Clinical Policy: Biologic DMARDs Reference Number: CP.CPA.194 Effective Date: Last Review Date: Line of Business: Commercial

Transcription

1 Clinical Policy: Reference Number: CP.CPA.194 Effective Date: Last Review Date: Line of Business: Commercial Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are biologic disease-modifying anti-rheumatic drugs (DMARDs) requiring prior authorization: tocilizumab (Actemra ), certolizumab pegol (Cimzia ), secukinumab (Cosentyx ), etanercept (Enbrel ), vedolizumab (Entyvio ), adalimumab (Humira ), infliximab (Remicade ), infliximab-abda (Renflexis ), infliximab-dyyb (Inflectra ), sarilumab (Kevzara ), anakinra (Kineret ), abatacept (Orencia ), apremilast (Otezla ), brodalumab (Siliq TM ), golimumab (Simponi, Simponi Aria ), ustekinumab (Stelara ), ixekizumab (Taltz ), guselkumab (Tremfya TM ), natalizumab (Tysabri ), tofacitinib (Xeljanz, Xeljanz XR). FDA Approved Indication(s) AS CD UC GCA NOMID pjia sjia PsO PsA RA HS MS UV CRS Actemra x x (IV) x (IV) x Cimzia x x x x Cosentyx x x x Enbrel x x x x x Entyvio x x Humira x x x x x x x x x Inflectra x x x x x x Kevzara x Kineret x x Orencia x x x Otezla x x Remicade x x x x x x Renflexis x x x x x x Siliq x Simponi x x x x Simponi x x x Aria Stelara x x x Taltz x Tremfya x Tysabri x x Xeljanz/ x Xeljanz XR AS=ankylosing spondylitis; CD=Crohn s disease; UC=ulcerative colitis; GCA = giant cell arteritis; NOMID=neonatal-onset multisystem inflammatory disease; pjia=polyarticular juvenile idiopathic arthritis; x (IV) Page 1 of 26

2 sjia=systemic juvenile idiopathic arthritis; PsO=plaque psoriasis; PsA= psoriatic arthritis; RA=rheumatoid arthritis; HS= Hidradenitis Suppurativa, MS=multiple sclerosis, UV = uveitis; CRS = cytokine release syndrome Contents: I. Initial Approval Criteria A. Ankylosing Spondylitis B. Crohn s Disease C. Cytokine Release Syndrome D. Giant Cell Arteritis E. Hidradenitis Suppurativa F. Neonatal-Onset Multisystem Inflammatory Disease G. Plaque Psoriasis H. Polyarticular Juvenile Idiopathic Arthritis I. Psoriatic Arthritis J. Rheumatoid Arthritis K. Systemic Juvenile Idiopathic Arthritis L. Ulcerative Colitis M. Uveitis II. Continued Therapy III. Diagnoses/Indications for which coverage is NOT authorized IV. Appendices/General Information V. Dosage and Administration VI. Product Availability VII. References Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation that Actemra, Cimzia, Cosentyx, Enbrel, Entyvio, Humira, Inflectra, Kevzara, Kineret, Orencia, Otezla, Remicade, Renflexis, Siliq, Simponi, Simponi Aria, Stelara, Taltz, Tremfya, Tysabri, Xeljanz, and Xeljanz XR are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Ankylosing Spondylitis (must meet all): 1. Diagnosis of active Ankylosing Spondylitis (AS); 2. Request is for one of the following: Humira, Cimzia, Cosentyx, Enbrel, Inflectra, Remicade, Renflexis, Simponi, or Simponi Aria; 3. Failure of a trial of at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) (at up to maximally indicated doses), each trialed for at least 1 month, unless contraindicated or clinically significant adverse effects are experienced; 4. For Cimzia or Simponi: Failure of a trial of 2 of the following, each tried for at least 3 months, unless contraindicated or clinically significant adverse effects are experienced: Humira, Enbrel, Cosentyx; 5. For Inflectra, Renflexis, or Simponi Aria: Failure of a 3-month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; Page 2 of 26

3 6. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer B. Crohn s Disease (must meet all): 1. Diagnosis of moderate-to-severe Crohn`s Disease (CD); 2. Request is for one of the following: Humira, Cimzia, Entyvio, Inflectra, Remicade, Renflexis, Stelara, Tysabri; 3. Prescribed by or in consultation with a Gastroenterologist; 4. For Cimzia or Stelara: Failure of a 3-month trial of Humira unless contraindicated or clinically significant adverse effects are experienced; 5. For Entyvio, Inflectra, Renflexis, or Tysabri: Failure of a 3-month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; 6. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer C. Cytokine Release Syndrome (must meet all): 1. Member has a scheduled chimeric antigen receptor T-cell (CAR-T) therapy (e.g., Kymriah, Yescarta); 2. Request is for an intravenous formulation of Actemra; 3. Dose does not exceed 800 mg per infusion for up to 4 total doses. Approval duration: Up to 4 total doses D. Giant Cell Arteritis (must meet all): 1. Diagnosis of giant cell arteritis (GCA); 2. Request is for subcutaneous formulation of Actemra; 3. Prescribed by or in consultation with a Rheumatologist; 4. Failure of a trial of a corticosteroid (at up to maximally tolerated doses) in conjunction with methotrexate or azathioprine for 12 weeks, unless contraindicated or clinically significant adverse effects are experienced; 5. Dose does not exceed 162 mg SC every week. Approval duration: 6 months or to member s renewal date, whichever is longer E. Hidradenitis Suppurativa (must meet all): 1. Diagnosis of Hidradenitis Suppurativa (HS); 2. Request is for Humira; 3. Prescribed by or in consultation with a Dermatologist, Rheumatologist, or Gastroenterologist; 4. Documentation of Hurley stage II or stage III; 5. Failure of a trial of systemic antibiotic therapy (at up to maximally indicated doses), unless contraindicated or clinically significant adverse effects are experienced; 6. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer F. Neonatal-Onset Multisystem Inflammatory Disease (must meet all): 1. Diagnosis of Neonatal-onset multisystem inflammatory disease (NOMID) or chronic infantile neurological, cutaneous and articular syndrome (CINCA); Page 3 of 26

