Subject: Abatacept (Orencia ) Injection and Infusion

Transcription

1 09-J Original Effective Date: 06/15/07 Reviewed: 09/12/18 Revised: 10/15/18 Subject: Abatacept (Orencia ) Injectin and Infusin THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION. Dsage/ Administratin Psitin Statement Billing/Cding Reimbursement Prgram Exceptins Definitins Related Guidelines Other References Updates DESCRIPTION: Abatacept (Orencia), a mdulatr f T-lymphcyte activatin, was first apprved as an intravenus (IV) infusin by the US Fd and Drug Administratin (FDA) in December 2005 fr adult rheumatid arthritis (RA) and then in April 2008 fr plyarticular juvenile idipathic arthritis (JIA) in pediatric patients 6 years f age and lder. In July 2011, a subcutaneus (SQ) injectin was apprved fr the treatment f RA. In March 2017, the FDA-apprved indicatin fr the SQ injectin was expanded t include the treatment f JIA in pediatric patients 2 years f age and lder. Abatacept (as spnsred by the innvatr drug cmpany) has been granted rphan drug designatin by the FDA fr treatment f idipathic inflammatry mypathy (IMM) in February 2017 and treatment f giant cell arteritis in February Abatacept s mechanism f actin is distinct frm the available nn-bilgical disease-mdifying antirheumatic drugs (DMARDs) and ther bilgics (e.g., tumr necrsis factr antagnists [TNFs], interleukin antagnists). Abatacept is a human prtein designed t selectively inhibit T-cell activatin, a prcess that plays a central rle in the immunpathgenesis f RA. It exerts this mechanism f actin by binding t the natural ligands CD80 and CD86, ultimately preventing CD80 and CD86 interactin with CD28 n the T-lymphcyte. Additinally, abatacept indirectly inhibits the prductin f inflammatry cytkines and aut-antibdies, which are als hypthesized t play a rle in the pathgenesis f RA. In 2015, the American Cllege f Rheumatlgy (ACR) published an updated guideline fr the treatment f RA. The next update t the guideline is expected in late 2019 r early The guidelines supprt

2 the use f a nn-tnf bilgic (e.g., abatacept) in the fllwing scenaris: (1) patients with early RA if disease activity remains mderate r high despite DMARD mntherapy (with r withut gluccrticids), use cmbinatin DMARDS r a TNFi r a nn-tnf bilgic (all chices with r withut methtrexate (MTX), in n particular rder f preference); (2) patients with established RA if disease activity remains mderate r high despite DMARD mntherapy, use cmbinatin traditinal DMARDS r add a TNFi r a nn-tnf bilgic r tfacitinib (all chices with r withut MTX, in n particular rder f preference); (3) patients with established RA if disease activity remains mderate r high despite use f a single TNFi, use a nn-tnf bilgic, with r withut MTX; (4) patients with established RA if disease activity remains mderate r high despite use f a single nn-tnf bilgic, use anther nn-tnf bilgic, with r withut MTX; (5) patients with established RA if disease activity remains mderate r high despite use f multiple (2+) sequential TNFi therapies, first use a nn-tnf bilgic, with r withut MTX; and (6) patients with established RA if disease activity remains mderate r high despite use f at least ne TNFi and at least ne nn-tnf bilgic, first use anther nn-tnf bilgic, with r withut MTX. Nn-TNF bilgics are als recmmended when patients must avid a TNFi due t certain high-risk cnditins [i.e., cngestive heart failure, lymphprliferative disrders, and previus serius infectin (abatacept nly)]. While the fllwing studies d nt include abatacept, they supprt the use f cmbinatin DMARD therapy as a valid ptin fr patients with established mderate t severe RA. In the 2015 TACIT pragmatic, nn-inferirity, randmized cntrlled trial, 205 persns with established mderate t severe RA received either an anti-tnf bilgic with ne DMARD (e.g., methtrexate), r cnventinal DMARD therapy titrated upward t include cmbinatin therapy. Mst persns in the DMARD grup eventually received 2 r 3 DMARDs in cmbinatin (e.g., methtrexate + leflunmide). The DMARD grup was shwn t be nn-inferir t the anti-tnf grup fr the primary utcme f disability measured by a patient-recrded health assessment questinnaire at 12 mnths with a numerical advantage twards the DMARD grup. Further supprting use f cmbinatin DMARD therapy, the 2- year fllw-up f the SWEFOT trial (438 persns with methtrexate-refractry RA) shwed n difference in utility r QALY gain ver 21 mnths when cmparing methtrexate + infliximab vs. methtrexate + sulfasalazine + hydrxychlrquine. While methtrexate must be avided in wmen wh are pregnant r trying t becme pregnant, sulfasalazine has adequate data supprting safe use (pregnancy Categry B), and is cnsider a preferred DMARD when given with flic acid if treatment is clinically necessary. Hydrxychlrquine, cyclsprine, and anti-tnf bilgics are als cnsidered t be lw-risk ptins during pregnancy. POSITION STATEMENT: Cmparative Effectiveness The Fd and Drug Administratin has deemed the drug(s) r bilgical prduct(s) in this cverage plicy t be apprpriate fr self-administratin r administratin by a caregiver (i.e., nt a healthcare prfessinal). Therefre, cverage (i.e., administratin) f the subcutaneus frmulatin f abatacept in a prvider-administered setting such as an utpatient hspital, ambulatry surgical suite, physician

