Clinical Policy: Abatacept (Orencia) Reference Number: ERX.SPA.123 Effective Date: 10.01.16 Last Review Date: 11.17 Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description Abatacept (Orencia®) is a selective T cell co-stimulation modulator.

FDA Approved Indication(s) Orencia is indicated for:  Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA). Orencia may be used as monotherapy or concomitantly with disease- modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists  Reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). Orencia may be used as monotherapy or concomitantly with methotrexate (MTX)  Treatment of adult patients with active psoriatic arthritis (PsA)

Limitation(s) of use: Orencia should not be administered concomitantly with TNF antagonists. Orencia is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.

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 Envolve Pharmacy Solutions™ that Orencia is medically necessary when the following criteria are met:

I. Initial Approval Criteria A. Rheumatoid Arthritis (must meet all): 1. Diagnosis of RA; 2. Prescribed by or in consultation with a rheumatologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): a. Failure of a trial of MTX (at up to maximally indicated doses) used for ≥ 3 consecutive months, unless contraindicated or clinically significant adverse effects are experienced; b. If intolerance or contraindication to MTX, failure of a trial of sulfasalazine or 1 other conventional DMARD (at up to maximally indicated doses) used for ≥ 3 consecutive months, unless contraindicated or clinically significant adverse effects are experienced (see Appendix D); 5. Failure of etanercept (Enbrel is preferred) AND adalimumab (Humira is preferred), each trialed for ≥ 3 consecutive months, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization is required for etanercept and adalimumab 6. Dose does not exceed the following: a. Intravenous (IV): i. < 60 kg: 500 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; ii. 60-100 kg: 750 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; iii. > 100 kg: 1000 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; b. Subcutaneous (SC): 125 mg once weekly. Approval duration: 6 months

B. Polyarticular Juvenile Idiopathic Arthritis (must meet all):

Page 1 of 7 CLINICAL POLICY Abatacept

1. Diagnosis of active pJIA; 2. Prescribed by or in consultation with a rheumatologist; 3. Age ≥ 2 years; 4. Member meets one of the following (a or b): a. Failure of a trial of MTX used for ≥ 3 consecutive months unless contraindicated or clinically significant adverse effects are experienced; b. If intolerance or contraindication to MTX, failure of sulfasalazine or leflunomide used for ≥ 3 consecutive months unless contraindicated or clinically significant adverse effects are experienced; 5. Failure of etanercept (Enbrel is preferred) AND adalimumab (Humira is preferred), each trialed for ≥ 3 consecutive months, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization is required for etanercept and adalimumab 6. For members 2 to 5 years of age, prescribed route of administration is SC; 7. Dose does not exceed the following: a. IV: i. < 75 kg: 10 mg/kg at weeks 0, 2, and 4, then every 4 weeks thereafter; ii. ≥ 75 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; b. SC: i. 10 to <25 kg: 50 mg once weekly; ii. 25 to <50 kg: 87.5 mg once weekly; iii. ≥ 50 kg: 125 mg once weekly. Approval duration: 6 months

C. Psoriatic Arthritis (must meet all): 1. Diagnosis of active PsA; 2. Prescribed by or in consultation with a dermatologist or rheumatologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): a. Failure of a trial of MTX for ≥ 3 consecutive months unless contraindicated or clinically significant adverse effects are experienced; b. If intolerance or contraindication to MTX, failure of a trial of sulfasalazine, leflunomide, or cyclosporine for ≥ 3 consecutive months unless contraindicated or clinically significant adverse effects are experienced; 5. Failure of etanercept (Enbrel is preferred) AND adalimumab (Humira is preferred), each trialed for ≥ 3 consecutive months, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization is required for etanercept and adalimumab 6. Dose does not exceed the following: a. IV: i. < 60 kg: 500 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; ii. 60-100 kg: 750 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; iii. > 100 kg: 1000 mg at weeks 0, 2, and 4, then every 4 weeks thereafter; b. SC: 125 mg once weekly. Approval duration: 6 months

D. Other diagnoses/indications 1. Refer to ERX.PA.01 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized).

II. Continued Approval A. All Indications in Section I (must meet all): 1. Currently receiving medication via a health plan affiliated with Envolve Pharmacy Solutions or member has previously met initial approval criteria;

Page 2 of 7 CLINICAL POLICY Abatacept

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 the following: a. For RA and PsA: i. IV: a) < 60 kg: 500 mg every 4 weeks; b) 60-100 kg: 750 mg every 4 weeks; c) > 100 kg: 1000 mg every 4 weeks; ii. SC: 125 mg once weekly; b. For pJIA: i. IV: a) < 75 kg: 10 mg/kg every 4 weeks; b) ≥ 75 kg: 1000 mg every 4 weeks; ii. SC: a) 10 to <25 kg: 50 mg once weekly; b) 25 to <50 kg: 87.5 mg once weekly; c) ≥ 50 kg: 125 mg once weekly. Approval duration: 12 months

B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Envolve Pharmacy Solutions and documentation supports positive response to therapy. Approval duration: Duration of request or 6 months (whichever is less); or 2. Refer to ERX.PA.01 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 – ERX.PA.01 or evidence of coverage documents.

IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ACPA: anti-citrullinated protein antibody MTX: methotrexate ACR: American College of Rheumatology pJIA: polyarticular juvenile idiopathic arthritis CRP: C-reactive protein PsA: psoriatic arthritis DMARDs: disease-modifying antirheumatic drugs RA: rheumatoid arthritis ESR: erythrocyte sedimentation rate RF: rheumatoid factor FDA: Food and Drug Administration SC: subcutaneous IV: intravenous TNF: tumor necrosis factor

Appendix B: The 2010 ACR Classification Criteria for RA Classification criteria for RA (score-based algorithm: add score of categories A through D; a score of ≥ 6 out of 10 is needed for classification of a patient as having definite RA) Score A Joint involvement 1 large joint 0 2-10 large joints 1 1-3 small joints (with or without involvement of large joints) 2 4-10 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 protein antibody 0 (ACPA) Low positive RF or low positive ACPA 2

Page 3 of 7 CLINICAL POLICY Abatacept

Classification criteria for RA (score-based algorithm: add score of categories A through D; a score of ≥ 6 out of 10 is needed for classification of a patient as having definite RA) Score High positive RF or high positive ACPA 3 C Acute phase reactants (at least one test result is needed for classification) Normal C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR) 0 Abnormal CRP or normal ESR 1 D Duration of symptoms < 6 weeks 0 ≥ 6 weeks 1

Appendix C: Definition of MTX or DMARD Failure In RA, failure of MTX or DMARD is defined as < 50% decrease in swollen joint count, < 50% decrease in tender joint count, and < 50% decrease in ESR, or < 50% decrease in CRP.

Appendix D: Therapeutic Alternatives Drug Name Dosing Regimen Dose Limit/ Maximum Dose methotrexate Rheumatoid Arthritis Adults: 30 mg/week (Rheumatrex) 7.5 mg/week PO or 2.5 mg PO Q12 hr for 3 doses/week Children: 15 mg/m2/week

Juvenile Idiopathic Arthritis 10-15 mg/m2/week

Psoriatic Arthritis 7.5 to 15 mg/week PO sulfasalazine Rheumatoid Arthritis 5 g/day (Azulfidine) 2 gm/day PO in divided doses

Juvenile Idiopathic Arthritis 30-50 mg/kg/day PO in two divided doses

Psoriatic Arthritis 2,000 mg/day PO leflunomide Rheumatoid Arthritis 100 mg/day (Arava) 100 mg PO QD for 3 days, then 20 mg PO QD

Juvenile Idiopathic Arthritis 10-20 mg PO QD

Psoriatic Arthritis 100 mg/day PO loading dose for 3 days followed by 20 mg/day PO hydroxychloroquine Rheumatoid Arthritis 600 mg/day (Plaquenil) Initial dose: 400-600 mg/day PO Maintenance dose: 200-400 mg/day PO cyclosporine Psoriatic Arthritis 4 mg/kg/day (Sandimmune®, 2.5-3 mg/kg/day Neoral®)

Page 4 of 7 CLINICAL POLICY Abatacept

Drug Name Dosing Regimen Dose Limit/ Maximum Dose etanercept Rheumatoid Arthritis 50 mg once weekly (Enbrel, Erelzi) 50 mg SC once weekly

Juvenile Idiopathic Arthritis 0.8 mg/kg SC once weekly

Psoriatic Arthritis 25 mg SC twice weekly or 50 mg SC once weekly adalimumab Rheumatoid Arthritis Adults (Humira, 40 mg SC every other week 40 mg SC every other week for Amjevita) psoriatic arthritis, Crohn's disease, Juvenile Idiopathic Arthritis plaque psoriasis 10-40 mg SC every other week . Adolescents Psoriatic Arthritis Crohn's disease 40 mg SC every other week ≥ 40 kg: 40 mg SC every other week 17 kg to < 40 kg: 20 mg SC every other week

Children Crohn's disease ≥ 6 years and ≥ 40 kg: 40 mg SC every other week ≥ 6 years and ≥ 17 kg to < 40 kg: 20 mg SC every other week < 6 years: Safety and efficacy have not been established 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.