4 2. Request is for Kineret; 3. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer G. Plaque Psoriasis (must meet all): 1. Diagnosis of chronic moderate-to-severe plaque psoriasis (PsO); 2. Request is for one of the following: Humira, Cosentyx, Enbrel, Inflectra, Otezla, Remicade, Renflexis, Siliq, Stelara, Taltz or Tremfya; 3. Prescribed by or in consultation with a Dermatologist or Rheumatologist; 4. Failure of a trial of one of the following therapies, either alone or in combination, unless contraindicated or clinically significant adverse effects are experienced: a. Methotrexate up to a dose of mg/week; b. If methotrexate is contraindicated, failure of PUVA Therapy or UVB, or cyclosporine or acitretin; 5. For Siliq, Stelara, Taltz, or Tremfya: Failure of a trial of Humira and Cosentyx, each tried for at least 3 months, unless contraindicated or clinically significant adverse effects are experienced; 6. For Inflectra, Renflexis, or Simponi Aria: Failure of a 3-month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; 7. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer H. Polyarticular Juvenile Idiopathic Arthritis (must meet all): 1. Diagnosis of active Polyarticular Juvenile Idiopathic Arthritis (pjia); 2. Request is for one of the following: Humira, Enbrel, Orencia, or IV Actemra, 3. Prescribed by or in consultation with a Rheumatologist; 4. Failure of a 3-month trial of MTX (at up to maximally indicated doses), unless contraindicated or clinically significant adverse effects are experienced; 5. For SC Orencia: Failure of a trial of Humira and Enbrel, each tried for at least 3 months, unless contraindicated or clinically significant adverse effects are experienced; 6. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer I. Psoriatic Arthritis (must meet all): 1. Diagnosis of active Psoriatic Arthritis (PsA); 2. Request is for one of the following: Humira, Cimzia, Cosentyx, Enbrel, Inflectra, Orencia, Otezla, Remicade, Renflexis, Simponi, Simponi Aria, or Stelara; 3. Prescribed by or in consultation with a Rheumatologist or a Dermatologist; 4. Failure of a trial of MTX (at up to maximally indicated doses) unless contraindicated or clinically significant adverse effects are experienced; 5. For Cimzia, Simponi, Stelara, or SC Orencia: Failure of a trial of Humira and Enbrel and either Otezla or Cosentyx, each tried for at least 3 months, unless contraindicated or clinically significant adverse effects are experienced; Page 4 of 26

5 6. For Inflectra, Renflexis, Simponi Aria, or IV Orencia: Failure of a 3-month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; 7. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer J. Rheumatoid Arthritis (must meet all): 1. Diagnosis of rheumatoid arthritis (RA); 2. Request is for one of the following: Humira, Actemra, Cimzia, Enbrel, Inflectra, Kevzara, Kineret, Orencia, Remicade, Renflexis, Simponi, Simponi Aria, Xeljanz, Xeljanz XR; 3. Meets one of the following (a or b): a. Prescribed by or in consultation with a Rheumatologist; b. Defined at baseline prior to DMARD treatment initiation by the American College of Rheumatology (ACR) criteria (refer to Appendix C); 4. Meets one of the following (a or b): a. If member is biologic DMARD-naïve: Failure of a trial of MTX in the last year (at up to maximally indicated doses) unless contraindicated or clinically significant adverse effects are experienced; b. If member is not a candidate for MTX (i.e., member is a smoker [increased risk of MTX lung disease] or MTX is contraindicated): Failure of a trial of sulfasalazine or 1 other conventional DMARD (at up to maximally indicated doses) unless contraindicated or clinically significant adverse effects are experienced; 5. For Xeljanz or Xeljanz XR, Failure of a trial of Humira and Enbrel, each tried for at least 3 months, unless contraindicated or clinically significant adverse effects are experienced; 6. For Cimzia, Kevzara, Kineret, Orencia, Simponi, failure of at least a 3 month trial of Humira and Enbrel, followed by Xeljanz or Xeljanz XR, unless contraindicated or clinically significant adverse effects are experienced; 7. For SC Actemra, failure of at least a 3 month trial of Humira and Enbrel, followed by Xeljanz or Xeljanz XR, and then followed by Kevzara, unless contraindicated or clinically significant adverse effects are experienced; 8. For Inflectra, Renflexis, Simponi Aria, IV Actemra, or IV Orencia: Failure of a 3- month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; 9. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer K. Systemic Juvenile Idiopathic Arthritis (must meet all): 1. Diagnosis of systemic juvenile idiopathic arthritis (sjia); 2. Request is for IV Actemra; 3. Prescribed by or in consultation with a Dermatologist, Rheumatologist, or Gastroenterologist; 4. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer Page 5 of 26

