered alternatives* specified in the table below, OR

b. The individual is not a candidate for the covered alternatives* specified in the table below, due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

Quantity Limits apply Non-Radiographic Axial Spondyloarthritis (nr-axSpA) Covered Alternatives*

Cigna Total Savings Drug List: For Taltz: TWO of the following:

Cimzia Cosentyx

Plaque Psoriasis – Adults

Plaque Psoriasis – Adults Criteria Preferred Products: Cimzia, Cosentyx, Enbrel, Stelara SC, Tremfya, (1)

Non-Preferred Products with Step Therapy Requirements: Otezla, Humira, Ilumya, Skyrizi, Siliq, Taltz, (1 and 2)

1. Individual has a diagnosis of Chronic plaque psoriasis and ALL of the following criteria are met: (a,b,c, and

d) a. Individual is age 18 and older b. Body Surface Area (BSA) of greater than 5% OR BSA less than 5% and there is and there is

involvement of the scalp, face, the palms and soles (i.e., palmoplantar disease), or genitals c. Documentation of inadequate efficacy OR contraindication according to FDA label, OR

significant intolerance, OR is not a candidate due to being subject to a warning per the


prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to any of the following†:

• Systemic therapy (for example, methotrexate, cyclosporine, Soriatane) • Phototherapy [narrow or broad band ultraviolet B (UVB), or psoralen plus ultraviolet

A (PUVA)] • Topical therapy (for example, coal tar, keratolytics, corticosteroids, anthralin,

Dovonex, Tazorac)] d. Prescribed by or in consultation with a dermatologist or a prescriber who specializes in plaque

psoriasis 2. Step Requirements: When there is documentation of ONE of the following:



Quantity Limits apply Plaque Psoriasis – Adults Covered Alternatives*

Cigna Total Savings Drug List: For Otezla: ONE of the following:

Cimzia Cosentyx Enbrel Stelara SC Tremfya

For Humira, Ilumya, Skyrizi, Siliq, Taltz: THREE of the following:

Cimzia Cosentyx Enbrel Stelara SC Tremfya

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Plaque Psoriasis - Pediatrics and Adolescents

Product Plaque Psoriasis - Pediatrics and Adolescents Criteria: Enbrel Stelara SC Taltz Quantity Limitations apply

Individual has a diagnosis of Chronic plaque psoriasis and the following criteria are met: (a,b,and c) a. Individual is ONE of the following ages:

• For Enbrel: 4 years of age to less than 18 years of age • For Stelara SC: 12 6 years of age to less than 18 years of age • For Taltz: 6 years of age to less than 18 years of age

b. Body Surface Area (BSA) of greater than 5% OR BSA less than 5% and there is and there is involvement of the scalp, face, the palms and soles (i.e., palmoplantar disease), or genitals.

c. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to any of the following†: • Systemic therapy (for example, methotrexate, cyclosporine, Soriatane) • Phototherapy [narrow or broad band ultraviolet B (UVB), or psoralen plus ultraviolet

A (PUVA)] • Topical therapy (for example, coal tar, keratolytics, corticosteroids, anthralin,

Dovonex, Tazorac)] d. Prescribed by or in consultation with a dermatologist, or a prescriber who specializes in

plaque psoriasis †NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent.


Polyarticular Juvenile Idiopathic Arthritis (PJIA)

Polyarticular Juvenile Idiopathic Arthritis (PJIA) Criteria Preferred Products: Enbrel, Actemra SC: (1)

Non-Preferred Products with Step Therapy Requirements: Humira, Orencia SC, Xeljanz/ Xeljanz Oral Solution (1 and 2)

1. Individual has a diagnosis of Polyarticular Juvenile Idiopathic Arthritis and BOTH of the following criteria are

met: a. Individual is 2 years of age and older b. Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in PJIA


a. The individual has had inadequate efficacy OR contraindication according to FDA label OR significant intolerance to the covered alternatives* specified in the table below OR

b. The individual is not a candidate to the covered alternatives* specified in the table below due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation


Polyarticular Juvenile Idiopathic Arthritis (PJIA) Covered Alternatives* Cigna Total Savings Drug List

For Humira, Orencia SC, Xeljanz/ Xeljanz Oral Solution: TWO of the following:

Enbrel Actemra SC

Psoriatic Arthritis

Psoriatic Arthritis Criteria Preferred Products: Cimzia, Cosentyx, Enbrel, Stelara SC, (1)

Non-Preferred Products with Step Therapy Requirements: Otezla, Humira, Orencia SC, Simponi SC 50 mg, Taltz, Tremfya, Xeljanz XR (1 and 2)

1. Individual has a diagnosis of Psoriatic Arthritis and BOTH of the following criteria are met:

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to first line therapy: ONE disease-modifying anti-rheumatic drug (DMARD) (for example, methotrexate, leflunomide, sulfasalazine)†

b. Prescribed by, or in consultation with a rheumatologist, dermatologist or a prescriber who specializes in psoriatic arthritis



b. The individual is not a candidate to the covered alternatives* specified in the table below due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation



Psoriatic Arthritis Covered Alternatives* Cigna Total Savings Drug List

For Otezla: ONE of the following:

Cimzia Cosentyx Enbrel Stelara SC

For Humira, Orencia SC, Simponi SC 50 mg, Taltz, Tremfya, Xeljanz XR: TWO of the following:

Cimzia Cosentyx Enbrel Stelara SC

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Pyoderma Gangrenosum

Product Pyoderma Gangrenosum Criteria Enbrel Humira Quantity Limits apply

Individual has a diagnosis of diagnosis of Pyoderma Gangrenosum and BOTH of the following criteria are met:

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to topical corticosteroids AND systemic corticosteroids† (for example, prednisone) AND an immunosuppressant† (for example, mycophenolate mofetil and cyclosporine) for at least 2 months

b. Prescribed by, or in consultation with a dermatologist, rheumatologist or prescriber who specializes in pyoderma gangrenosum

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Rheumatoid Arthritis

Rheumatoid Arthritis Criteria Preferred Products: Actemra SC, Cimzia, Enbrel, Olumiant, (1)

Non-Preferred Products with Step Therapy Requirements: Humira, Orencia SC, Simponi SC 50 mg, Kevzara, Kineret, Rinvoq, Xeljanz (1 and 2)

