RESPIRATORY INTERLEUKINS (CINQAIR, FASENRA, AND NUCALA )

Transcription

1 RESPIRATORY INTERLEUKINS (CINQAIR, FASENRA, AND NUCALA ) UnitedHealthcare Oxfrd Clinical Plicy Plicy Number: PHARMACY T2 Effective Date: April 1, 2018 Table f Cntents Page INSTRUCTIONS FOR USE... 1 CONDITIONS OF COVERAGE... 1 BENEFIT CONSIDERATIONS... 2 COVERAGE RATIONALE... 2 U.S. FOOD AND DRUG ADMINISTRATION... 6 BACKGROUND... 6 APPLICABLE CODES... 7 CLINICAL EVIDENCE... 7 REFERENCES POLICY HISTORY/REVISION INFORMATION Related Plicy Acquired Rare Disease Drug Therapy Exceptin Prcess INSTRUCTIONS FOR USE This Clinical Plicy prvides assistance in interpreting Oxfrd benefit plans. Unless therwise stated, Oxfrd plicies d nt apply t Medicare Advantage members. Oxfrd reserves the right, in its sle discretin, t mdify its plicies as necessary. This Clinical Plicy is prvided fr infrmatinal purpses. It des nt cnstitute medical advice. The term Oxfrd includes Oxfrd Health Plans, LLC all f its subsidiaries as apprpriate fr these plicies. When deciding cverage, the member specific benefit plan dcument must be referenced. The terms f the member specific benefit plan dcument [e.g., Certificate f Cverage (COC), Schedule f Benefits (SOB), /r Summary Plan Descriptin (SPD)] may differ greatly frm the stard benefit plan upn which this Clinical Plicy is based. In the event f a cnflict, the member specific benefit plan dcument supersedes this Clinical Plicy. All reviewers must first identify member eligibility, any federal r state regulatry requirements, the member specific benefit plan cverage prir t use f this Clinical Plicy. Other Plicies may apply. UnitedHealthcare may als use tls develped by third parties, such as the MCG Care Guidelines, t assist us in administering health benefits. The MCG Care Guidelines are intended t be used in cnnectin with the independent prfessinal medical judgment f a qualified health care prvider d nt cnstitute the practice f medicine r medical advice. CONDITIONS OF COVERAGE Applicable Lines f Business/ Prducts This plicy applies t Oxfrd Cmmercial plan membership. Benefit Type General Benefits Package Referral Required N (Des nt apply t nn-gatekeeper prducts) Authrizatin Required Yes 1,2 (Precertificatin always required fr inpatient admissin) Precertificatin with Medical Directr Review Required Yes 1 Applicable Site(s) f Service (If site f service is nt listed, Medical Directr review is required) Outpatient Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 1 f 12

2 Special Cnsideratins 1 Prviders must call Oxfrd s Medical Management Department t btain precertificatin, with required review by a Medical Directr r their designee. 2 New Jersey Small Members shuld refer t their certificate f cverage fr precertificatin guidelines quantity limit guidelines. BENEFIT CONSIDERATIONS Befre using this plicy, please check the member specific benefit plan dcument any federal r state mates, if applicable. Sme Certificates f Cverage allw fr cverage f experimental/investigatinal/unprven treatments fr lifethreatening illnesses when certain cnditins are met. The member-specific benefit plan dcument must be cnsulted t make cverage decisins fr this service. Sme states mate benefit cverage fr ff-label use f medicatins fr sme diagnses r under sme circumstances when certain cnditins are met. Where such mates apply, they supersede language in the benefit dcument r in the medical r drug plicy. Benefit cverage fr an therwise unprven service fr the treatment f serius rare diseases may ccur when certain cnditins are met. Refer t Oxfrd s Acquired Rare Disease Drug Therapy Exceptin Prcess plicy. Essential Health Benefits fr Individual Small Grup Fr plan years beginning n r after January 1, 2014, the Affrdable Care Act f 2010 (ACA) requires fully insured nn-grfathered individual small grup plans (inside utside f Exchanges) t prvide cverage fr ten categries f Essential Health Benefits ( EHBs ). Large grup plans (bth self-funded fully insured), small grup ASO plans, are nt subject t the requirement t ffer cverage fr EHBs. Hwever, if such plans chse t prvide cverage fr benefits which are deemed EHBs, the ACA requires all dllar limits n thse benefits t be remved n all Grfathered Nn-Grfathered plans. The determinatin f which benefits cnstitute EHBs is made n a state by state basis. As such, when using this plicy, it is imprtant t refer t the member specific benefit plan dcument t determine benefit cverage. COVERAGE RATIONALE This plicy prvides infrmatin abut the use f certain specialty pharmacy medicatins administered by either the subcutaneus (SC) r intravenus (IV) rute. This plicy refers t the fllwing drug prducts, which are interleukin-5 (IL-5) antagnists: Cinqair (reslizumab) Fasenra (benralizumab) Nucala (meplizumab) Prven Esinphilic Granulmatsis with Plyangiitis (EGPA) Nucala Nucala fr subcutaneus use is prven medically necessary fr the treatment f EGPA 1 when all f the fllwing criteria are met: Diagnsis f relapsing r refractry EGPA as defined by all f the fllwing: 13 Diagnsis with EPGA; Past medical histry r presence f asthma; One f the fllwing values at diagnsis: Bld esinphil level f at least 10% f leuccytes Abslute esinphil cunt > 1,000 cells/µl Presence f at least tw f the fllwing characteristics typical f EGPA: Histpathlgical evidence f: - Esinphilic vasculitis - Perivascular esinphilic infiltratin - Esinphil-rich granulmatus inflammatin Neurpathy, mn r ply (mtr deficit r nerve cnductin abnrmality) Pulmnary infiltrates, nn-fixed Sin-nasal abnrmality Cardimypathy (established by echcardigraphy r MRI) Glmerulnephritis (hematuria, red cell casts, prteinuria) Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 2 f 12

3 Alvelar hemrrhage (by brnchalvelar lavage) Palpable purpura Anti-neutrphil cytplasmic antibdy (ANCA) psitive Histry f relapsing r refractry disease defined as ne f the fllwing: Relapsing disease as defined as a past histry (within the past 2 years) f at least ne EGPA relapse (requiring additinal r dse escalatin f crticsterids r immunsuppressant, r hspitalizatin). Refractry disease as defined as failure t attain remissin within the prir 6 mnths fllwing inductin treatment with stard therapy regimens; Patient is currently taking stard therapy (crticsterids with r withut immunsuppressive therapy); Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (benralizumab) Xlair (malizumab) Nucala dsing fr EGPA is in accrdance with the U. S. Fd Drug Administratin apprved labeling: 300mg subcutaneusly nce every 4 weeks; Prescribed by r in cnsultatin with a pulmnlgist, rheumatlgist, r allergist/immunlgist; Initial authrizatin will be fr n mre than 6 mnths Reauthrizatin/Cntinuatin f Care Criteria: Nucala, fr the treatment f EGPA, authrizatin fr cntinued use will be apprved based n all f the fllwing criteria: Dcumentatin f psitive clinical respnse as demnstrated by at least ne f the fllwing: Reductin in the frequency /r severity f relapses. Reductin r discntinuatin f dses f crticsterids /r immunsuppressant. Disease remissin Reductin in severity r frequency f EGPA-related symptms Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (benralizumab) Xlair (malizumab) Nucala dsing fr EGPA is in accrdance with the U. S. Fd Drug Administratin apprved labeling: 300mg subcutaneusly nce every 4 weeks; Prescribed by r in cnsultatin with a pulmnlgist, rheumatlgist, r allergist/immunlgist; Reauthrizatin will be fr n mre than 12 mnths Severe Asthma Cinqair Cinqair fr intravenus use is prven medically necessary fr add-n therapy fr patients wh meet BOTH f the fllwing criteria: 2 Have an esinphilic phentype Will be used as add-n maintenance therapy in the treatment f severe asthma Cinqair is medically necessary when ALL f the fllwing criteria are met: 2-6 Diagnsis f severe asthma; Classificatin f asthma as uncntrlled r inadequately cntrlled as