V. Dosage and Administration Indication Dosing Regimen Maximum Dose RA, PsA IV: IV: < 60 kg: 500 mg at weeks 0, 2, and 4, then every < 60 kg: 500 mg every 4 weeks 4 weeks thereafter 60-100 kg: 750 mg every 4 60-100 kg: 750 mg at weeks 0, 2, and 4, then weeks every 4 weeks thereafter > 100 kg: 1000 mg every 4 > 100 kg: 1000 mg at weeks 0, 2, and 4, then weeks every 4 weeks thereafter SC: SC: 125 mg/week 125 mg once weekly pJIA IV: IV: < 75 kg: 10 mg/kg at weeks 0, 2, and 4, then < 75 kg: 10 mg/kg every 4 every 4 weeks thereafter weeks 75 to 100 kg: 750 mg at weeks 0, 2, and 4, then 75 to 100 kg: 750 mg every 4 every 4 weeks thereafter weeks >100 kg: 1000 mg at weeks 0, 2, and 4, then > 100 kg: 1000 mg every 4 every 4 weeks thereafter weeks

SC: SC: 10 to <25 kg: 50 mg once weekly 10 to <25 kg: 50 mg/week

Page 5 of 7 CLINICAL POLICY Abatacept

Indication Dosing Regimen Maximum Dose 25 to <50 kg: 87.5 mg once weekly 25 to <50 kg: 87.5 mg/week ≥ 50 kg: 125 mg once weekly ≥ 50 kg: 125 mg/week

VI. Product Availability  Single-use vial for IV infusion: 250 mg  Single-dose prefilled syringes for SC injection: 50 mg/0.4 mL, 87.5 mg/0.7 mL, 125 mg/mL  Single-dose prefilled ClickJect autoinjector for SC injection: 125 mg/mL

VII. References 1. Orencia Prescribing Information. Princeton, NJ: Bristol-Meyers Squibb Company; June 2017. Available at: http://www.orenciahcp.com/. Accessed September 29, 2017. 2. Enbrel Prescribing Information. Thousand Oaks, CA: Amgen Inc.; November 2016. Available at: https://www.enbrel.com/. Accessed July 2017. 3. Humira Prescribing Information. North Chicago, IL: AbbVie Inc.; April 2017. Available at: https://www.humira.com/. Accessed July 2017. 4. Ringold, S., Weiss, P. F., Beukelman, T., DeWitt, E. M., Ilowite, N. T., Kimura, Y., Laxer, R. M., Lovell, D. J., Nigrovic, P. A., Robinson, A. B. and Vehe, R. K. (2013), 2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for the Medical Therapy of Children With Systemic Juvenile Idiopathic Arthritis and Tuberculosis Screening Among Children Receiving Biologic Medications. Arthritis & Rheumatism, 65: 2499–2512. 5. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Rheumatology 2016. 68(1):1-26. 6. Aletaha D, Neogi T, Silman AJ et al. 2010 Rheumatoid Arthritis Classification Criteria. Arthritis and Rheumatism September 2010;62(9):2569-2581.

Reviews, Revisions, and Approvals Date P&T Approval Date Policy split from USS.SPMN.44 Rheumatoid Arthritis and Ankylosing 08.16 09.16 Spondylitis Treatments and converted to new template. Removed all safety criteria. Added weight range-based dosing for each indication per PI. Modified criteria to require trial of other biologic for the indication or methotrexate, unless contraindicated; added sulfasalazine as an alternative to methotrexate if methotrexate is contraindicated; added preferencing for Enbrel & Humira. RA: added age requirement per PI. pJIA: removed question related to number of affected joints as development of arthritis in > 4 joints is required for the diagnosis. Converted to new template. 07.17 08.17 pJIA: per label updated max dosing, revised age restriction down to 2 years, and clarified SC use for age 2 to 5 PsA: added new FDA approved indication RA: Revised criteria for confirmation of RA diagnosis per 2010 ACR Criteria. 4Q17 Annual Review 09.29.17 11.17 -RA: removed requirement for submission of diagnostic lab since a specialist is required to prescribe or be consulted -PsA: changed requirement of hydroxychloroquine to cyclosporine for PsA per 3Q17 PsA TCR and AAD guidelines

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;

Page 6 of 7 CLINICAL POLICY Abatacept 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.

This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. 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 policy is the property of Envolve Pharmacy Solutions. Unauthorized copying, use, and distribution of this Policy or any information contained herein is strictly prohibited. By accessing this policy, you agree to be bound by the foregoing terms and conditions, in addition to the Site Use Agreement for Health Plans associated with Envolve Pharmacy Solutions.

©2016 Envolve Pharmacy Solutions. All rights reserved. All materials are exclusively owned by Envolve Pharmacy Solutions 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 Envolve Pharmacy Solutions. You may not alter or remove any trademark, copyright or other notice contained herein.

Page 7 of 7