6 L. Ulcerative Colitis (must meet all): 1. Diagnosis of moderate-to-severe ulcerative colitis (UC); 2. Request is for one of the following: Humira, Entyvio, Inflectra, Remicade, Renflexis, or Simponi; 3. Prescribed by or in consultation with a Gastroenterologist; 4. Failure of a trial of azathioprine, 6-mercaptopurine, or aminosalicylate (e.g., sulfasalazine), each tried for at least 3 months at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced; 5. For Simponi: Failure of a 3-month trial of Humira unless contraindicated or clinically significant adverse effects are experienced; 6. For Entyvio, Inflectra or Renflexis: Failure of a 3-month trial of Remicade unless contraindicated or clinically significant adverse effects are experienced; 7. For Induction, member is not in remission; 8. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer M. Uveitis (must meet all): 1. Diagnosis of non-infectious intermediate, posterior, or panuveitis; 2. Request is for Humira; 3. Prescribed by or in consultation with an Ophthalmologist or Rheumatologist; 4. Failure of a trial of oral corticosteroids (e.g., prednisone) (at up to maximally indicated doses), unless contraindicated or clinically significant adverse effects are experienced; 5. Failure of a trial of non-biologic immunosuppressive therapy (e.g., azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, chlorambucil) (at up to maximally indicated doses), unless contraindicated or clinically significant adverse effects are experienced; 6. Dose does not exceed maximum dose indicated in Section V. Approval duration: 6 months or to member s renewal date, whichever is longer N. Relapsing-Remitting Multiple Sclerosis (must meet all): 1. Refer to Tysabri MS criteria. O. Other diagnoses/indications 1. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). II. Continued Therapy A. All Indications in Section I (must meet all): 1. Member meets one of the following (a or b): a. Currently receiving medication via a health plan affiliated with Centene Corporation or member has previously met initial approval criteria; b. Documentation supports that member is currently receiving Actemra for CAR-T cell-induced cytokine release syndrome (CRS) and member has not yet received 4 total doses; Page 6 of 26

7 2. Member is responding positively to therapy (e.g. labs, sign/symptom reduction, no disease progression, no significant toxicity); 3. If request is for a dose increase, new dose does not exceed maximum dose indicated in Section V. Approval duration: For CRS: up to 4 total doses For all other indications: 6 months or to member s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Centene Corporation and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off-label use policy CP.CPA.09 or evidence of coverage documents; B. Combination use with Xeljanz or biological DMARDs such as TNF antagonists [Cimzia, Enbrel, Simponi, Remicade, Inflectra, Renflexis], interleukin-1 receptor (IL-1R) antagonists [Kineret], interleukin-6 receptor (IL-6R) antagonists [Actemra, Kevzara], interleukin-17 receptor (IL-17R) antagonists [Siliq], interleukin-23 (IL-23) inhibitor [Tremfya], anti-cd20 monoclonal antibodies [Rituxan] and selective co-stimulation modulators [Orencia] because of the possibility of increased immunosuppression, neutropenia and increased risk of infection. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ACR: American College of Rheumatology AS: ankylosing spondylitis CAR: chimeric antigen receptor CD: Crohn s disease CINCA: chronic infantile neurological, cutaneous and articular syndrome CRS: cytokine release syndrome DMARDs: disease-modifying antirheumatic drugs GCA: giant cell arteritis HS: hidradenitis suppurativa, IV: intravenous MS: multiple sclerosis, MTX: methotrexate NOMID: neonatal-onset multisystem inflammatory disease NSAIDs: non-steroidal anti- inflammatory drugs pjia: polyarticular juvenile idiopathic arthritis PP: plaque psoriasis PsA: psoriatic arthritis RA: rheumatoid arthritis RA: rheumatoid arthritis SC: subcutaneous sjia: systemic juvenile idiopathic arthritis TNF: tumor necrosis factor UC: colitis ULN: upper limit of normal UV: uveitis Page 7 of 26

8 Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization. Drug Dosing Regimen Dose Limit/ Maximum Dose azathioprine (Imuran ) Rheumatoid Arthritis 1 mg/kg/day PO given as a QD or BID Crohn s Disease and Ulcerative Colitis mg PO daily Uveitis 1 mg/kg/day PO 2.5 mg/kg/day PO corticosteroids cyclosporine (Sandimmune Neoral ) hydroxychloroquine (Plaquenil ) mercaptopurine (Purinethol ) methotrexate (Rheumatrex ) Giant Cell Arteritis 2 mg/kg/day Crohn s Disease Prednisone 40 mg PO QD for 2 weeks or IV mg Q6H for 1 week budesonide (Entocort EC ) 6-9 mg PO QD Giant Cell Arteritis Various Rheumatoid Arthritis, Plaque Psoriasis mg/kg/day PO divided BID Uveitis mg/kg/day PO in divided doses Rheumatoid Arthritis Initial dose: mg PO QD Maintenance dose: mg PO QD Crohn s Disease, Ulcerative Colitis mg PO daily Rheumatoid Arthritis 7.5 mg/week PO or 2.5 mg PO Q12hr for 3 doses/week Polyarticular Juvenile Arthritis 10mg/m 2 PO weekly Plaque Psoriasis 10 to 25 mg/week, IM, IV or PO N/A N/A Do not exceed 600 mg/day (465 mg base/day) or 6.5 mg/kg/day (5 mg base/kg/day), whichever is lower. 5 mg/kg/day PO For Rheumatoid Arthritis: 20 mg/week PO For Plaque Psoriasis: 30 mg/week PO Page 8 of 26