defined by at least ne f the fllwing: Pr symptm cntrl (e.g., ACQ scre cnsistently greater than 1.5 r ACT scre cnsistently less than 20); r Tw r mre bursts f systemic crticsterids fr at least 3 days each in the previus 12 mnths; r Asthma-related emergency treatment (e.g., emergency rm visit, hspital admissin, r unscheduled physician s ffice visit fr nebulizer r ther urgent treatment); r Airflw limitatin (e.g., after apprpriate brnchdilatr withhld FEV1 less than 80% predicted [in the face f reduced FEV1/FVC defined as less than the lwer limit f nrmal]); Asthma is an esinphilic phentype as defined by a baseline (pre-reslizumab) peripheral bld esinphil level f 400 cells/μl within the past 4 weeks; Used in cmbinatin with ne f the fllwing: One maximally-dsed (apprpriately adjusted fr age) cmbinatin ICS/LABA prduct [e.g., fluticasne prpinate/salmeterl (Advair ), budesnide/frmterl (Symbicrt )]; r Cmbinatin therapy including bth f the fllwing: Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 3 f 12

4 One high-dse (apprpriately adjusted fr age) ICS prduct [e.g., ciclesnide (Alvesc ), mmetasne furate (Asmanex ), beclmethasne diprpinate (QVAR )]; One additinal asthma cntrller medicatin [e.g., LABA - ldaterl (Striverdi ) r indacaterl (Arcapta ), leuktriene receptr antagnist mntelukast (Singulair ), thephylline] Patient is nt receiving Cinqair in cmbinatin with either f the fllwing: Fasenra (benralizumab) Nucala (meplizumab) Xlair (malizumab) Cinqair dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 3 mg/kg intravenusly nce every 4 weeks; Prescribed by r in cnsultatin with a pulmnlgist r allergist/immunlgist; Initial authrizatin will be fr n mre than 6 mnths Fasenra Fasenra fr subcutaneus use is prven medically necessary fr add-n therapy fr patients wh meet BOTH f the fllwing criteria: Has an esinphilic phentype Will be used as add-n maintenance therapy in the treatment f severe asthma 3, 5, 6, Fasenra is medically necessary when ALL f the fllwing criteria are met: Diagnsis f severe asthma; Classificatin f asthma as uncntrlled r inadequately cntrlled as defined by at least ne f the fllwing: Pr symptm cntrl (e.g., Asthma Cntrl Questinnaire [ACQ] scre cnsistently greater than 1.5 r Asthma Cntrl Test [ACT] scre cnsistently less than 20); r Tw r mre bursts f systemic crticsterids fr at least 3 days each in the previus 12 mnths; r Asthma-related emergency treatment (e.g., emergency rm visit, hspital admissin, r unscheduled physician s ffice visit fr nebulizer r ther urgent treatment); r Airflw limitatin (e.g., after apprpriate brnchdilatr withhld frced expiratry vlume in 1 secnd [FEV1] less than 80% predicted [in the face f reduced FEV1/frced vital capacity [FVC] defined as less than the lwer limit f nrmal]); Asthma is an esinphilic phentype as defined by a baseline (pre- benralizumab treatment) peripheral bld esinphil level 150 cells/μl within the past 6 weeks 12 ; Used in cmbinatin with ne f the fllwing: One maximally-dsed (apprpriately adjusted fr age) cmbinatin inhaled crticsterid (ICS)/lng-acting beta 2 -agnist (LABA) prduct [e.g., fluticasne prpinate/salmeterl (Advair ), budesnide/frmterl (Symbicrt )]; r Cmbinatin therapy including bth f the fllwing: One high-dse (apprpriately adjusted fr age) ICS prduct [e.g., ciclesnide (Alvesc ), mmetasne furate (Asmanex ), beclmethasne diprpinate (QVAR )]; One additinal asthma cntrller medicatin [e.g., LABA - ldaterl (Striverdi ) r indacaterl (Arcapta ); leuktriene receptr antagnist mntelukast (Singulair ); thephylline] Patient is nt receiving Fasenra in cmbinatin with either f the fllwing: Cinqair (reslizumab) Nucala (meplizumab) Xlair (malizumab) Fasenra dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 30mg subcutaneusly nce every 4 weeks fr 3 dses, then nce every 8 weeks thereafter; Prescribed by r in cnsultatin with a pulmnlgist r allergist/immunlgist; Initial authrizatin will be fr n mre than 6 mnths Nucala Nucala fr subcutaneus use is prven medically necessary fr add-n therapy fr patients wh meet BOTH f the fllwing criteria: 1 Has an esinphilic phentype Will be used as add-n maintenance therapy in the treatment f severe asthma Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 4 f 12