1. Individual has a diagnosis of Rheumatoid Arthritis is and BOTH of the following criteria are met: a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR

significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to first line therapy: ONE disease-modifying anti-rheumatic drug (DMARD) (for example, methotrexate, leflunomide, sulfasalazine)†

b. Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in rheumatoid arthritis

2. Step Requirements: When there is documentation of ONE of the following: a. The individual has had inadequate efficacy OR contraindication according to FDA label OR

significant intolerance to the covered alternatives* specified in the table below, OR b. The individual is not a candidate to the covered alternatives* specified in the table below due to

being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

Quantity Limit applies


Rheumatoid Arthritis Covered Alternatives* Cigna Total Savings Drug List

For Humira, Orencia SC, Simponi SC 50 mg, Kevzara, Kineret, Rinvoq, Xeljanz: TWO of the following:

Actemra SC Cimzia Enbrel Olumiant

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Sarcoidosis

Product Sarcoidosis Criteria Humira Quantity Limits apply

Individual has a diagnosis of sarcoidosis and BOTH of the following criteria are met: 1. Documentation of inadequate efficacy OR contraindication according

to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to first line therapy: one corticosteroid AND one immunosuppressant (for example, methotrexate, cyclophosphamide, azathioprine)

2. Prescribed by, or in consultation with a pulmonologist, ophthalmologist, dermatologist, rheumatologist or a prescriber who specializes in sarcoidosis

Scleritis

Product Scleritis Criteria Enbrel Humira Quantity Limits apply

Individual has a diagnosis of scleritis and BOTH of the following criteria are met: a. Documentation of inadequate efficacy OR contraindication according

to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE other therapy for this condition (for example, oral NSAIDs [for example, indomethacin], oral, topical [ophthalmic] or IV corticosteroids [for example, prednisone, prednisolone, methylprednisolone]; methotrexate; cyclosporine; or other immunosupressants)

b. Prescribed by, or in consultation with an ophthalmologist

Still’s Disease

Product Still’s Disease Criteria Enbrel Kineret Quantity Limits apply

Individual has a diagnosis of Still’s Disease and BOTH of the following criteria are met: a. Documentation of inadequate efficacy OR contraindication according

to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to first line therapy: ONE corticosteroid (for example, prednisone)†AND ONE conventional synthetic disease-modifying antirheumatic drug (DMARD) [for example, methotrexate]

b. Prescribed by, or in consultation with a rheumatologist or a prescriber who specializes in Still’s Disease


†given for at least 2 months

Systemic Juvenile Idiopathic Arthritis (SJIA)

Product Criteria for Use: SJIA Actemra Subcutaneous Injection (tocilizumab) Kineret (anakinra) Quantity Limits apply

Individual has a diagnosis of Systemic Juvenile Idiopathic Arthritis (SJIA) and the following criteria is met: • Prescribed by or in consultation with a rheumatologist or a prescriber

who specializes in Systemic Juvenile Idiopathic Arthritis (SJIA)

Ulcerative Colitis - Adult

Ulcerative Colitis Criteria Preferred Products: Simponi SC 100 mg, Stelara SC, (1)

Non-Preferred Products with Step Therapy Requirements: Humira, Xeljanz/ XR, (1 and 2)

1. Individual has a diagnosis of moderate to severe Ulcerative Colitis and BOTH of the following criteria are

met: a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant

intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to ONE conventional therapy: (for example, aminosalicylate, corticosteroids or immunosuppressants)† OR Individual has pouchitis AND has tried therapy with an antibiotic (for example, metronidazole, ciprofloxacin), corticosteroid enema, or mesalamine enema

b. Prescribed by, or in consultation with a gastroenterologist or a prescriber who specializes in ulcerative colitis

2. Step Requirements: When there is documentation of ONE of the following: a. The individual has had inadequate efficacy OR contraindication according to FDA label OR significant

intolerance to the covered alternatives* specified in the table below, OR b. The individual is not a candidate to the covered alternatives* specified in the table below due to being

subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

Quantity Limit applies When criteria are met, a single intravenous infusion dose of Stelara (IV) up to a maximum dose of 520 mg will be authorized. The maintenance dosage of 90 mg subcutaneous will be authorized for 8 weeks after the initial intravenous dose, then every 8 weeks thereafter.

Ulcerative Colitis Covered Alternatives* Cigna Total Savings Drug List

For Humira or Xeljanz/XR: ONE of the following:

Simponi SC 100 mg Stelara SC

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Ulcerative Colitis – Pediatric and Adolescent


Product Criteria for Use: Ulcerative Colitis – Pediatric and Adolescent Humira Quantity Limits apply

Individual has a diagnosis of ulcerative colitis and meets ALL of the following criteria: a. Individual is ≥ 5 years of age; <18 years of age b. EITHER of the following: i) Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to: ONE conventional therapy: (for example, aminosalicylate, corticosteroids or immunosuppressants) † ii) Individual has pouchitis AND has tried therapy with an antibiotic (for example, metronidazole, ciprofloxacin), corticosteroid enema/suppository, or mesalamine enema/suppository c. Prescribed by, or in consultation with, a gastroenterologist or a prescriber who specializes in ulcerative colitis

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Uveitis

Product Criteria for Use: Uveitis Humira Quantity Limits apply

Individual has a diagnosis of Uveitis (including intermediate, posterior and panuveitis) AND BOTH of the following:

a. Documentation of inadequate efficacy OR contraindication according to FDA label, OR significant intolerance, OR is not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions to conventional therapy (such as corticosteroids or immunosuppressive drugs [for example, azathioprine, cyclosporine, or methotrexate])†

b. Prescribed by, or in consultation with an ophthalmologist, rheumatologist or a prescriber who specializes in uveitis

†NOTE: An exception to this requirement can be made if the individual has already tried a biologic. These individuals are not required to “step back” and try a conventional agent. Reauthorization Criteria Immunomodulators are considered medically necessary for continued use when initial criteria are met AND documentation of beneficial response. Authorization Duration Initial approval duration is 12 months unless otherwise stated. Conditions Not Covered Immunomodulators are considered experimental, investigational or unproven for ANY other use including the following (this list may not be all inclusive): • Concomitant use with any other biologic including all non-tumor necrosis factor (non-TNF) biologics, anti-

TNF biologics, or oral immunomodulatory agents for example, Otezla or Xeljanz/ Xeljanz XR Anti-Tumor Necrosis Factor (Anti-TNF) Biologics:


• Granulomatosis with polyangitis • Enbrel for Crohn’s Disease

Kineret (anakinra):

• Ankylosing spondylitis • Chronic infantile neurological, cutaneous and articular syndrome, treatment-refractory • Gout • Gouty arthritis • Inflammatory bowel disease arthritis • Pericarditis • Reactive arthritis

Otezla (apremilast):

• Alopecia areata • Ankylosing spondylitis • Vitiligo

Xeljanz/Xeljanz XR (tofacitinib)

• Alopecia areata • Plaque psoriasis • Vitiligo

COVID-19 (Coronavirus Disease 2019)

• Olumiant (baricitinib) • Rinvoq (upadacitinib) • Xeljanz®/Xeljanz XR® (tofacitinib) (including use in cytokine release syndrome associated with COVID-

19) FDA Approved Indications Refer to Tables 1,2, and 3 Table 1. Approved TNFis for Selected Indications.