3 ffice, r emergency facility is nt cnsidered medically necessary. This statement des nt apply t the intravenus (IV) frmulatin f abatacept. NOTE: The preferred self-administered bilgic prducts fr certain indicatins are: Axial spndylarthritis - adalimumab (Humira), etanercept (Enbrel), glimumab (Simpni), and secukinumab (Csentyx) Crhn s disease - adalimumab (Humira) and ustekinumab (Stelara) Hidradenitis suppurativa - adalimumab (Humira) Plaque psriasis - adalimumab (Humira), etanercept (Enbrel), secukinumab (Csentyx), and ustekinumab (Stelara) Plyarticular juvenile idipathic arthritis - adalimumab (Humira) and etanercept (Enbrel), Psriatic arthritis - adalimumab (Humira), etanercept (Enbrel), glimumab (Simpni), secukinumab (Csentyx), and ustekinumab (Stelara) Rheumatid arthritis - adalimumab (Humira), etanercept (Enbrel), and glimumab (Simpni) Ulcerative clitis - adalimumab (Humira) and glimumab (Simpni) Uveitis - adalimumab (Humira) Initiatin f abatacept (Orencia) meets the definitin f medical necessity when BOTH f the fllwing are met: 1. Abatacept is administered fr an indicatin listed in Table 1 and ALL f the indicatin-specific and maximum-allwable dse criteria are met 2. Abatacept is NOT used in cmbinatin with ANY f the fllwing: a. adalimumab (Humira) b. anakinra (Kineret) c. apremilast (Otezla) d. baricitinib (Olumiant) e. brdalumab (Siliq) f. certlizumab (Cimzia) g. etanercept (Enbrel) h. glimumab (Simpni, Simpni Aria) i. guselkumab (Tremfya) j. infliximab prducts (Remicade, Inflectra, Renflexis) k. ixekizumab (Taltz) l. sarilumab (Kevzara)

4 m. secukinumab (Csentyx) n. tildrakizumab-asmn (Ilumya). tcilizumab (Actemra) p. tfacitinib (Xeljanz, Xeljanz XR) q. ustekinumab (Stelara) r. vedlizumab (Entyvi) Table 1 Indicatins and Specific Criteria Indicatin Specific Criteria Maximum Allwable Dse Plyarticular juvenile idipathic arthritis (PJIA) [previusly knwn as plyarticular juvenile rheumatid arthritis (PJRA)] When ALL f the fllwing are met ( 1, 2, 3, and 4 ): 1. EITHER f the fllwing: a. Fr SQ use: member is 2 years f age r lder b. Fr IV use: member is 6 years f age r lder 2. Member s disease is mderately t severely active 3. Member has had an inadequate respnse t, r has a cntraindicatin t ONE r mre csdmards* (e.g., methtrexate, sulfasalazine, cyclsprine, leflunmide) (the specific cntraindicatin must be prvided) 4. Member has had an inadequate respnse, persistent and intlerable adverse effects, r a cntraindicatin t BOTH f the fllwing self-administered bilgics (the specific adverse effects and/r cntraindicatins must be prvided) adalimumab (Humira) etanercept (Enbrel) Intravenus infusin Initial dse: >100 kg: 1,000 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) 75 t 100 kg: 750 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) <75 kg: 10 mg/kg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) Maintenance: >100 kg: 1,000 mg every 4 weeks starting at week 8 75 t 100 kg: 750 mg every 4 weeks starting at week 8 <75 kg: 10 mg/kg every 4 weeks starting at week 8 Subcutaneus injectin: 10 t <25 kg: 50 mg every week 25 t <50 kg: 87.5 mg every week

5 Psriatic arthritis (PsA) [including bth axial and nn-axial (peripheral) PsA] ALL f the fllwing ( 1, 2, 3, and 4 ): 1. Member is 18 years f age r lder 2. Member s disease is active (i.e., persistent jint inflammatin) 3. EITHER f the fllwing based n the dminate disease type* ( a r b ): a. Axial PsA: Member has had an inadequate respnse t, r has a cntraindicatin t at least TWO different NSAID therapies taken cntinuusly fr at least 4 weeks each (e.g., celecxib, diclfenac, ibuprfen, melxicam, naprxen) (the specific cntraindicatins must be prvided) b. Peripheral PsA: Member has had an inadequate respnse t, r has a cntraindicatin t at least ONE NSAID therapy taken cntinuusly fr at least 4 weeks (e.g., celecxib, diclfenac, ibuprfen, melxicam, naprxen) (the specific cntraindicatin must be prvided) AND Member has had an inadequate respnse t, r has a cntraindicatin t methtrexate at the maximally tlerated dsage (e.g., methtrexate titrated t 25 mg weekly), r, if methtrexate is cntraindicated, t anther csdmard (e.g., cyclsprine, leflunmide, sulfasalazine) (the specific cntraindicatin must be prvided) 4. EITHER f the fllwing ( a r b ): a. Member has had an inadequate respnse, has persistent and intlerable adverse effect(s), r has a cntraindicatin t THREE r mre f the fllwing self-administered bilgic therapies (the specific adverse effect(s) and/r cntraindicatins must be prvided): etanercept (Enbrel) adalimumab (Humira) 50 kg: 125 mg every week Intravenus infusin Initial: >100 kg: 1,000 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) 60 t 100 kg: 750 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) <60 kg: 500 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) Maintenance: >100 kg: 1,000 mg every 4 weeks starting at week 8 60 t 100 kg: 750 mg every 4 weeks starting at week 8 <60 kg: 500 mg every 4 weeks starting at week 8 Subcutaneus injectin: 125 mg every week