5 Nucala is medically necessary when ALL f the fllwing criteria are met: 1,3-6 Diagnsis f severe asthma; Classificatin f asthma as uncntrlled r inadequately cntrlled as defined by at least ne f the fllwing: Pr symptm cntrl (e.g., Asthma Cntrl Questinnaire [ACQ] scre cnsistently greater than 1.5 r Asthma Cntrl Test [ACT] scre cnsistently less than 20); r Tw r mre bursts f systemic crticsterids fr at least 3 days each in the previus 12 mnths; r Asthma-related emergency treatment (e.g., emergency rm visit, hspital admissin, r unscheduled physician s ffice visit fr nebulizer r ther urgent treatment); r Airflw limitatin (e.g., after apprpriate brnchdilatr withhld frced expiratry vlume in 1 secnd [FEV1] less than 80% predicted [in the face f reduced FEV1/frced vital capacity [FVC] defined as less than the lwer limit f nrmal]); Asthma is an esinphilic phentype as defined by a baseline (pre-meplizumab treatment) peripheral bld esinphil level 150 cells/μl within the past 6 weeks; Used in cmbinatin with ne f the fllwing: One maximally-dsed (apprpriately adjusted fr age) cmbinatin inhaled crticsterid (ICS)/lng-acting beta 2 -agnist (LABA) prduct [e.g., fluticasne prpinate/salmeterl (Advair ), budesnide/frmterl (Symbicrt )]; r Cmbinatin therapy including bth f the fllwing: One high-dse (apprpriately adjusted fr age) ICS prduct [e.g., ciclesnide (Alvesc ), mmetasne furate (Asmanex ), beclmethasne diprpinate (QVAR )]; One additinal asthma cntrller medicatin [e.g., LABA - ldaterl (Striverdi ) r indacaterl (Arcapta ); leuktriene receptr antagnist mntelukast (Singulair ); thephylline] Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (beralizumab) Xlair (malizumab) Nucala dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 100mg subcutaneusly nce every 4 weeks; Prescribed by r in cnsultatin with a pulmnlgist r allergist/immunlgist; Initial authrizatin will be fr n mre than 6 mnths Reauthrizatin/Cntinuatin f Care Criteria Fr patients currently n Cinqair, Fasenra, r Nucala fr the treatment f severe esinphilic asthma, authrizatin fr cntinued use will be apprved based n all f the fllwing criteria: Dcumentatin f psitive clinical respnse as demnstrated by at least ne f the fllwing: Reductin in the frequency f exacerbatins Decreased utilizatin f rescue medicatins Increase in percent predicted FEV1 frm pretreatment baseline Reductin in severity r frequency f asthma-related symptms (e.g., wheezing, shrtness f breath, cughing, etc.) Used in cmbinatin with an ICS-cntaining cntrller medicatin; One f the fllwing: Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (benralizumab) Xlair (malizumab) r Patient is nt receiving Cinqair in cmbinatin with either f the fllwing: Fasenra (benralizumab) Nucala (meplizumab) Xlair (malizumab) Patient is nt receiving Fasenra in cmbinatin with either f the fllwing: Cinqair (reslizumab) Nucala (meplizumab) Xlair (malizumab) Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 5 f 12

6 One f the fllwing: Nucala dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 100mg subcutaneusly nce every 4 weeks; r Cinqair dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 3 mg/kg intravenusly nce every 4 weeks; r Fasenra dsing fr severe esinphilic asthma is in accrdance with the United States Fd Drug Administratin apprved labeling: 30 mg subcutaneusly nce every 8 weeks; Prescribed by r in cnsultatin with a pulmnlgist r allergist/immunlgist; Reauthrizatin will be fr n mre than 12 mnths Unprven/Nt Medically Necessary Cinqair, Fasenra, Nucala are unprven nt medically necessary in the fllwing: 1-2,8 Other esinphilic cnditins Acute brnchspasm Status asthmaticus