9 Drug Dosing Regimen Dose Limit/ Maximum Dose Uveitis mg/week PO Giant Cell Arteritis mg/week Oral doses > 30 mg/m 2 are generally not recommended due to poor absorption. Pentasa (mesalamine) acitretin (Soriatane ) sulfasalazine (Azulfidine ) Crohn s Disease and Ulcerative Colitis 1000 mg PO QID Plaque Psoriasis 25 or 50 mg PO daily Rheumatoid Arthritis 2 gm/day PO in divided doses 4 g/day PO 50 mg/day PO For Rheumatoid Arthritis: 3 g/day PO. mycophenolate mofetil (Cellcept ) tacrolimus (Prograf ) cyclophosphamide (Cytoxan ) chlorambucil (Leukeran ) doxycycline minocycline Ulcerative Colitis Initial dose is 3 to 4 gm/day PO; maintenance is 2 gms/day PO. Administer in evenly divided doses (not exceeding 8-hour intervals) Uveitis 500 mg PO BID Uveitis mg/kg/day PO Uveitis 2 mg/kg/day PO Uveitis 0.1 mg/kg/day PO Hidradenitis suppurativa mg PO BID Hidradenitis suppurativa mg PO BID For Ulcerative Colitis: N/A 3 g/day PO N/A N/A N/A 300 mg/day PO 300 mg PO on day 1, then 200 mg/day PO clindamycin + rifampin Hidradenitis suppurativa clindamycin 300 mg PO BID with rifampin 300 mg PO BID clindamycin: 1,800 mg/day PO rifampin: 600 mg/day PO Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name only and generic (Brand name ) when the drug is available by both brand and generic. Appendix C: General Information The 2010 ACR Classification Criteria for RA: Classification criteria for RA (score-based algorithm: add score of categories A through D Page 9 of 26

10 *A score of 6 out of 10 is needed for classification of a patient as having definite RA) A Joint Involvement Score 1 large joint large joints small joints (with or without involvement of large joints) small joints (with or without involvement of large joints) 3 > 10 joints (at least one small joint) 5 B Serology (at least one test result is needed for classification) Negative rheumatoid factor (RF) and negative anti-citrullinated 0 protein antibody (ACPA) Low positive RF or low positive ACPA 2 High positive RF or high positive ACPA 3 C Acute phase reactants (at least one test result is needed for classification) Normal CRP and normal ESR 0 Abnormal CRP or normal ESR 1 D Duration of symptoms < 6 weeks 0 6 weeks 1 Safety: o These agents are immunosuppressive and have the potential to increase the risk of infection and reactivate latent, chronic infections. They should not be administered to patients with a clinically important infection. Caution should be used in patients with chronic infections or history of recurrent infection. If patient develops a serious infection these agents should be discontinued. o Serious infections were seen in clinical studies with concurrent use of Kineret and another TNF-blocking agent, Enbrel, with no added benefit compared to Enbrel alone. Because of the nature of the adverse reactions with this combination therapy, similar toxicities may also result from combination of anakinra and other TNF blocking agents. Rheumatoid Arthritis: o In RA, failure of MTX or DMARD is defined as a contraindication or < 50% decrease in swollen joint count, < 50% decrease in tender joint count, and < 50% decrease in ESR, or < 50% decrease in CRP, or contraindication to at least 3 months of therapy with MTX at doses up to 25 mg per week or maximum tolerated dose. Ankylosing Spondylitis: o Several ankylosing spondylitis (AS) treatment guidelines call for a trial of 2 or 3 nonsteroidal anti-inflammatory drugs (NSAID) prior to use of an anti-tnf agent. A two year trial showed that continuous NSAID use reduced radiographic progression of AS versus on demand use of NSAID. Ulcerative Colitis: o For Ulcerative Colitis maintenance therapy, failure is defined as having two or more exacerbations requiring steroid therapy. Polyarticular Juvenile Idiopathic Arthritis: o Failure of MTX in PJIA is defined as disease activity remaining moderate to high despite treatment with MTX. Page 10 of 26

11 o In PJIA, response to treatment is reflected by improvement of disease activity level and poor prognostic features including: reduction in the number of active joints, ESR or CRP, Physician global assessment, patient/parent global assessment, arthritis of the hip or cervical spine, positive RF or ACPA, radiographic damage. Xeljanz: o Per prescribing information, Xeljanz should not be used in combination with biologic DMARDs [such as Kineret] or potent immunosuppressants such as azathioprine and cyclosporine. As stated in the black box warning, patients treated with Xeljanz are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as MTX or corticosteroids. Stelara: o Stelara is for subcutaneous administration and is intended for use under the guidance and supervision of a physician. After proper training in subcutaneous injection technique, a patient may self inject with Stelara if a physician determines that it is appropriate. Patients should be instructed to follow the directions provided in the Medication Guide. o In the PHOENIX 2 trial, dosing intensification of Stelara to every 8 weeks did not result in greater efficacy compared with continuing treatment every 12 weeks. Neonatal-Onset Multisystem Inflammatory Disease: o Other names used for NOMID are as follows: chronic infantile neurological, CINCA, chronic neurologic, cutaneous, and articular syndrome, infantile onset multisystem inflammatory disease, IOMID syndrome, and Prieur-Griscelli syndrome. Enbrel: o Off-label indications: Graft vs. Host disease is listed in Micromedex as Class IIa for pediatric patients and Enbrel is recommended in most cases. Severe, refractory hidradenitis suppurativa is listed in Micromedex with an evidence rating of Class IIa for adult patients. Hidradenitis Suppurativa: o HS is sometimes referred to as: "acne inversa, acne conglobata, apocrine acne, apocrinitis, Fox-den disease, hidradenitis axillaris, HS, pyodermia sinifica fistulans, Velpeau s disease, and Verneuil s disease." o In HS, Hurley stages are used to determine severity of disease. Hurley stage II indicates moderate disease, and is characterized by recurrent abscesses, with sinus tracts and scarring, presenting as single or multiple widely separated lesions. Hurley stage III indicates severe disease, and is characterized by diffuse or near-diffuse involvement presenting as multiple interconnected tracts and abscesses across an entire area. o Enbrel has off-label use supported by some efficacy data in severe, refractory HS through retrospective cohort studies and case reports. This off-label indication for Enbrel is recommended by Micromedex with a Class IIa recommendation. Taltz: o Taltz is currently being studied for the treatment of rheumatoid arthritis, radiographic axial spondyloarthritis, ankylosing spondylitis, and psoriatic arthritis. Page 11 of 26