6 Rheumatid arthritis (RA) glimumab (Simpni) secukinumab (Csentyx) ustekinumab (Stelara) b. BOTH f the fllwing ( i and ii ): i. Member has had an inadequate respnse t, has persistent and intlerable adverse effects, r has a cntraindicatin t BOTH ustekinumab (Stelara) and secukinumab (Csentyx) (the specific adverse effect and/r cntraindicatin must be prvided) ii. Member shuld cnsider alternatives t the use f an anti- TNF bilgic due t a prduct warning and precautin fr ANY f the fllwing (the specific cnditin must be prvided): Demyelinating disease (e.g., multiple sclersis) Serius, chrnic r recurrent infectins (the specific infectin and duratin/frequency f illness must be prvided) Previusly treated lymphprliferative disrder (e.g., leukemias, lymphmas) # Current r wrsening cngestive heart failure # The 2015 ACR guideline gives the use f rituximab ver a TNFi a strng recmmendatin, while the use f abatacept ver a TNFi is a cnditinal recmmendatin When ALL f the fllwing are met ( 1, 2, 3, 4, and 5 ): 1. Member is 18 years f age r lder 2. Member s disease is mderately t severely active 3. Member has had an inadequate respnse (i.e., unable t achieve remissin r lw Intravenus infusin Initial: >100 kg: 1,000 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) 60 t 100 kg: 750 mg every 2 weeks fr 3

7 disease activity) t at least three cntinuus mnths f therapy with at least TWO csdmards (e.g., hydrxychlrquine, methtrexate, sulfasalazine, leflunmide) used in cmbinatin at the maximally tlerated dsage (e.g., methtrexate titrated t 25 mg weekly). A trial f csdmard mntherapy at the maximally tlerated dsage fr at least three cntinuus mnths is sufficient if member has a cntraindicatin t BOTH methtrexate AND either sulfasalazine r hydrxychlrquine* (the specific cntraindicatins must be prvided; pregnancy is nt cnsidered a cntraindicatin t the use f sulfasalazine r hydrxychlrquine) 4. EITHER f the fllwing ( a r b ): a. Member has had an inadequate respnse t, has persistent and intlerable adverse effect(s), r has a cntraindicatin t TWO r mre f the fllwing self-administered bilgic therapies (the specific adverse effect(s) and/r cntraindicatins must be prvided): etanercept (Enbrel) adalimumab (Humira) glimumab (Simpni) b. Member shuld cnsider alternatives t the use f an anti-tnf bilgic due t a prduct warning and precautin fr ANY f the fllwing (the specific cnditin must be prvided): Demyelinating disease (e.g., multiple sclersis) Serius, chrnic r recurrent infectins (the specific infectin and duratin/frequency f illness must be prvided) Previusly treated lymphprliferative disrder (e.g., leukemias, lymphmas) # Current r wrsening cngestive heart failure ttal dses (week 0, 2, and 4) <60 kg: 500 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) Maintenance: >100 kg: 1,000 mg every 4 weeks starting at week 8 60 t 100 kg: 750 mg every 4 weeks starting at week 8 <60 kg: 500 mg every 4 weeks starting at week 8 Subcutaneus injectin: 125 mg every week

8 Orphan Indicatins Giant cell arteritis (GCA) Idipathic inflammatry mypathy (IMM) [includes dermatmysitis (DM) and plymysitis (PM)] # The 2015 ACR guideline gives the use f rituximab ver a TNFi a strng recmmendatin, while the use f abatacept ver a TNFi is a cnditinal recmmendatin 5. Member has had an inadequate respnse, persistent and intlerable adverse effects, r a cntraindicatin t treatment with tfacitinib (Xeljanz, Xeljanz XR) (the specific adverse effects and/r cntraindicatins must be prvided) When ALL f the fllwing are met ( 1, 2, 3. and 4 ): 1. Member has active disease as defined by BOTH f the fllwing ( a and b ): a. Presence f cranial symptms, OR symptms f plymyalgia rheumatica b. ESR 30 mm/hr, OR CRP 1 mg/dl 2. Member is currently receiving crticsterid treatment fr their GCA 3. One gal f treatment is t reduce the current daily dse f the crticsterid 4. Member is 18 years f age r lder When BOTH f the fllwing are met ( 1 and 2 ): 1. The members diagnsis has been cnfirmed by muscle bipsy 2. The member disease is refractry t at least 3 mnths f cntinuus cmbinatin treatment with a crticsterid and an ntravenus infusin Initial: >100 kg: 1,000 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) 60 t 100 kg: 750 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) <60 kg: 500 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) Maintenance: >100 kg: 1,000 mg every 4 weeks starting at week 8 60 t 100 kg: 750 mg every 4 weeks starting at week 8 <60 kg: 500 mg every 4 weeks starting at week 8 Subcutaneus injectin: 125 mg every week Intravenus infusin Initial: >100 kg: 1,000 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) 60 t 100 kg: 750 mg every 2 weeks fr 3