Rheumatology Dermatology Gastroenterology RA JIA AS nr-axSpA PsA PsO CD UC

Cimzia √ -- √ √ √ √ √ -- Enbrel √ √ √ -- √ √ -- -- Humira √ √ √ -- √ √ √ √ Inflectra √ -- √ -- √ √ √ √ Remicade √ -- √ -- √ √ √ √ Renflexis √ -- √ -- √ √ √ √ Simponi SC

√ -- √ -- √ -- -- √

Simponi Aria

√ -- √ -- √ -- -- --

TNFis – Tumor necrosis factor inhibitors; RA – Rheumatoid arthritis; JIA – Juvenile idiopathic arthritis; AS – Ankylosing spondylitis; PsA – Psoriatic arthritis; PsO – Plaque psoriasis; CD – Crohn’s disease; UC – Ulcerative colitis. Simponi SC recommended dosing for all indications except UC is 50 mg monthly; For UC, Simponi SC follows an induction dosage regimen with 200-mg subcutaneous injection at Week 0, followed by 100 mg at Week 2, and then maintenance therapy with 100 mg every 4 weeks.


Table 2. Approved IL-17, IL-23, and IL-12/23 Blockers for Selected Indications. Rheumatology Dermatolog

y Gastroenterology

RA JIA AS PsA PsO CD UC Cosentyx -- -- √ √ √ -- -- Ilumya -- -- -- -- √ -- -- Siliq -- -- -- -- √ -- -- Skyrizi -- -- -- -- √ -- -- Stelara SC -- -- -- √ √ √^ √^ Stelara IV -- -- -- -- -- √# √# Taltz -- -- √ √ √ -- -- Tremfya -- -- -- -- √ -- -- IL – Interleukin; RA – Rheumatoid arthritis; JIA – Juvenile idiopathic arthritis; AS – Ankylosing spondylitis; PsA – Psoriatic arthritis; PsO – Plaque psoriasis; CD – Crohn’s disease; UC – Ulcerative colitis; ̂ Maintenance dosing only; # Induction dosing only.

Table 3. Other Biologics and tsDMARDs Approved for Selected Indications. Rheumatology Dermatolog

y Gastroenterology

RA JIA AS PsA PsO CD UC Actemra IV √ √^ -- -- -- -- -- Actemra SC

√ √^ -- -- -- -- --

Kevzara √ -- -- -- -- -- -- Kineret √ -- -- -- -- -- -- Olumiant √ -- -- -- -- -- -- Orencia IV √ √# -- √ -- -- -- Orencia SC √ √# -- √ -- -- -- Otezla -- -- -- √ √ -- -- Rinvoq √ -- -- -- -- -- -- Rituxan IV √ -- -- -- -- -- -- Olumiant √ -- -- -- -- -- -- Xeljanz/XR √ √± -- √ -- -- -- tsDMARDs – Targeted synthetic disease-modifying antirheumatic drugs; RA – Rheumatoid arthritis; JIA – Juvenile idiopathic arthritis; AS – Ankylosing spondylitis; PsA – Psoriatic arthritis; PsO – Plaque psoriasis; CD – Crohn’s disease; UC – Ulcerative colitis; IV – Intravenous; ^ Indicated in polyarticular and systemic JIA; # Indicated in polyarticular JIA ± XELJANZ/XELJANZ Oral Solution is indicated for the treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients 2 years of age and older.

Recommended Dosing FDA Recommended Dosing

Brand Condition FDA Recommended Dosing Actemra Rheumatoid Arthritis

Actemra may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion or as a subcutaneous injection. Recommended Intravenous (IV) Dosing Regimen: The recommended dosage of Actemra for adult patients given as a 60-minute single intravenous drip infusion is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. Reduction of dose from 8 mg per kg to 4 mg per kg is recommended for management of certain dose-related


Brand Condition FDA Recommended Dosing laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia. Doses exceeding 800 mg per infusion are not recommended in RA patients. Recommended Subcutaneous (SQ) Dosing Regimen:

• Patients less than 100 kg weight: 162mg administered subcutaneously every other week, followed by an increase to weekly dosing based on clinical response

• Patients at 100 kg weight or greater: 162mg administered subcutaneously every week

Giant Cell Arteritis

The recommended dose of Actemra for adult patients with GCA is 162 mg given once every week as a subcutaneous injection in combination with a tapering course of glucocorticoids. A dose of 162 mg given once every other week as a subcutaneous injection in combination with a tapering course of glucocorticoids may be prescribed based on clinical considerations. Actemra can be used alone following discontinuation of glucocorticoids.

• Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration (2.8)].

• Intravenous administration is not approved for GCA. Polyarticular Juvenile Idiopathic Arthritis (PJIA)

Recommended Intravenous PJIA Dosage Every 4 Weeks

Patients less than 30 kg weight 10 mg per kg Patients at or above 30 kg weight 8 mg per kg

Recommended Subcutaneous PJIA Dosage Patients less than 30 kg weight 162 mg once every 3 weeks

Patients at or above 30 kg weight 162 mg once every 2 weeks

Systemic Juvenile Idiopathic Arthritis (SJIA)

Recommended Intravenous SJIA Dosage Every 2 Weeks


Recommended Subcutaneous SJIA Dosage Patients less than 30 kg weight 162 mg once every two weeks

Patients at or above 30 kg weight 162 mg once every week

Cytokine Release Syndrome (CRS)

Recommended Intravenous CRS Dosage


Alone or in combination with corticosteroids • If no clinical improvement in the signs and symptoms of CRS

occurs after the first dose, up to 3 additional doses of Actemra may be administered. The interval between consecutive doses should be at least 8 hours.


Brand Condition FDA Recommended Dosing • Doses exceeding 800 mg per infusion are not recommended in

CRS patients. • Subcutaneous administration is not approved for CRS.

Cimzia Crohn’s Disease

The recommended initial adult dose of is 400 mg (given as two subcutaneous injections of 200 mg) initially, and at weeks 2 and 4. In patients who obtain a clinical response, the recommended maintenance regimen is 400 mg every four weeks.