12 V. Dosage and Administration Indication Drug Name Dosing Regimen Maximum Dose 400 mg/dose Initial dose: Ankylosing Spondylitis 400 mg SC initially and at Weeks 2 and 4 Cimzia (certolizumab pegol) Maintenance dose: 200 mg SC every other week (400 mg SC every 4 weeks can be considered) Cosentyx (secukinumab) Initial dose: 150 mg SC at weeks 0, 1, 2, 3 and 4 (or option for no loading dose) 150 mg/dose Enbrel (etanercept) Humira (adalimumab) Remicade (infliximab), Inflectra (infliximabdyyb), Renflexis (infliximababda) Simponi (golimumab) Maintenance dose: 150 mg SC every 4 weeks 50 mg SC once weekly 40 mg SC every other week 5 mg/kg IV initially and at eeks 2 and 6, then Q6W 50 mg SC once a month 50 mg once weekly 40 mg every other week 5 mg/kg every 6 weeks 50 mg/month Crohn`s Disease Simponi Aria (golimumab) Cimzia (certolizumab pegol) 2 mg/kg IV infusion over 30 minutes at Weeks 0 and 4, then every 8 weeks Initial dose: 400 mg SC initially and at weeks 2 and 4 Maintenance dose: In patients who obtain a clinical response, 400 mg SC every 4 weeks Maintenance: 2 mg/kg every 8 weeks 400 mg/dose subcutaneously. Page 12 of 26

13 Entyvio (vedolizumab) Humira (adalimumab) 300 mg IV initially and at weeks 2 and 6, then Q8W Induction: 160 mg SC (four 40mg injections) day 1 followed by 80 mg SC 2 weeks later (day15). 160mg can be given as 4 injections in one day or divided over 2 days. Two weeks later (day 29) begin maintenance dose of 40mg SC every other week Maintenance: 40 mg SC every other week Pediatric Crohn s Disease 17 kg (37 lbs) to < 40 kg (88 lbs): Initial dose (Day 1): 80 mg (two 40 mg injections in one day) Second dose two weeks later (Day 15): 40 mg Two weeks later (Day 29): Begin a maintenance dose of 20 mg every other week. Maintenance: 300 mg every 8 weeks Maintenance: 40 mg every other week Crohn`s Disease Remicade (infliximab), Inflectra (infliximabdyyb), Renflexis 40 kg (88 lbs): Initial dose (Day 1): 160 mg (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) Second dose two weeks later (Day 15): 80 mg (two 40 mg injections in one day) Two weeks later (Day 29): Begin a maintenance dose of 40 mg every other week. 5 mg/kg IV initially and at weeks 2 and 6, then Q8W Adults: 10 mg/kg every 8 weeks Children and adolescents: 5 mg/kg every 8 weeks Page 13 of 26

14 (infliximababda) Stelara (ustekinumab) A single intravenous infusion for induction using weight-based dosing: Up to 55kg: 260 mg 55 85kg: 390 mg >85kg: 520 mg A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter. IV: Weight < 55kg: 260mg IV once; Weight 55 kg to 85kg: 390 mg IV once; Weight >85kg: 520 mg IV once. SC: 90 mg every 8 weeks Cytokine Release Syndrome Giant Cell Arteritis Hidradenitis Suppurativa Tysabri (natalizumab) Actemra (tocilizumab) Actemra (tocilizumab) Humira (adalimumab) 300 mg IV Q4W 300 mg every 4 weeks Alone or in combination with corticosteroids, as a 60-minute IV infusion: < 30 kg: 12 mg/kg IV per infusion > 30 kg: 8 mg/kg IV per infusion 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. 162 mg SC every week Initial dose (Day 1): 160 mg SC (given as four 40 mg injections on Day 1 or as two 40 mg injections per day on Days 1 and 2) Second dose two weeks later (Day 15): 80 mg SC (two 40 mg injections in one day) 4 total doses of up to 800 mg per infusion SC:162 mg every week Maintenance: 40 mg every week Page 14 of 26

15 Third (Day 29) and subsequent doses: 40 mg SC every week. Neonatal- Onset Multisystem Inflammatory Disease (NOMID) Kineret (anakinra) 1-2 mg/kg/day by SC injection. Maximum of 8 mg/kg daily. Once daily administration is generally recommended, but the dose may be split into twice daily administrations. 8 mg/kg/day Cosentyx (secukinumab) 300 mg SC at weeks 0, 1, 2, 3 and 4 followed by 300 mg SC every 4 weeks. For some patients, a dose of 150 mg may be acceptable. 300 mg/dose subcutaneously. Plaque Psoriasis Enbrel (etanercept) Adults: Starting dose: 25 mg or 50 mg or SC twice weekly for 3 months Maintenance dose: 25 mg or 50 mg SC per week Pediatric: Less than 63 kg: 0.8 mg/kg SC per week given as single injection. Maximum dose of 50 mg per week 63 kg or more: 50 mg SC per week Maintenance: 50 mg once weekly Humira (adalimumab) Initial dose of 80 mg SC followed by 40 mg SC every other week starting one week after the initial dose. Maintenance: 40 mg every other week Otezla (apremilast) Remicade (infliximab), Inflectra 30 mg PO BID after initial titration dosing 5 mg/kg IV initially and at weeks 2 and 6, then Q8W 60 mg/day PO. 5 mg/kg every 8 weeks Page 15 of 26