9 Preventin f Graft versus Hst Disease (GVHD) Apprval duratin: 6 mnths immunsuppressant (either azathiprine r methtrexate) When BOTH f the fllwing are met ( 1 and 2 ): 1. Member will receive an allgenic HSCT the day fllwing the first dse 2. The use f cnventinal treatment with methtrexate and a calcineurin inhibitr needs t be avided ttal dses (week 0, 2, and 4) <60 kg: 500 mg every 2 weeks fr 3 ttal dses (week 0, 2, and 4) Maintenance: >100 kg: 1,000 mg every 4 weeks starting at week 8 60 t 100 kg: 750 mg every 4 weeks starting at week 8 <60 kg: 500 mg every 4 weeks starting at week 8 Subcutaneus injectin: 125 mg every week Nt t exceed the FDAapprved maximum dsage NSAID, nn-steridal anti-inflammatry; SQ, subcutaneusly; BSA, bdy surface area; csdmard, cnventinal synthetic disease mdifying anti-rheumatic drug *NOTE: If the member has had an inadequate respnse t previus bilgic therapy, ther than abatacept, that is FDA-apprved fr the requested indicatin listed in Table 1, the member is NOT required t have had an inadequate respnse t nn-bilgic prerequisite therapy (e.g., fr RA, if member has previusly had an inadequate respnse t etancercept, but des nt have a histry f inadequate respnse t cmbinatin csdmards, they d nt have t try tw csdmards in cmbinatin t meet medical necessity criteria). Hwever, members must still meet the preferred self-administered (i.e., subcutaneus) bilgic prduct requirement and the tfacitinib requirement (if the use is fr RA). NOTE: Members initiated and maintained n IV abatacept therapy (i.e., submitted as a medical claim with J0129) are NOT required t have had an inadequate respnse t the preferred self-administered (i.e., subcutaneus) bilgic prducts r tfacitinib (Xeljanz, Xeljanz XR). Hwever, members transitining t the subcutaneus frmulatin after an initial IV dse must still meet the preferred selfadministered bilgic prduct requirement and tfacitinib requirement (if use is fr RA). Cntinuatin f abatacept meets the definitin f medical necessity when ALL f the fllwing criteria are met: 1. Member has demnstrated a beneficial clinical respnse with abatacept therapy

10 2. An authrizatin r reauthrizatin fr abatacept has been previusly apprved by Flrida Blue r anther health plan in the past 2 years fr the treatment f a cnditin in Table 1 (except preventin f GVHD - see intiatin criteria), OR the member previusly met ALL indicatin-specific initiatin criteria 3. Abatacept is NOT used in cmbinatin with ANY f the fllwing: a. adalimumab (Humira) b. anakinra (Kineret) c. apremilast (Otezla) d. baricitinib (Olumiant) e. brdalumab (Siliq) f. certlizumab (Cimzia) g. etanercept (Enbrel) h. glimumab (Simpni, Simpni Aria) i. guselkumab (Tremfya) j. infliximab prducts (Remicade, Inflectra, Renflexis) k. ixekizumab (Taltz) l. sarilumab (Kevzara) m. secukinumab (Csentyx) n. tildrakizumab-asmn (Ilumya). tcilizumab (Actemra) p. tfacitinib (Xeljanz, Xeljanz XR) q. ustekinumab (Stelara) r. vedlizumab (Entyvi) 4. The member s dsage des nt exceed the fllwing based n their weight and indicatin fr use: Rheumatid arthritis, psriatic arthritis, GCA, and IMM PJIA Intravenus infusin >100 kg: 1,000 mg every 4 weeks 60 t 100 kg: 750 mg every 4 weeks <60 kg: 500 mg every 4 weeks Subcutaneus injectin 125 mg every week Intravenus infusin (age 6 year r lder)

11 Apprval Duratin: 1 year >100 kg: 1,000 mg every 4 weeks 75 t 100 kg: 750 mg every 4 weeks <75 kg: 10 mg/kg every 4 weeks Subcutaneus injectin (age 2 years r lder) 10 t <25 kg: 50 mg every week 25 t <50 kg: 87.5 mg every week 50 kg: 125 mg every week DOSAGE/ADMINISTRATION: THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE. FDA-apprved: abatacept is indicated fr treatment f the fllwing indicatins Fr reducing signs and symptms, inducing majr clinical respnse, inhibiting the prgressin f structural damage, and imprving physical functin in adult patients with mderately t severely active rheumatid arthritis in adults, as mntherapy r cncmitantly with disease-mdifying antirheumatic drugs (DMARDs) ther than tumr-necrsis factr (TNF) antagnists Fr reducing signs and symptms in patients 2 years f age and lder with mderately t severely active plyarticular juvenile idipathic arthritis, as mntherapy r in cmbinatin with methtrexate Fr the treatment f adult patients with active psriatic arthritis (PsA) ADULT RHEUMATOID ARTHRITIS Abatacept is administered as an intravenus (IV) r subcutaneus (SQ) injectin. IV infusins shuld be administered as a 30-minute infusin utilizing weight range-based dsing specified in Table 2. Fllwing the initial IV administratin, an IV infusin shuld be administered at 2 and 4 weeks after the first infusin and every 4 weeks thereafter. Table 2 Table 2: Abatacept IV dse in adult RA persns Bdy weight Dse Number f vials Less than 60 kg 500 mg 2