Rheumatoid Arthritis

The recommended dose of for adult patients with rheumatoid arthritis is 400 mg (given as two subcutaneous injections of 200 mg) initially and at weeks 2 and 4, followed by 200 mg every other week. For maintenance dosing, 400 mg every 4 weeks can be considered.

Psoriatic Arthritis The recommended dose of Cimzia for adult patients with psoriatic arthritis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at week 2 and 4, followed by 200 mg every other week. For maintenance dosing, Cimzia 400 mg every 4 weeks can be considered

Ankylosing Spondylitis

The recommended dose of CIMZIA for adult patients with ankylosing spondylitis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.

Non-radiographic Axial Spondyloarthritis

The recommended dose of Cimzia for adult patients with non-radiographic axial spondyloarthritis is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every 2 weeks or 400 mg every 4 weeks.

Plaque Psoriasis The recommended dose of Cimzia for adults with moderate-to-severe plaque psoriasis is 400 mg (given as 2 subcutaneous injections of 200 mg each) every other week. For some patients (with body weight of ≤ 90 kg), Cimzia 400 mg (given as 2 subcuteanous injections of 200 mg each) initially and at Weeks 2 and 4, followed by 200 mg every other week can be considered.

Cosentyx Plaque Psoriasis

The recommended dose is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Each 300 mg dose is given as 2 subcutaneous injections of 150 mg. For some patients, a dose of 150 mg may be acceptable.

Psoriatic Arthritis

For psoriatic arthritis patients with coexistent moderate to severe plaque psoriasis, use the dosing and administration recommendations for plaque psoriasis.

For other psoriatic arthritis patients, administer Cosentyx with or without a loading dosage by subcutaneous injection. The recommended dosage:

• With a loading dosage is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter

• Without a loading dosage is 150 mg every 4 weeks • If a patient continues to have active psoriatic arthritis,

consider a dosage of 300 mg. Cosentyx may be administered with or without methotrexate.

Ankylosing Spondylitis

Administer Cosentyx with or without a loading dosage by subcutaneous injection. The recommended dosage:

• With a loading dosage is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter

• Without a loading dosage is 150 mg every 4 weeks.


Brand Condition FDA Recommended Dosing Enbrel Adults for Rheumatoid

Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

The recommended dose is 50 mg per week given as one subcutaneous injection or 25 mg given twice weekly as a subcutaneous injection. Doses higher than 50 mg per week are not recommended.

Plaque Psoriasis

Adult Plaque Psoriasis: The recommended starting dose is 50 mg given subcutaneously twice weekly, for three months followed by a reduction to a maintenance dose of 50mg once weekly. Pediatric Plaque Psoriasis: 63 kg (138 pounds) or more: Recommended dose is 50mg weekly Less than 63 kg (138 pounds): Recommended dose is 0.8 mg/kg weekly, with a maximum of 50 mg per week To achieve pediatric doses other than 25 mg or 50 mg, use reconstituted Enbrel lyophilized powder. Doses of Enbrel higher than those described above have not been studied in pediatric patients.

Juvenile Idiopathic Arthritis

63 kg (138 pounds) or more: Recommended dose is 50mg weekly Less than 63 kg (138 pounds): Recommended dose is 0.8 mg/kg weekly, with a maximum of 50 mg per week To achieve pediatric doses other than 25 mg or 50 mg, use reconstituted Enbrel lyophilized powder. Doses of Enbrel higher than those described above have not been studied in pediatric patients. In JIA patients, glucocorticoids, NSAIDs, or analgesics may be continued during treatment with Enbrel.

Humira Adult Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Ankylosing Spondylitis

40 mg administered every other week as a subcutaneous injection.

Juvenile Idiopathic Arthritis or Pediatric Uveitis

The recommended dose of Humira for patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) or pediatric uveitis is based on weight as shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with Humira.

Patients (2 years of age and older) Dose 10 kg (22 lbs) to <15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to < 30 kg (66 lbs) 20 mg every other week

≥ 30 kg (66 lbs) 40 mg every other week Humira has not been studied in patients with polyarticular JIA or pediatric uveitis less than 2 years of age or in patients with a weight below 10 kg.

Crohn's Disease

The recommended Humira dose regimen for adult patients with Crohn’s disease is 160 mg initially on Day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later (Day 15). Two


Brand Condition FDA Recommended Dosing weeks later (Day 29) begin a maintenance dose of 40 mg every other week. Aminosalicylates and/or corticosteroids may be continued during treatment. Azathioprine, 6-mercaptopurine (6-MP) or MTX may be continued during treatment with Humira if necessary. The use of Humira in Crohn’s disease beyond one year has not been evaluated in controlled clinical studies.

Pediatric Crohn’s Disease

The recommended Humira dose regimen for pediatric patients 6 years of age and older with Crohn’s disease (CD) is based on body weight as shown below for pediatric patients: 17 kg (37 lbs) to < 40 kg (88 lbs): • Induction: 80 mg on Day 1 (administered as two 40 mg injections

in one day); • 40 mg two weeks later (on Day 15) • Maintenance Dose Starting at Week 4 (Day 29): 20 mg every

other week ≥ 40 kg (88 lbs) • Induction: 160 mg on Day 1 (administered as four injections in

one day or as two 40 mg injections per day for two consecutive days);

• 80 mg two weeks later (on Day 15) (administered as two 40 mg injections in one day)

• Maintenance Dose Starting at Week 4 (Day 29): 40 mg every other week

Plaque Psoriasis or Uveitis

The recommended dose of Humira for adult patients with plaque psoriasis (Ps) or Uveitis (UV) is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. The use of Humira in moderate to severe chronic Ps beyond one year has not been evaluated in controlled clinical studies.

Hidradenitis Suppurativa

Body Weight of Adolescent Patients (12 years of age and

older)

Recommended Dosage Regimen

30 kg (66 lbs) to < 60 kg (132 lbs) • 80 mg initially on Day 1; and • 40 mg on Day 8 and subsequent doses: 40 mg every other week

≥ 60 kg (132 lbs) • 160 mg initially on Day 1 (given in one day or split over two consecutive days); • 80 mg on Day 15; and • 40 mg on Day 29 and subsequent doses: 40 mg every week

Ulcerative Colitis The recommended dose regimen for adult patients with ulcerative colitis is 160 mg initially on day 1 (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days), followed by 80 mg two weeks later (day 15). Two weeks later (day 29) continue with a dose of 40 mg every other week. Only continue Humira in patients who have shown evidence of clinical remission by eight weeks of therapy. Aminosalicylates and/or corticosteroids may be continued during treatment. Azathioprine and 6-mercaptopurine (6-MP) may be continued during treatment if necessary.