Chrnic bstructive pulmnary disease (COPD) Granulmatsis with plyangiitis (Wegener s) Micrscpic plyangiitis Organ r Life-threatening EGPA U.S. FOOD AND DRUG ADMINISTRATION (FDA) Cinqair (reslizumab) Cinqair is apprved by the U.S. Fd Drug Administratin (FDA) fr the add-n maintenance treatment f patients with severe asthma aged 18 years lder, wh have an esinphilic phentype. Cinqair is nt indicated fr the treatment f ther esinphilic cnditins r fr acute brnchspasm r status asthmaticus. Because f the risk f anaphylaxis, healthcare prviders administering Cinqair shuld bserve patients clsely fr an apprpriate perid f time be prepared t manage anaphylaxis that can be life-threatening. 2 Fasenra (benralizumab) Fasenra is apprved by the U.S. Fd Drug Administratin (FDA) fr the add-n maintenance treatment f patients with severe asthma aged 12 years lder, wh have an esinphilic phentype. Fasenra is nt indicated fr the treatment f ther esinphilic cnditins r fr acute brnchspasm r status asthmaticus. 10 Nucala (meplizumab) Nucala is apprved by the U.S. Fd Drug Administratin (FDA) fr the add-n maintenance treatment f patients with severe asthma aged 12 years lder, wh have an esinphilic phentype. Nucala is nt indicated fr the treatment f ther esinphilic cnditins r fr acute brnchspasm r status asthmaticus. Nucala is als indicated fr the treatment f adult patient with esinphilic granulmatsis with plyangitis (EGPA). 1 BACKGROUND Asthma is a cmmn chrnic inflammatry disease f the airways that affects an estimated 24 millin adults children. Althugh the disease is well cntrlled with inhaled therapy in mst patients, apprximately millin peple have severe asthma (i.e., 5-10% f the asthma ppulatin) that is assciated with substantial mrbidity, mrtality, ecnmic effects. Asthma has been divided int subtypes, sme f which are assciated with airway inflammatin with esinphils. It is estimated that abut half f individuals with severe asthma exhibit the esinphilic phentype with elevated esinphil levels (a marker f inflammatin) in bth the bld airways. Activated esinphils can increase airway smth muscle cntractin mucus secretin, which are hallmarks f asthma. Interleukin-5 (IL-5) is an imprtant cellular signal in esinphilic inflammatin. Therapies that decrease IL-5 levels, such as Nucala (meplizumab) Cinqair (reslizumab), may decrease esinphils in lung tissue. Fasenra (benralizumab) directly binds t the human IL-5 receptr n the surface f esinphils basphils, leading t the apptsis f these cells thrugh antibdy-dependent cell mediated cyttxicity. 4,7,9,10 Esinphilic granulmatsis with plyangiitis (EGPA, Churg-Strauss syndrme) is characterized by asthma, sinusitis, pulmnary infiltrates, neurpathy, esinphilic vasculitis f ne r mre end rgans. It is thught that esinphils mediate the effects in patients with EGPA by infiltrating tissue vasculature, causing inflammatin. Systemic gluccrticids are currently the stard f treatment fr EGPA, hwever, sme patients t nt have sufficient respnse t therapy. Meplizumab, by inhibiting IL-5 signaling, reduces the prductin survival f esinphils; hwever, the mechanism f meplizumab actin in asthma EGPA has nt been definitively established. 1,13 Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 6 f 12

7 APPLICABLE CODES The fllwing list(s) f prcedure /r diagnsis cdes is prvided fr reference purpses nly may nt be all inclusive. Listing f a cde in this plicy des nt imply that the service described by the cde is a cvered r nncvered health service. Benefit cverage fr health services is determined by the member specific benefit plan dcument applicable laws that may require cverage fr a specific service. The inclusin f a cde des nt imply any right t reimbursement r guarantee claim payment. Other Plicies may apply. HCPCS Cde J2182 J2786 Injectin, meplizumab, 1 mg Injectin, reslizumab, 1 mg Descriptin ICD-10 Diagnsis Cde Descriptin J45.50 Severe persistent asthma, uncmplicated J45.51 Severe persistent asthma with (acute) exacerbatin J45.52 Severe persistent asthma with status asthmaticus J82 Pulmnary esinphilia, nt elsewhere classified M30.1 Plyarteritis with lung invlvement [Churg-Strauss] CLINICAL EVIDENCE Prven/Medically Necessary Esinphilic Granulmatsis with Plyangiitis (EGPA) Meplizumab is indicated fr the treatment f adult patients with esinphilic granulmatsis with plyangiitis (EGPA). 