12 60 t 100 kg 750 mg 3 Mre than 100 kg 1,000 mg 4 Each vial prvides 250 mg f abatacept fr administratin Fllwing a single IV lading dse (as per bdy weight categries listed in Table 1), the first 125 mg SQ injectin f abatacept shuld be given within a day, fllwed by 125 mg SQ injectins nce weekly. Persns unable t receive an infusin may initiate weekly injectins f SQ abatacept withut an IV lading dse Persns transitining frm abatacept IV therapy t SQ administratin shuld administer the first SQ dse instead f the next scheduled IV dse. JUVENILE IDIOPATHIC ARTHRITIS The recmmended intravenus dsage fr persns aged 6 t 17 years f age: Less than 75 kg: 10 mg/kg IV n week 0, 2, 4, and every 4 weeks thereafter Greater than 75 kg: use adult IV dsing regimen, nt t exceed a maximum dse f 1,000 mg Intravenus dsing has nt been studied in patients yunger than 6 years f age The recmmended subcutaneus dsage fr persns aged 2 t 17 years f age: 10 t less than 25 kg: 50 kg nce weekly 25 t less than 50 kg: 87.5 mg nce weekly 50 kg r mre: 125 mg nce weekly ADULT PSORIATIC ARTHRITIS Abatacept is administered as an intravenus (IV) r subcutaneus (SQ) injectin with r withut nnbilgical DMARDs. IV infusins shuld be administered as a 30-minute infusin utilizing weight range-based dsing specified in Table 2. Fllwing the initial IV administratin, an IV infusin shuld be administered at 2 and 4 weeks after the first infusin and every 4 weeks thereafter. The SQ injectins administered nce weekly withut the need fr an IV lading dse. Persns transitining frm abatacept IV therapy t SQ administratin shuld administer the first SQ dse instead f the next scheduled IV dse. Drug Availability: Intravenus infusin: 250 mg lyphilized pwder in a single use vial Subcutaneus injectin:

13 50 mg/0.4 ml, 87.5 mg/0.7 ml, and 125 mg/ml single-dse prefilled glass syringes 125 mg/ml slutin in a single-dse prefilled autinjectr (ClickJect) PRECAUTIONS: Bxed Warning Nne Cntraindicatins Nne Warnings: Cncmitant Use with TNF Antagnists: cncmitant use with a TNF antagnist can increase the risk f infectins and serius infectins. Hypersensitivity: hypersensitivity, anaphylaxis, and anaphylactid reactins have ccurred fllwing abatacept administratin. Infectins: persns with a histry f recurrent infectins r underlying cnditins predispsing t infectins may experience mre infectins; discntinue if a serius infectin ccurs. Tuberculsis: screen fr latent TB infectin prir t initiating therapy. Members testing psitive shuld be treated prir t initiating abatacept. Immunizatins: live vaccines shuld nt be given cncurrently r within three mnths f discntinuatin. Members with juvenile idipathic arthritis shuld be brught up t date with all immunizatins prir t abatacept therapy. Abatacept may blunt the effectiveness f sme immunizatins based n its mechanism f actin. Chrnic Obstructive Pulmnary Disease (COPD): Persns with COPD may develp mre frequent respiratry events. BILLING/CODING INFORMATION: The fllwing cdes may be used t describe: HCPCS Cding: J0129 Injectin, abatacept, 10mg ICD-10 Diagnsis Cdes That Supprt Medical Necessity: D D Graft-versus-hst disease

14 L40.50 Arthrpathic psriasis, unspecified L40.51 Distal interphalangeal psriatic arthrpathy L40.52 Psriatic arthritis mutilans L40.53 Psriatic spndylitis L40.59 Other psriatic arthrpathy M05.00 M05.09 Felty's syndrme M05.10 M05.19 Rheumatid lung disease with rheumatid arthritis M05.20 M05.29 Rheumatid vasculitis with rheumatid arthritis M05.30 M05.39 Rheumatid heart disease with rheumatid arthritis M05.40 M05.49 Rheumatid mypathy with rheumatid arthritis M05.50 M05.59 Rheumatid plyneurpathy with rheumatid arthritis M05.60 M05.69 Rheumatid arthritis with invlvement f ther rgans and systems M05.70 M05.79 Rheumatid arthritis with rheumatid factr withut rgan r systems invlvement M05.80 M05.89 Other rheumatid arthritis with rheumatid factr M05.9 Rheumatid arthritis with rheumatid factr, unspecified M06.00 M06.09 Rheumatid arthritis withut rheumatid factr M06.20 M06.29 Rheumatid bursitis M06.30 M06.39 Rheumatid ndule M06.80 M06.89 Other specified rheumatid arthritis