Brand Condition FDA Recommended Dosing Kevzara Rheumatoid Arthritis Kevzara may be used as monotherapy or in combination with

methotrexate (MTX) or other conventional DMARDs. The recommended dosage of Kevzara is 200 mg once every two weeks given as a subcutaneous injection. Reduce dose to 150 mg once every two weeks for management of neutropenia, thrombocytopenia and elevated liver enzymes

Kineret Rheumatoid Arthritis

The recommended dose of Kineret for the treatment of patients with RA is 100 mg/day administered daily by subcutaneous injection. Higher doses did not result in a higher response. The dose should be administered at approximately the same time every day.

Cryopyrin-Associated Periodic Syndromes (CAPS)

The recommended starting dose of Kineret is 1-2 mg/kg for NOMID patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation. Adjust doses in 0.5 to 1.0 mg/kg increments. Once daily administration is generally recommended, but the dose may be split into twice daily administrations.

Orencia Adult Rheumatoid Arthritis (RA)

For adult patients with RA, Orencia may be administered as an intravenous infusion or as a subcutaneous injection. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Intravenous Dosing Regimen Orencia lyophilized powder should be reconstituted and administered after dilution as a 30-minute intravenous infusion utilizing the weight range based dosing specified in the package insert. Following the initial intravenous administration, an intravenous infusion should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.

Dose of Orencia for Intravenous Infusion in Adult RA Patients Body Weight Dose Number of

Vials Less than 60 kg 500 mg 2

60 to 100 kg 750 mg 3 More than 100 kg 1000 mg 4

Each vial provides 250 mg of abatacept for administration.

Subcutaneous Dosing Regimen Orencia 125 mg in prefilled syringes or in Orenica ClickJect autoinjector should be administered by subcutaneous injection once weekly and may be initiated with or without an intravenous loading dose. For patients initiating therapy with an intravenous loading dose, Orencia should be initiated with a single intravenous infusion (as per body weight categories listed in Table 1), followed by the first 125 mg subcutaneous injection administered within a day of the intravenous infusion. Patients transitioning from Orencia intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose.

Juvenile Idiopathic Arthritis

For patients with juvenile idiopathic arthritis (JIA), Orencia may be administered as an intravenous infusion (6 years of age and older) or


Brand Condition FDA Recommended Dosing a subcutaneous injection (2 years of age and older). Intravenous dosing has not been studied in patients younger than 6 years of age. Orencia may be used as monotherapy or concomitantly with methotrexate. Intravenous Dosing Regimen Orencia should be administered as a 30-minute intravenous infusion based on body weight. Pediatric patients with:

• body weight less than 75 kg should be administered Orencia at a dose of 10 mg/kg

• body weight of 75 kg or more should be administered Orencia following the adult intravenous dosing regimen (see Table 1), not to exceed a maximum dose of 1000 mg.

Following the initial administration, Orencia should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. Any unused portions in the vials must be immediately discarded. Subcutaneous Dosing Regimen Orencia for subcutaneous injection should be initiated without an intravenous loading dose and be administered utilizing the weight range-based dosing as specified in Table 2.

Dose of Orencia for Subcutaneous Administration in Patients 2 Years of Age or Older with JIA

Body Weight of Patient Dose (once weekly) 10 to less than 25 kg 50 mg 25 to less than 50 kg 87.5 mg 50 kg or more 125 mg

The safety and efficacy of Orencia ClickJect autoinjector for subcutaneous injection has not been studied in patients under 18 years of age.

Adult Psoriatic Arthritis

For adult patients with psoriatic arthritis, Orencia may be administered as an intravenous infusion (IV) or a subcutaneous (SC) injection. Orencia can be used with or without non-biologic DMARDs. Intravenous Dosing Regimen Orencia IV should be administered as a 30-minute intravenous infusion utilizing the weight range-based dosing specified in Table 1. Following the initial intravenous administration, an intravenous infusion should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. Subcutaneous Dosing Regimen Orencia SC 125 mg should be administered by subcutaneous injection once weekly without the need for an intravenous loading dose. Patients switching from Orencia intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose.

Otezla Psoriatic Arthritis Dosage Titration Schedule


Brand Condition FDA Recommended Dosing Psoriasis Behcet’s Disease

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 and

thereafter AM AM PM AM PM AM PM AM PM AM PM 10 mg

10 mg

10 mg

10 mg

20 mg

20 mg

20 mg

20 mg

30 mg

30 mg

30 mg

Rinvoq Rheumatoid Arthritis The recommended oral dose of Rinvoq is 15 mg once daily with or without food

Rinvoq may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs

Siliq Plaque Psoriasis The recommended Siliq dose is 210 mg administered by subcutaneous injection at Weeks 0,1, and 2 followed by 210 mg every 2 weeks. If an adequate response has not been achieved after 12 to 16 weeks of treatment with SILIQ, consider discontinuing therapy. Continued treatment beyond 16 weeks in patients who have not achieved an adequate response is not likely to result in greater success.

Simponi Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

The Simponi dose regimen is 50 mg administered by subcutaneous (SC) injection once a month. For patients with rheumatoid arthritis (RA), Simponi should be given in combination with methotrexate. For patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS), Simponi may be given with or without methotrexate or other non-biologic DMARDs. For patients with RA, PsA, or AS, corticosteroids, non-biologic DMARDs, and/or NSAIDs may be continued during treatment with Simponi.

Ulcerative Colitis The recommended Simponi induction dosage regimen is a 200 mg subcutaneous injection at week 0, followed by 100 mg at week 2 and then maintenance therapy with 100 mg every 4 weeks.

Skyrizi Plaque Psoriasis The recommended dose is 150 mg (two 75 mg injections) administered by subcutaneous injection at Week 0, Week 4, and every 12 weeks thereafter.

Stelara Plaque Psoriasis

• For patients weighing <100 kg (220 lbs), the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks.

• For patients weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.

In subjects weighing >100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects.

General Considerations for Administration of Stelara Stelara is for subcutaneous administration. Stelara is intended for use under the guidance and supervision of a physician. Stelara should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. After proper training in subcutaneous injection technique, a patient may self inject with Stelara if a physician determines that it is


Brand Condition FDA Recommended Dosing appropriate. Patients should be instructed to follow the directions provided in the Medication Guide.

Psoriatic Arthritis The recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. For patients with co-existent moderate-to-severe plaque psoriasis weighing >100 kg (220 lbs), the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks.