16 Plaque Psoriasis (infliximabdyyb), Renflexis (infliximababda) Siliq (brodalumab) Stelara (ustekinumab) Taltz (ixekizumab) 210 mg SC at Weeks 0, 1, and 2 followed by 210 mg every 2 weeks Weight < 60 kg in adolescents: 0.75 mg/kg SC initially and 4 weeks later, followed by 0.75 mg/kg SC every 12 weeks. Weight 100 kg: 45 mg SC initially and 4 weeks later, followed by 45 mg SC every 12 weeks thereafter Weight > 100 kg: 90 mg SC initially and 4 weeks later, followed by 90 mg SC every 12 weeks thereafter 160 mg (two 80 mg injections) SC at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg SC every 4 weeks Maintenance: 210 mg/2 weeks Weight < 60 kg: 0.75 mg/kg every 12 weeks Weight 100 kg: 45 mg for the first 2 doses (weeks 0 and 4 of therapy), then every 12 weeks thereafter Weight > 100 kg: 90 mg for the first 2 doses (weeks 0 and 4 of therapy), then every 12 weeks thereafter Maintenance: 80 mg/4 weeks Polyarticular Juvenile Idiopathic Arthritis Tremfya (guselkumab) Actemra (tocilizumab) 100 mg SC at Week 0 and 4, then every 8 weeks thereafter Patients less than 30 kg: 10 mg/kg IV Q 4 Weeks Patients 30 kg or more: 8 mg/kg IV Q 4 Weeks Maintenance: 100 mg/8 weeks IV: 10 mg/kg every 4 weeks Enbrel (etanercept) Less than 63 kg: 0.8 mg/kg SC per week given as single injection. Maximum dose of 50 mg per week 63 kg or more: 50 mg SC per week 50 mg once weekly Page 16 of 26

17 Humira (adalimumab) 10 kg to <15 kg = 10 mg SC every other week 15 kg to <30 kg = 20 mg SC every other week 30 kg = 40 mg SC every other week. 40 mg every other week Polyarticular Juvenile Idiopathic Arthritis Psoriatic Arthritis Orencia (abatacept) Cimzia (certolizumab pegol) Cosentyx (secukinumab) Intravenous (IV): < 75 kg: 10 mg/kg at weeks 0, 2, and 4, then every 4 weeks thereafter 75 to 100 kg: 750 mg every 2 weeks for 3 doses (i.e., a dose at weeks 0, 2, and 4), and then every 4 weeks thereafter >100 kg: 1000 mg every 2 weeks for 3 doses (i.e., a dose at weeks 0, 2, and 4), and then every 4 weeks thereafter. Subcutaneous (SC): 10 to <25 kg: 50 mg SC once weekly 25 to <50 kg: 87.5 mg SC once weekly 50 kg: 125 mg SC once weekly Initial dose: 400 mg SC initially and at Weeks 2 and 4 Maintenance dose: 200 mg SC every other week (400 mg SC every 4 weeks can be considered) Initial dose: 150 mg SC at weeks 0, 1, 2, 3 and 4 (or option for no loading dose) Maintenance dose: 150 mg SC every 4 weeks (can increase to 300 mg if needed) IV: < 75 kg: 10 mg/kg every 4 weeks; 75 to 100 kg: 750 mg every 4 weeks; >100 kg: 1000 mg every 4 weeks. SC: 10 to <25 kg: 50 mg SC once weekly; 25 to <50 kg: 87.5 mg SC once weekly; 50 kg: 125 mg SC once weekly. 400 mg/dose subcutaneously. 300 mg/dose subcutaneously. Page 17 of 26

18 Psoriatic Arthritis Enbrel (etanercept) Humira (adalimumab) Orencia (abatacept) Otezla (apremilast) Remicade (infliximab), Inflectra (infliximabdyyb), Renflexis (infliximababda) Simponi (golimumab) Simponi Aria (golimumab) Stelara (ustekinumab) 50 mg SC once weekly 50 mg once weekly 40 mg SC every other week 40 mg every other week Patients less than 60 kg: 500 mg Patients 60 kg to 100 kg: 750 mg Patients more than 100 kg: 1,000 mg IV initially then at weeks 2 and 4 then, Q 4 Weeks Or 125 mg SC Q Week. May be used following an initial IV loading dose 30 mg PO BID after initial titration dosing 5 mg/kg IV initially and at weeks 2 and 6, then Q8W IV: < 60 kg: 500 mg every 4 weeks kg: 750 mg every 4 weeks > 100 kg: 1000 mg every 4 weeks SC: 125 mg/week 60 mg/day PO. 5 mg/kg every 8 weeks 50 mg SC once a month 50 mg/month 2 mg/kg IV infusion over 30 minutes at Weeks 0 and 4, then every 8 weeks 45 mg SC initially and 4 weeks later, followed by 45 mg every 12 weeks With co-existent moderateto-severe plaque psoriasis weighing more than 100 kg: 90 mg SC initially and 4 weeks later, followed by 90 mg SC every 12 weeks Maintenance: 2 mg/kg every 8 weeks Psoriatic arthritis alone, co-existent plaque psoriasis with weight 100 kg: 45 mg for the first 2 doses (weeks 0 and 4 of therapy), then every 12 weeks thereafter; Co-existent plaque psoriasis with weight Page 18 of 26

19 Patients less than 100 kg: 162 mg SC QOW > 100 kg: 90 mg for the first 2 doses (weeks 0 and 4 of therapy), then every 12 weeks thereafter IV: 800 mg every 4 weeks Rheumatoid Arthritis Actemra (tocilizumab) Cimzia (certolizumab pegol) Enbrel (etanercept) Humira (adalimumab) Patients 100 kg or more: 162 mg SC Q Week Or 4 mg/kg IV every 4 weeks followed by an increase to 8 mg/kg IV every 4 weeks based on clinical response Initial dose: 400 mg SC initially and at Weeks 2 and 4 SC: 162 mg every week 400 mg/dose subcutaneously. Maintenance dose: 200 mg SC every other week (400 mg SC every 4 weeks can be considered) 50 mg SC once weekly 50 mg once weekly 40 mg SC every other week If not on concomitant methotrexate, may benefit from increasing the dosing frequency to 40 mg SC every week. 40 mg every other week Kevzara (sarilumab) Kineret (anakinra) Orencia (abatacept) 200 mg SC once every 2 weeks 100 mg/day by SC injection. Patients less than 60 kg: 500 mg Patients 75 kg to 100 kg: 750 mg 200 mg/2 weeks 100 mg/day IV: < 60 kg: 500 mg every 4 weeks kg: 750 mg every 4 weeks > 100 kg: 1000 mg every 4 weeks Page 19 of 26