15 M06.9 Rheumatid arthritis, unspecified M08.09 Unspecified juvenile rheumatid arthritis, multiple sites M08.3 Juvenile rheumatid plyarthritis (sernegative) M08.89 Other juvenile arthritis, multiple sites M31.5 Giant cell arteritis with plymyalgia rheumatica M31.6 Other giant cell arteritis M33.00 M33.09 Juvenile dermatplymysitis M33.10 M33.19 Other dermatplymysitis M33.20 M33.29 Plymysitis M33.90 M33.99 Dermatplymysitis, unspecified REIMBURSEMENT INFORMATION: Refer t sectin entitled POSITION STATEMENT. PROGRAM EXCEPTIONS: Federal Emplyee Prgram (FEP): Fllw FEP guidelines. State Accunt Organizatin (SAO): Fllw SAO guidelines. Medicare Advantage prducts: N Natinal Cverage Determinatin (NCD) was fund at the time f the last guideline review date. The fllwing Lcal Cverage Determinatin (LCD) was reviewed n the last guideline review date: Abatacept (L33257) lcated at fcs.cm. Medicare Part D: Flrida Blue has delegated t Prime Therapeutics authrity t make cverage determinatins fr the Medicare Part D services referenced in this guideline. DEFINITIONS: Axial PsA (a.k.a., psriatic spndylitis): a subset f psriatic arthritis that affects the spine (i.e., spndylitis) and/r spinal jints (e.g., the sacriliac jint between the sacrum and ilium f pelvis). Axial PsA shares similar clinical findings t patients with ankylsing spndylitis (AS); hwever, patients with axial PsA are ften less symptmatic, have asymmetric disease, and tend t have less severe disease. In

16 additin, the psriatic plaques r nail changes present in patients with axial PsA are absent in patients with AS. Abut 5% f PsA patients have exclusively axial invlvement, and 20 t 50% have bth spinal and peripheral invlvement, with peripheral jint invlvement being the predminant pattern. DMARD: An acrnym fr disease-mdifying antirheumatic drug. These are drugs that mdify the rheumatic disease prcesses, and slw r inhibit structural damage t cartilage and bne. These drugs are unlike symptmatic treatments such as NSAIDs that d nt alter disease prgressin. DMARDs can be further subcategrized. With the release f bilgic agents (e.g., anti-tnf drugs), DMARDs were divided int either: (1) cnventinal, traditinal, synthetic, r nn-bilgical DMARDs; r as (2) bilgical DMARDs. Hwever, with the release f newer targeted nn-bilgic drugs and bisimilars, DMARDs are nw best categrized as: (1) cnventinal synthetic DMARDs (csdmard) (e.g., MTX, sulfasalazine), (2) targeted synthetic DMARDs (tsdmard) (e.g., apremilast, baricitinib, tfacitinib), and (3) bilgical DMARDs (bdmard), which can be either a bisimilar DMARD (bsdmard) r bilgical riginatr DMARD (bdmard). Nn-axial r peripheral PsA: a subset f psriatic arthritis that des NOT affect the spine r spinal jints [e.g. elbw, wrist, knees, hands, feet, and digits (dactylitis)]. Peripheral invlvement may be plyarticular (5 r mre jints affected) r ligarticular (a.k.a., pauciarticular) (4 r fewer jints affected). Apprximately 95% f patients with PsA have invlvement f the peripheral jints, predminantly the plyarticular frm, whereas a minrity have the ligarticular frm. Psriatic arthritis (PsA): jint inflammatin that ccurs in abut 5% t 10% f peple with psriasis (a cmmn skin disrder). It is a severe frm f arthritis accmpanied by inflammatin, psriasis f the skin r nails, and a negative test fr rheumatid factr. Enthesitis refers t inflammatin f entheses, the site where ligaments r tendns insert int the bnes. It is a distinctive feature f PsA and des nt ccur with ther frms f arthritis. Cmmn lcatins fr enthesitis include the bttms f the feet, the Achilles' tendns, and the places where ligaments attach t the ribs, spine, and pelvis. Rheumatid arthritis: An inflammatry disease f the synvium, r lining f the jint that results in pain stiffness, and swelling f multiple jints. The inflammatin may extend t ther jints and cause bne and cartilage ersin, jint defrmities, mvement prblems, and activity limitatins. RELATED GUIDELINES: Adalimumab (Humira), 09-J Anakinra (Kineret), 09-J Apremilast (Otezla) Tablet, 09-J Certlizumab Pegl (Cimzia), 09-J Etanercept (Enbrel), 09-J Glimumab (Simpni, Simpni Aria ), 09-J

17 Infliximab Prducts [infliximab (Remicade), infliximab-dyyb (Inflectra), and infliximab-abda (Renflexis)], 09-J Rituximab (Rituxan), 09-J Sarilumab (Kevzara), 09-J Tcilizumab (Actemra) Injectin, 09-J Tfacitinib (Xeljanz, Xeljanz XR) Tablets, 09-J OTHER: Table 2: Cnventinal Synthetic DMARDs Generic Name Brand Name Auranfin (ral gld) Azathiprine Cyclsprine Hydrxychlrquine Leflunmide Methtrexate Sulfasalazine Ridaura Imuran Neral, Sandimmune Plaquenil Arava Rheumatrex, Trexall Azulfidine, Azulfidine EN-Tabs Table 3: Grading f Severity f Rheumatid Arthritis Severity Mild Mderate Criteria Jint pain Inflammatin f at least 3 jints N inflammatin in tissues ther than the jints Usually, a negative result n a rheumatid factr test An elevated erythrcyte sedimentatin rate (ESR) r C reactive prtein (CRP) level N evidence f bne r cartilage damage n x-rays Between 6 and 20 inflamed jints