Crohn’s Disease, Ulcerative Colitis

Intravenous Induction Adult Dosage Regimen A single intravenous infusion dose of Stelara using the weight-based dosage regimen specified in Table [see Instructions for dilution of Stelara 130 mg vial for intravenous infusion (2.6)]. Initial Intravenous Dosage of Stelara

Body Weight of Patient at time of dosing

Dose Number of 130mg/26ml (5mg/ml) Stelara vials

55kg or less 260mg 2 More than 55kg to 85kg 390mg 3 More than 85 kg 520mg 4

Subcutaneous Maintenance Adult Dosage Regimen The recommended maintenance dosage is a subcutaneous 90 mg dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter.

Taltz Plaque Psoriasis Taltz is administered by subcutaneous injection. The recommended dose is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

Psoriatic Arthritis The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at week 0, followed by 80 mg every 4 weeks. For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for plaque psoriasis. Taltz may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).

Tremfya Plaque Psoriasis Tremfya is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.

Psoriatic Arthritis Tremfya is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter. Tremfya may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).

Xeljanz/ Xeljanz XR

Rheumaroid Arthritis Xeljanz/Xeljanz XR may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).


Brand Condition FDA Recommended Dosing The recommended dose of Xeljanz is 5 mg twice daily and the recommended dose of Xeljanz XR is 11 mg once daily.

Psoriatic Arthritis Xeljanz/Xeljanz XR is used in combination with nonbiologic disease modifying antirheumatic drugs (DMARDs) in psoriatic arthritis. The efficacy of Xeljanz/Xeljanz XR as a monotherapy has not been studied in psoriatic arthritis. The recommended dose of Xeljanz is 5 mg twice daily and the recommended dose of Xeljanz XR is 11 mg once daily.

Ulcerative Colitis The recommended dose of Xeljanz is 10mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Discontinue after 16 weeks of 10 mg twice daily, if adequate therapeutic benefit is not achieved. Use the lowest effective dose to maintain response. The recommended dose of Xeljanz XR for induction is 22 mg once daily for at least 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed continue 22 mg once daily for a maximum of 16 weeks. Discontinue 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. The maintenance dose is 11 mg once daily. See full prescribing information for dosage adjustments by indication.

Xeljanz/ Xeljanz

Oral Solution

Polyarticular Juvenile Idiopathic Arthritis

XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or substitutable with XELJANZ Oral Solution. Dosing is weight based. See full prescribing information for dosage adjustments by clinical variables such as renal impairment, use of a strong CYP3A4 inhibitors, and hematologic parameters.

• 10 kg ≤ body weight <20 kg: 3.2 mg (3.2 mL oral solution) twice daily

• 20 kg ≤ body weight <40 kg: 4 mg (4 mL oral solution) twice daily

• Body weight ≥40 kg: 5 mg (one 5 mg tablet or 5 mL oral solution) twice daily

General Background Pharmacology Abatacept, a selective costimulation modulator, inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of RA and PsA and are found in the synovium of patients with RA and PsA. Anakinra blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Anti-TNF agents bind specifically to TNF-alpha and block its interaction with the cell surface TNF receptors. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. TNF promotes the synthesis of other proinflammatory cytokines, stimulates endothelial cells to express adhesion molecules that attract leukocytes into affected joints, accelerates the production of metalloproteinases, and inhibits the synthesis of cartilage proteoglycans. Increased concentrations of TNF also are found in psoriatic plaques. TNF blockers modulate responses that are induced or regulated by TNF, including expression of adhesion molecules, serum


concentrations of matrix metalloproteinase, and serum concentrations of cytokines. Two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface of TNFR. Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor that decreases pro-inflammatory mediators and increases anti-inflammatory mediators. Brodalumab is a human monoclonal IgG2 antibody that selectively binds to human IL-17RA and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer and IL-25. IL-17RA is a protein expressed on the cell surface and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. Blocking IL17RA inhibits IL-17 cytokine-induced responses including the release of pro-inflammatory cytokines and chemokines. Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines implicated in the pathogenesis of psoriasis. Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines. Sarilumab binds soluble IL-6 receptors (sIL-6R) and membrane-bound IL-6 receptors (mIL-6R), inhibiting IL 6 mediated signaling. This in turn reduces T-cell activation and other inflammatory effects associated with synovial proliferation and joint destruction in patients with RA. Secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis. Tofacitinib inhibits Janus kinase (JAK) enzymes. These enzymes play roles in cytokine and growth factor signaling in humans thereby affecting hematopoiesis and immune cell function. The JAK enzymes block the phosphorylation and thus activation of transcription and signal transducers. Because of this inhibition, some intracellular activity (e.g., gene expression) does not occur. Tofacitinib displays functional selectivity for JAK1 and 3 more than JAK2. (Yazici, 2011; Zerbini, 2012) However, the relevance of this selectivity to efficacy is unknown. Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs. Ustekinumab is an immunoglobulin G1-kappa monoclonal antibody specific to the p40 subunits of IL-12 and IL-23. Ustekinumab binds to IL-12 and IL-23 preventing them from activating IL-12R-beta1 receptors on various


immune and inflammatory cells. Specific effects of this binding include preventing natural killer cell and IL-17 activation, reducing interferon-gamma production, and reducing CD4+ T-cell differentiation and activation. Professional Societies/Organizations Behcet’s Disease EULAR recommendations (2018) include TNFis for initial or recurrent sight-threatening uveitis. (Hatemi, 2018) For patients refractory to first-line treatments (e.g., corticosteroids), TNFis are among the treatment options for mucocutaneous manifestations, venous thrombosis, severe or refractory gastrointestinal disease, and recurrent/chronic joint involvement. Recommendations for the use of TNFis in ocular inflammatory disorders from the American Academy of Ophthalmology (AAO) [2014] notes that TNFis may be used first-line in patients with ophthalmic manifestations of Behcet’s disease and for acute exacerbations of pre-existing Behcet’s disease. (Levy-Clark, 2014) Crohn’s Disease The American College of Gastroenterology (ACG) has guidelines for Crohn’s disease (2018). (Lichtenstein, 2018) TNFis are listed as an option for disease that is resistant to corticosteroids, severely active disease, perianal fistulizing disease, and maintenance of remission. In post-operative Crohn’s disease, a TNFi should be started within 4 weeks of surgery to prevent recurrence. Graft versus Host Disease Guidelines (2012) generally recommend TNFis as a treatment option following a trial of first-line agent(s) [e.g., cyclosporine, intravenous methylprednisolone] for acute GVHD (grade III or IV disease). (Dignan, 2012) A number of small studies demonstrate efficacy when etanercept was used in GVHD. (Wolff, 2005, Choi 2012, Levine, 2008, Alousi, 2009, Busca, 2007, Kennedy 2006) Juvenile Idiopathic Arthritis (JIA) In polyarticular disease, the 2019 ACR recommendations propose initial DMARD treatment with a conventional synthetic DMARD such as MTX in most patients prior to a TNFi. In those who are secondary nonresponders to a TNFi, a second TNFi may be tried; however, a non-TNF biologic is recommended for primary nonresponders. TNFis may also be used as second- or third-line treatment for systemic JIA. (Ringold, 2013) Plaque Psoriasis Guidelines from the American Academy of Dermatologists (AAD) and National Psoriasis Foundation (NPF) [2019] recommend adalimumab as a monotherapy treatment option for adults with moderate to severe disease. (Menter, 2019)