20 Patients more than 100 kg: 1,000 mg IV initially then at weeks 2 and 4 then, Q 4 Weeks Or 125 mg SC Q Week. May be used following an initial IV loading dose SC: 125 mg/week Rheumatoid Arthritis Systemic Juvenile Idiopathic Arthritis (SJIA) Remicade (infliximab), Inflectra (infliximabdyyb), Renflexis (infliximababda) Simponi (golimumab) Simponi Aria (golimumab) Xeljanz (tofacitinib) Xeljanz XR (tofacitinib) Actemra (tocilizumab) 3 mg/kg IV initially and at weeks 2 and 6, then Q8W 10 mg/kg every 4 weeks 50 mg SC once a month 50 mg/month 2 mg/kg IV infusion over 30 minutes at Weeks 0 and 4, then every 8 weeks 5 mg PO BID 10 mg/day 11 mg PO QD Do not crush, split, or chew Xeljanz XR. Patients less than 30 kg: 12 mg/kg IV Q 2 Weeks Patients 30 kg or more: 8 mg/kg IV Q 2 Weeks Maintenance: 2 mg/kg every 8 weeks 11 mg/day IV: 12 mg/kg every 2 weeks Ulcerative Colitis Entyvio (vedolizumab) Humira (adalimumab) 300 mg IV initially and at weeks 2 and 6, then Q8W Initial dose (Day 1): 160 mg SC (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) Maintenance: 300 mg every 8 weeks Maintenance: 40 mg every other week Second dose two weeks later (Day 15): 80 mg SC Page 20 of 26

21 Ulcerative Colitis Remicade (infliximab), Inflectra (infliximabdyyb), Renflexis (infliximababda) Simponi (golimumab) Two weeks later (Day 29): Begin a maintenance dose of 40 mg SC every other week. Maintenance: 40 mg SC every other week 5 mg/kg IV initially and at weeks 2 and 6, then Q8W 200 mg SC at week 0, 100 mg SC at week 2, then 100 mg SC every 4 weeks 5 mg/kg every 8 weeks Maintenance: 100 mg/month Uveitis Humira (adalimumab) Initial dose of 80 mg SC followed by 40 mg SC every other week starting one week after the initial dose. Maintenance: 40 mg every other week VI. Product Availability Drug Name Availability Actemra Single-use vial: 80 mg/4 ml, 200 mg/10 ml, 400 mg/20 ml (tocilizumab) Single-dose prefilled syringe: 162 mg/0.9 ml Cimzia Vial: 200 mg lyophilized powder (certolizumab Single-use prefilled syringe: 200 mg/ml pegol) Cosentyx (secukinumab) Enbrel (etanercept) Entyvio (vedolizumab) Humira (adalimumab) Vial: 150 mg lyophilized powder (for healthcare professional use only) Syringe: 150 mg/ml; carton of 1 or 2 syringes Pen: 150 mg/ml (Sensoready ); carton of 1 or 2 pens Multi-use vials: 25 mg Single-use pre-filled syringes: 25 mg/0.5 ml, 50 mg/ml Pre-filled SureClick Autoinjector: 50 mg/ml Enbrel Mini TM single-dose prefilled cartridge for use with AuthoTouch TM reusable autoinjector: 50 mg/ml Single-use vial: 300 mg/20 ml Pre-filled Pen Carton: 2 dose trays. Each dose tray contains a singleuse 40mg/0.8ml pen. Page 21 of 26

22 Inflectra (infliximab-dyyb) Kevzara (sarilumab) Kineret (anakinra) Orencia (abatacept) Otezla (apremilast) Remicade (infliximab) Renflexis (infliximab-abda) Siliq (brodalumab) Simponi (golimumab) Simponi Aria (golimumab) Stelara (ustekinumab) Taltz (ixekizumab) Tremfya (guselkumab) Tysabri Crohn`s Disease/Ulcerative Colitis Starter Package: 6 dose trays. Each dose tray contains a single-use 40mg/0.8ml prefilled pen. Pre-filled Syringe Carton: 40mg: 2 dose trays. Each dose tray contains a single-use 40mg/0.8ml prefilled syringe. Pre-filled Syringe Carton: 20 mg: 2 dose trays. Each dose tray contains a single-use 20mg/0.4ml prefilled syringe. Pre-filled Syringe Carton: 10 mg: 2 dose trays. Each dose tray contains a single-use 10 mg/0.2 ml prefilled syringe. Pediatric Crohn s Disease Starter Package: 3 dose trays or 6 dose trays. Each dose tray contains a single-use 40 mg/0.8 ml prefilled syringe. Psoriasis/Uveitis Starter Package: 4 dose trays. Each dose tray consists of a single-use 40 mg/0.8 ml prefilled syringe. Psoriasis/Uveitis Starter Package: 4 dose trays. Each dose tray consists of a single-use 40 mg/0.4 ml prefilled syringe. Single-use vial: 100 mg/10 ml Single-dose prefilled syringe: 150 mg/1.14 ml, 200 mg/1.14 ml Single-use prefilled glass syringe: 100 mg/0.67 ml Single-use vial: 250 mg/15 ml Prefilled syringe: 125 mg/1 ml Prefilled ClickJect autoinjector: 125 mg/1 ml Tablet: 30 mg Tablet, 14-day and 28-day starter kits: 10 mg, 20 mg, 30 mg Single-use vial: 100 mg/10 ml Single-use vial: 100 mg/10 ml Single-dose prefilled syringe: 210 mg/1.5 ml Single-dose prefilled SmartJect autoinjector: 50 mg/0.5 ml, 100 mg/1 ml Single-dose prefilled syringe: 50 mg/0.5 ml, 100 mg/1 ml Vial: 50 mg/4 ml (12.5 mg/ml) Single-use prefilled syringe: 45 mg/0.5 ml, 90 mg/1 ml Single-use glass vial: 45 mg/0.5 ml,90 mg/1 ml Single-dose vial for intravenous injection: 130 mg/26 ml (5 mg/ml) Single-dose prefilled autoinjector; 80 mg/ml Single-dose prefilled syringe: 80 mg/ml Single-dose prefilled syringe: 100 mg/ml Single-use vial: 300 mg/15 ml Page 22 of 26