18 Usually n inflammatin in tissues ther than the jints An elevated ESR r CRP levels A psitive rheumatid factr test r anti-cyclic citrullinated peptide (anti-ccp) antibdies Evidence f inflammatin but n evidence f bne damage n x-rays Severe Mre than 20 persistently inflamed jints r a rapid lss f functinal abilities Elevated ESR r CRP levels Anemia related t chrnic illness Lw bld albumin level A psitive rheumatid factr test, ften with a high level Evidence f bne and cartilage damage n x-ray Inflammatin in tissues ther than jints REFERENCES: 1. Bansback N, Phibbs CS, Sun H1, et al; CSP 551 RACAT Investigatrs.Triple Therapy Versus Bilgic Therapy fr Active Rheumatid Arthritis: A Cst-Effectiveness Analysis. Ann Intern Med Jul 4;167(1): Beukelman T, Atkar NM, Saag KG, et al American Cllege f Rheumatlgy Recmmendatins fr the treatment f juvenile idipathic arthritis: initiatin and safety mnitring f therapeutic agents fr the treatment f arthritis and systemic features. Arthritis Care Res 2011;63(4): Clinical Pharmaclgy [database nline]. Tampa, FL: Gld Standard, Inc.; Available at: Accessed 8/28/ Cates LC, Kavanaugh A, Mease PJ et al. Grup fr Research and Assessment f Psriasis and Psriatic Arthritis: Treatment Recmmendatins fr Psriatic Arthritis Arthritis Rheumatl 2016;68: FDA Orphan Drug Designatins and Apprvals [Internet]. Washingtn, D.C. [cited 2018 August 28]. Available frm: 6. Genant HK, Peterfy CG, Westhvens R, Becker JC, Aranda R, Vratsans G, Teng J, Kremer JM. Abatacept inhibits structural damage prgressin in rheumatid arthritis: results frm the lng-term extensin f the AIM trial. Ann Rheum Dis Dec Genvese MC, Schiff M, Luggen M, et al. Lngterm safety and efficacy f abatacept thrugh 5 years f treatment in patients with rheumatid arthritis and an inadequate respnse t tumr necrsis factr inhibitr therapy. J Rheumatl Aug;39(8): Gttlieb A, Krman NJ, Grdn KB, et al. Guidelines f care fr the management f psriasis and psriatic arthritis: Sectin 2. Psriatic arthritis: verview and guidelines f care fr treatment with an emphasis n the bilgics. J Am Acad Dermatl May;58(5): di: /j.jaad Graudal N, Hubeck-Graudal T, Tarp S, et al. Effect f cmbinatin therapy n jint destructin in rheumatid arthritis: a netwrk meta-analysis f randmized cntrlled trials. PLS One Sep 22;9(9):e Karlssn JA, Nevius M, Nilssn JA, et al. Additin f infliximab cmpared with additin f sulfasalazine and hydrxychlrquine t methtrexate in early rheumatid arthritis: 2-year quality-flife results f the randmised, cntrlled, SWEFOT trial. Ann Rheum Dis Dec;72(12):