Psoriatic Arthritis Guidelines from ACR (2019) recommend TNFis over other biologics for use in treatment-naïve patients with PsA and in those who were previously treated with an oral therapy. (Singh, 2019) Rheumatoid Arthritis Guidelines from the American College of Rheumatology (ACR) [2015] have TNF inhibitors and non-TNF biologics, administered with or without MTX, equally positioned as a recommended therapy following a trial of a conventional synthetic DMARD (e.g., MTX, leflunomide, hydroxychloroquine, sulfasalazine). (Singh, 2016)

Spondyloarthritis Guidelines from the Assessment of SpondyloArthritis International Society (ASAS)/EULAR (2016) recommend biologics (e.g., TNFis, Cosentyx) in patients with persistently high disease activity despite traditional conventional treatments (e.g., nonpharmacological management, NSAIDs). (van der Heijde, 2017) Purely axial disease should not be treated with conventional synthetic DMARDs. Guidelines from the American College of Rheumatology (ACR) and the Spondyloarthritis Research and Treatment Network (SPARTAN) [2015] recommend TNFis for patients with active disease despite treatment with an NSAID (includes patients with non-radiographic axial [nr-ax]SpA). (Ward, 2016) Predominantly axial manifestations are not recommended for a conventional synthetic DMARD prior to a TNFi. However, for symptomatic peripheral arthritis, a conventional synthetic DMARD is recommended (preferably sulfasalazine).


Ulcerative Colitis Updated ACG guidelines for UC (2019) note that the following agents can be used for induction of remission in moderately to severely active disease: Uceris (budesonide tablets); oral or intravenous systemic corticosteroids, Entyvio (vedolizumab injection), Xeljanz (tofacitinib tablets), or TNFis (adalimumab, Simponi SC, infliximab).

(Rubin, 2019) In addition to the approved indication, clinical guidelines for the management of pouchitis, published in 2009 indicate that first-line therapy for pouchitis is antibiotic therapy (e.g. metronidazole, ciprofloxacin). (Pardi, 2009) Other treatment options include maintenance probiotics, oral or topical budesonide, anti-inflammatory drugs (e.g., mesalamine), or immunosuppressive drugs (e.g., Remicade).

Ocular Inflammatory Disorders The American Academy of Ophthalmology (AAO) [2014] note that Humira may be used in patients with uveitis due to various causes (e.g., spondyloarthropathy-associated or human leukocyte antigen [HLA]-B27-associated uveitis, JIA-associated uveitis, and other posterior uveitides and panuveitis syndromes). (Levy-Clark, 2014) Humira should be considered second-line in vision-threatening JIA-associated uveitis when MTX has failed or is not tolerated (strong recommendation) and may be used as corticosteroid-sparing treatment for vision-threatening chronic uveitis from seronegative spondyloarthropathy (strong recommendation). Humira may also be considered in other patients who have vision-threatening or corticosteroid-dependent disease who have failed first-line therapies. Humira should be considered as a second-line immunomodulatory agent for severe ocular inflammatory conditions including chronic and severe scleritis. Pyoderma Gangrenosum Although guidelines are not current, multiple topical and systemic therapies have been used for pyoderma gangrenosum. Oral prednisone is the most common initial immunosuppressant medication. (Dabade, 2011) Other systemic therapies include cyclosporine, MTX, azathioprine, cyclophosphamide, mycophenolate mofetil, Remicade, Enbrel, and Humira. In case reports, TNFis have been effective. Sarcoidosis Recommendations for best practice in the management of pulmonary and systemic sarcoidosis recommend glucocorticoids as first-line therapy. (Amin, 2014) Patients who cannot be weaned to a prednisone-equivalent dose of < 10 mg/day are appropriate candidates for steroid-sparing treatment with cytotoxic agents (e.g., MTX, azathioprine, leflunomide). If these agents fail or cause toxicity, Humira, Remicade, cyclophosphamide, or mycophenolate mofetil are proposed. Spondyloarthritis Guidelines for ankylosing spondylitis and nonradiographic axial spondylitis are published by the American College of Rheumatology (ACR)/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network (2019). (Ward, 2019) TNFis are recommended for the initial biologic. In those who are secondary nonresponders to a TNFi, a second TNFi is recommended over switching out of the class. Still’s Disease: There are not current guidelines for treatment of Still’s disease. However, it presents in adults with features similar to those of systemic onset JIA. (Riera, 2011) In addition, there is a small trial which demonstrated efficacy of etanercept used for this condition. Biosimilars According to the FDA, a biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product. There may be minor differences in clinically inactive components of the product. (FDA, 2017) In the ACR guidelines for treatment of Crohn’s disease, the organization states that biosimilar forms of infliximab and adalimumab effectively treat moderate to severe Crohn’s disease and may be used in both initial induction and maintenance phases of treatment. Furthermore, the guideline mentions the current lack of evidence supporting the safety and efficacy of changing from one biosimilar to another of the same biosimilar molecule in individuals who have stable disease and are in maintenance phase (Lichtenstein, 2018). According to The Task