23 (natalizumab) Xeljanz (tofacitinib) Xeljanz XR (tofacitinib) Tablet: 5 mg Tablet: 11 mg VII. References 1. Actemra Prescribing Information. South San Francisco, CA: Genentech, Inc. August Available at: Accessed September Cimzia Prescribing Information. Smyrna, GA: UCB, Inc; April Cosentyx Prescribing information. East Hanover, NJ: Novartis; January Enbrel Prescribing information. Thousand Oaks, CA: Immunex Corporation; November Available at: Accessed December 6, Entyvio Prescribing Information. Deerfield, IL: Takeda; May Humira Prescribing information. North Chicago, IL: AbbVie Inc; May October Available at: Accessed December 6, Inflectra Prescribing information. Lake Forest, IL: Hospira; April Kevzara Prescribing information. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; May Available at: Accessed November 30, Kineret Prescribing Information. Stockholm, Sweden: Swedish Orphan Biovitrum AB (publ). May Orencia Prescribing Information. New York, NY: Bristol-Myers Squibb; June Otezla Prescribing Information. San Francisco, CA: Celgene; June Remicade Prescribing information. Horsham, PA: Janssen Biotech, Inc.; October Renflexis Prescribing Information. Kenilworth, NJ: Merck & Co; April Available at: Accessed June 1, Siliq Prescribing Information. Bridgewater, NJ: Valeant Pharmaceuticals; February Available at: Accessed November 30, Simponi Prescribing information. Horsham, PA: Janssen Biotech Inc; January Simponi Aria Prescribing information. Horsham, PA: Janssen Biotech Inc; October Available at: Accessed November 27, Stelara Prescribing information. Horsham, PA: Janssen Biotech Inc; October Available at: Accessed November 27, Taltz Prescribing Information. Indianapolis, IN: Eli Lilly and Company; March Tremfya Prescribing Information. Horsham, PA: Janssen Biotech, Inc.: July Available at: Accessed November 30, Tysabri Prescribing Information. Research Triangle Park, NC: Biogen; May Xeljanz/Xeljanz XR Prescribing Information. New York, NY: Pfizer Labs. February Aletaha D, Neogi T, Silman AJ et al Rheumatoid Arthritis Classification Criteria. Arthritis and Rheumatism September 2010;62(9): Boulos P, Dougados M, MacLeod SM, et al. Pharmacological Treatment of Ankylosing Spondylitis. Drugs. 2005; 65: Page 23 of 26

24 24. Braun J, Davis J, Dougados M, et al. First update of the international ASAS consensus statement for the use of anti-tnf agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2006;65: Braun J, van den Berg R, Baraliako X, et al Update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011; 70: Colombel JF, Sandborn WJ, Rutgeerts P, et.al. Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn`s Disease: The CHARM Trial. Gastroenterology 2007;132: Lichtenstein G, Hanauer S, Sandborn W, et al. Management of Crohn`s Disease in Adults. Am J Gastroenterol 2009;104: Menter A, Gottlieb A, Feldman SR, et al. American Academy of Dermatology. Guidelines of care 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: Menter A, Gottlieb A, Feldman, SR, et al. American Academy of Dermatology. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol May 2008; 58(5): Menter A, Korman NF, Elmets ca, et al. American Academy of Dermatology. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol /j.jaad Menter A, Korman, NJ, Elmets CA, et al. American Academy of Dermatology. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60: Renflexis Drug Monograph. Clinical Pharmacology. Accessed June Ward M, Deodhar A, Akl E, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Available at Accessed July Zochling J, van der Heijde D, Burgos-Vargas, R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2006;65: Reviews, Revisions, and Approvals Date P&T Approval Date Policy converted from Actemra, Cimzia, Cosentyx, Enbrel, biologic DMARD NATL docx. Added Renflexis. Added new FDA indication for Actemra Giant Cell Arteritis. Added new FDA indication for Orencia Psoriatic Arthritis Page 24 of 26

25 Reviews, Revisions, and Approvals Date P&T Approval Date Added new FDA indication for Actemra cytokine release syndrome. Simponi Aria: Added additionally FDA-approved indications of PsA and AS; Stelara: Added FDA-approved adolescent extension of PsO indication Kevzara, Siliq, and Tremfya added to criteria. Revised redirections for contract compliance: Prefer up to two of four preferred agents (Humira, Enbrel, Cosentyx, and Otezla) where FDA-indicated, except for PsA where redirection is to both Humira and Enbrel and either Cosentyx or Otezla, and for RA where redirection is to Humira and Enbrel, then Xeljanz/Xeljanz XR, then Kevzara. Remicade is the preferred product for any IV agent where indicated. Removed off-label use of Enbrel from options for tx of HS. Humira maintenance dose for HS corrected to every week from every other week. Added Enbrel mini new dosage form. Added hyperlinked contents Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. Page 25 of 26

26 This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 26 of 26