19 11. Krause ML, Amin A, and Makl A. Use f DMARDs and bilgics during pregnancy and lactatin in rheumatid arthritis: what the rheumatlgist needs t knw. Ther Adv Musculskelet Dis Oct; 6(5): Micrmedex Healthcare Series [Internet Database]. Greenwd Village, Cl: Thmsn Healthcare. Updated peridically. Accessed 8/28/ Menter A, Gttlieb A, Feldman SR, et al. Guidelines f care fr the management f psriasis and psriatic arthritis: Sectin 1. Overview f psriasis and guidelines f care fr the treatment f psriasis with bilgics. J Am Acad Dermatl May;58(5): Menter A, Krman NJ, Elmets CA, et al. Guidelines f care fr the treatment f psriasis and psriatic arthritis: case-based presentatins and evidence-based cnclusins. J Am Acad Dermatl 2011;65: Orencia (abatacept) [package insert]. Bristl-Myers Squibb C. Princetn (NJ): June Peper SM, Lew R, Mikuls T, et al. Rheumatid Arthritis Treatment After Methtrexate: The Durability f Triple Therapy Versus Etanercept. Arthritis Care Res (Hbken) Oct;69(10): Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy utcme in wmen with inflammatry bwel disease fllwing expsure t 5-aminsalicylic acid drugs: a meta-analysis. Reprd. Txicl;2008:25, Ringld S, Weiss PF, Beukelman T Update f the 2011 American Cllege f Rheumatlgy Recmmendatins fr the Treatment f Juvenile Idipathic Arthritis, Recmmendatins fr the Medical Therapy f Children With Systemic Juveline Idipathic Arthritis and Tuberculsis Screening Amng Children Receiving Bilgic Medicatins. Arthritis & Rheumatism. Oct 2013;65(10): Sallit C, Dugads M, Gssec L. Risk f serius infectins during rituximab, abatacept and anakinra therapies fr rheumatid arthritis: meta-analyses f randmized placeb-cntrlled trials. Ann Rheum Dis Jan Sctt DL, Ibrahim F, Farewell V, et al. Tumur necrsis factr inhibitrs versus cmbinatin intensive therapy with cnventinal disease mdifying anti-rheumatic drugs in established rheumatid arthritis: TACIT nn-inferirity randmised cntrlled trial. BMJ Mar 13;350:h Singh JA, Saag KG, Bridges SL Jr, et al American Cllege f Rheumatlgy Guideline fr the Treatment f Rheumatid Arthritis. Arthritis Care Res (Hbken) Jan;68(1): Smlen JS, Landewé R, Bijlsma J, et al. EULAR recmmendatins fr the management f rheumatid arthritis with synthetic and bilgical disease-mdifying antirheumatic drugs: 2016 update. Ann Rheum Dis Jun;76(6): Tynjälä P, Vähäsal P, Tarkiainen M, et al. Aggressive cmbinatin drug therapy in very early plyarticular juvenile idipathic arthritis (ACUTE-JIA): a multicentre randmised pen-label clinical trial. Ann Rheum Dis Sep;70(9): van Vllenhven RF, Gebrek P, Frslind K, et al. Cnventinal cmbinatin treatment versus bilgical treatment in methtrexate-refractry early rheumatid arthritis: 2 year fllw-up f the randmised, nn-blinded, parallel-grup Sweft trial. Lancet May 5;379(9827): Vera-Llnch M, Massartti E, Wlfe F, et al. Cst-effectiveness f abatacept in patients with mderately t severely active rheumatid arthritis and inadequate respnse t methtrexate. Rheumatlgy (Oxfrd) Apr; 47(4): Weinblatt ME, Schiff M, Valente R, et al. Head-t-head cmparisn f subcutaneus abatacept versus adalimumab fr rheumatid arthritis: findings f a phase IIIb, multinatinal, prspective, randmized study. Arthritis Rheum Jan;65(1):28-38.

20 COMMITTEE APPROVAL: This Medical Cverage Guideline (MCG) was apprved by the Flrida Blue Pharmacy Cverage Cmmittee n 09/12/18. GUIDELINE UPDATE INFORMATION: 06/15/07 New Medical Cverage Guideline. 10/15/07 Revisin; cnsisting f updating ICD-9 cding. 05/15/08 Review and revisin; cnsisting f adding new JIA indicatin, updating dsage and administratin sectin, updating references and updating ICD-9 file. 09/15/09 Review and revisin; cnsisting f updating references and updating precautins. 04/15/10 Revisin; cnsisting f adding specific cntinuatin criteria. 08/15/10 Review and revisin; cnsisting f updating references, descriptin and precautins. 02/15/11 Revisin; cnsisting f frmatting changes and ICD-10 cdes. 08/15/11 Review and revisin t guideline; cnsisting f updating cding and references. 11/15/11 Revisin t guideline; cnsisting f adding new dsage frmulatin and maximum dse. 08/15/12 Review and revisin t guideline; cnsisting f updating psitin statement, precautins, exceptins and references. 09/15/12 Revisin t guideline; cnsisting f mdifying cntinuatin criteria. 04/15/13 Revisin t guideline; cnsisting f revising and refrmatting psitin statement; revising and refrmatting descriptin, dsage/administratin, and precautins sectins; updating references and related guidelines. 09/15/13 Review and revisin t guideline; cnsisting f updating quantity limit, adding Orphan drug indicatins, prgram exceptins, and updating references. 01/01/14 Revisin t guideline; cnsisting f updating preferred language.

21 04/15/14 Revisin t guideline; cnsisting f revising psitin statement. 09/15/14 Review and revisin t guideline; cnsisting f updating psitin statement, references, cding, and related guidelines. 09/15/15 Review and revisin t guideline; cnsisting f updating descriptin sectin, psitin statement, billing/cding, and references. 10/01/15 Revisin cnsisting f update t Prgram Exceptins sectin. 12/15/15 Revisin cnsisting f ICD-10 cding updates. 09/15/16 Review and revisin t guideline cnsisting f updating descriptin sectin, psitin statement, billing/cding, and references. 06/15/17 Revisin t guideline cnsisting f updating descriptin sectin, psitin statement, dsage/administratin sectin, and references based n expanded FDA-apprval f JIA indicatin t age 2 years f age and lder and new SQ dsage recmmendatins fr JIA. 10/15/17 Review and revisin t guideline cnsisting f updating descriptin, psitin statement, dsage/administratin, cding/billing, definitins, related guidelines, and references. 01/01/18 Revisin t guideline cnsisting f updating the preferred self-administered bilgic prducts accrding t indicatin fr use. Secukinumab is nw a preferred prduct fr psriatic arthritis, and use f three preferred prducts is required. Tfacitinib (Xeljanz, Xeljanz XR) added as prerequisite therapy fr rheumatid arthritis indicatin. 07/01/18 Revisin t guideline cnsisting f updating the psitin statement. 10/15/18 Review and revisin t guideline cnsisting f updating the psitin statement, billing/cding, related guidelines, and references.