Force on the Use of Biosimilars to Treat Rheumatological Disorders, participation by prescribers and patients is important in the decision to switch between biosimilars (Kay, 2018). Other Uses without Supportive Evidence Anakinra Treatment of Recurrent Idiopathic Pericarditis, AIRTRIP, was a double blind, placebo controlled, multicenter, randomized withdrawal trial conducted among 21 corticosteroid dependent patients. During the six month treatment phase, pericarditis recurrence was observed in 18% in the Kineret group and 90% of the placebo group. The authors stated that in this preliminary study in patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of Kineret reduced the risk of recurrence over a median of 14 months compared to placebo. Additional studies are needed to further evaluate efficacy as well as to examine safety. (Brucato, 2016) Anakinra has also been studied for use in ankylosing spondylitis, gout, gouty arthritis, inflammatory bowel disease arthritis, and reactive arthritis. At this time, however, there is insufficient published data in terms of safety and efficacy to support its use in these indications. Apremilast Apremilast has been studied for use in ankylosing spondylitis. At this time, however, there is insufficient published data in terms of safety and efficacy to support its use for this indication. Etanercept Etanercept has been studied in individuals with moderate to severe Crohn’s disease. Patients received subcutaneous etanercept 25 mg or placebo twice weekly. In the primary outcome, at week 4, 39% of patients taking etanercept had a clinical response as compared with 45% with placebo. Findings demonstrated that etanercept at the dose studied was not effective for the treatment of patients with moderate to severe Crohn's disease. (Sandborn, 2001) Wegener's Granulomatosis Etanercept Trial (WGET) Research Group evaluated etanercept plus standard therapy for Wegener's granulomatosis. The primary outcome was sustained remission which was defined in this study as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis of zero for at least six months. Patients did receive glucocorticoids plus cyclophosphamide or methotrexate in addition to active treatment or placebo. There were no significant differences between the etanercept and control groups in the rates of sustained remission, sustained periods of low-level disease activity, or the time required to achieve those measures. The research group determined that etanercept is not effective for the maintenance of remission in patients with Wegener's granulomatosis. (WGET, 2005) Tocilizumab There is insufficient evidence in the peer-reviewed published scientific literature to support safety and efficacy of tocilizumab in uveitis. Tofacitinib Therapies for alopecia areata (AA) are addressed in the British Association of Dermatologists’ guidelines for the management of alopecia areata. According to the guidelines, mild forms of alopecia areata have high rates of spontaneous remission, which makes evaluation of treatment difficult. In the severe form of the condition, there are low spontaneous remission rates, and these individuals often do not respond to any type of treatment. The organization states that there many case studies of treatments, but overall, there is a lack of randomized controlled trials (the exception being contact immunotherapy) and publications demonstrating long-term outcomes. Despite reports of various therapies which can promote hair growth in alopecia areata, none are capable of modifying the long-term course of the condition. The guidelines further state that use of anti-tumor necrosis factor (anti TNF) drugs are ineffective, and cites a number of reports where alopecia areata has happened in individuals receiving these drugs for other diseases. (Messenger, 2012)

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wegener%27s%20Granulomatosis%20Etanercept%20Trial%20(WGET)%20Research%20Group%5BCorporate%20Author%5D


Tofacitinib was studied retrospectively in 90 individuals with AA and at least 40% loss of scalp hair. The primary endpoint was the percent change in the Severity of Alopeica Tool (SALT) score. Prospective reponders to treatment were described as individuals with alopecia totalis or alopecia universalis with a duration of current disease of 10 years or less, or alopecia areata. Seventy-seven percent of the prospective responders had a clinical response, with 58% of the individuals reaching a greater than 50% change in SALT score over 4-18 month duration of treatment. Those with the highest percentage in SALT score change tended to be those with AA, compared to those with alopecia totalis or alopecia universalis. Limitations of the study include retrospective data, small sample size and no control group. The authors state that although efficacy was seen for AA in the short-term, there is no long term data and randomized controlled trials are needed. (Liu, 2017a) There are reports of anti-TNF drugs being used in a topical formulation, however, these drugs are not FDA approved for topical application. (Iorizzo, 2018; Luzhou, 2014) A small case series of 10 individuals with vitiligo were treated with JAK inhibitors. Five subjects achieved some repigmentation at sites of either sunlight exposure or low dose nbUVB light. The authors stated that JAK monotherapy does not seem to be effective, but appears to need concurrent nbUVB phototherapy or sunlight exposure. The authors concluded that prospective clinical trials are necessary to evaluate the use of JAK inhibitors in vitiligo. This study was limited by small sample size, retrospective design and no control group. (Liu, 2017b) In a review of JAK inhibitor use in dermatology found the strongest evidence for the use of these drugs is in treating psoriasis. The authors reference data regarding the potential efficacy of these drugs in alopecia areata and vitiligo but further study is necessary, particularly head to head studies of the JAK inhibitors compared to current standard therapies. (Ciechanowicz, 2018) In October 2015, the manufacturer of tofacitinib received a Complete Response Letter from the FDA denying its supplemental New Drug Application (sNDA) for treatment of adults with moderate to severe chronic plaque psoriasis. The use of tofacitinib was evaluated in adults with moderate-to-severe active Crohn’s disease (Crohn’s Disease Activity Score [CDAI] of 220-450). The primary endpoint was clinical response at 4 weeks (defined as a reduction in CDAI score of at least 70 points from baseline). Results demonstrated There was not a significant difference between any of the tofacitinib dose groups and placebo in clinical response. In addition, a secondary endpoint of clinical remission (defined as a CDAI score of less than 150 at 4 weeks) was not significantly different between the treatment groups and placebo. (Sandborn, 2014) Coding/ Billing Information Note: Oral and subcutaneous immunomodulators are typically covered under pharmacy benefit plans. Abatacept subcutaneous (Orencia), adalimumab (Humira), anakinra (Kineret), apremilast (Otezla), baricitinib (Olumiant), brodalumab (Siliq), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab subcutaneous (Simponi), guselkumab (Tremfya), ixekizumab (Taltz), sarilumab (Kevzara), secukinumab (Cosentyx), tocilizumab subcutaneous (Actemra), tofacitinib (Xeljanz/Xeljanz XR), and ustekizumab subcutaneous (Stelara) are typically covered under pharmacy benefit plans. Certain prescription drugs require an authorization for coverage to ensure that appropriate treatment regimens are followed. Medical drug coding and diagnosis codes, however, are generally not required for pharmacy claims submissions. Abatacept intravenous (Orencia), golimumab intravenous (Simponi Aria), and,Ttildrakizumab-asmn (Ilumya), tocilizumab intravenous (Actemra), and ustekinumab intravenous (Stelara) require medical drug coding and are listed as follows: Note: 1) This list of codes may not be all-inclusive. 2) Deleted codes and codes which are not effective at the time the service is rendered may not be eligible for reimbursement.


Considered Medically Necessary when criteria in the applicable policy statements listed above are met:

HCPCS Codes

Description

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)

J1602 Injection, golimumab, 1 mg, for intravenous use J3245 Injection, tildrakizumab, 1 mg J3358 Ustekinumab, for intravenous injection, 1 mg J3262 Injection, tocilizumab, 1 mg

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