1 In a multicenter, duble-blind, parallel-grup, phase 3 trial, Wechsler et al, evaluated the efficacy safety meplizumab versus placeb fr esinphilic granulmatsis with plyangiitis (EGPA). 13 Patients with relapsing r refractry EGPA were rmly assigned t receive 300 mg f meplizumab (n=68) r placeb (n=68) subcutaneusly every 4 weeks, plus stard care, fr 52 weeks. Patients had t have received treatment fr at least 4 weeks were taking stable crticsterid dsing fr at least 4 weeks. The tw primary end pints were the accrued weeks f remissin ver the 52 week perid, the prprtin f participants in remissin at bth week 36 week 48. Secndary endpints included: time t first relapse average daily gluccrticid use at weeks 48 thrugh 52). Patients receiving meplizumab had significantly mre accrued weeks f remissin than placeb (28% vs. 3% had 24 weeks f accrued remissin; dds rati, 5.91; 95% cnfidence interval [CI], 2.68 t 13.03; P<0.001) a higher percentage f patients were in remissin at bth week 36 week 48 (32% vs. 3%; dds rati, 16.74; 95% CI, 3.61 t 77.56; P<0.001). Remissin did nt ccur in 47% f the patients in the meplizumab grup versus 81% f thse in the placeb grup. The annualized relapse rate was 1.14 in the meplizumab grup, as cmpared with 2.27 in the placeb grup (rate rati, 0.50; 95% CI, 0.36 t 0.70; P<0.001). A ttal f 44% f the patients in the meplizumab grup, as cmpared with 7% f thse in the placeb grup, had an average daily dse f prednislne r prednisne f 4.0 mg r less per day during weeks 48 thrugh 52 (dds rati, 0.20; 95% CI, 0.09 t 0.41; P<0.001). The authrs cncluded that in patients with EGPA, meplizumab resulted in significantly mre weeks in remissin a higher prprtin f patients in remissin than placeb, althugh nly half f the patients treated with meplizumab had prtcl-defined remissin. Severe Esinphilic Asthma Benralizumab is indicated fr the add-n maintenance treatment f patients with severe asthma aged 12 years lder, with an esinphilic phentype. 10 Meplizumab is indicated fr the add-n maintenance treatment f patients with severe asthma aged 12 years lder, with an esinphilic phentype. 1 Reslizumab is indicated fr the add-n maintenance treatment f patients with severe asthma aged 18 years lder, with an esinphilic phentype. 2 Prfessinal Scieties Severe Esinphilic Asthma The Glbal Initiative fr Asthma (GINA, 2017) recmmends that fr Step 5 treatment, adults adlescents, aged 12 years ld may be treated with meplizumab r reslizumab) as fllws (Evidence B: Rmized cntrlled trials meta-analyses. Limited bdy f evidence): 6 Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 7 f 12

8 Step 5: Higher level care /r add-n treatment. Patients with persistent symptms r exacerbatins despite crrect inhaler technique gd adherence with Step 4 treatment in whm ther cntrller ptins have been cnsidered, shuld be referred t a specialist with expertise in management f severe asthma (Evidence D: Panel cnsensus judgment). Treatment ptins that may be cnsidered at Step 5 (in nt already tried) include: add-n anti-interleukin-5 treatment (subcutaneus meplizumab, intravenus reslizumab): (anti-interleukin-5 treatment) fr patients aged 12 years ld with severe esinphilic asthma that is uncntrlled n Step 4 treatment (Evidence B). On March 14, 2016, the Institute fr Clinical Ecnmic Review (ICER) released a clinical reprt entitled, Meplizumab (Nucala, GlaxSmithKline plc.) fr the Treatment f Severe Asthma with Esinphilia: Effectiveness, Value, Value-Based Price Benchmarks. ICER recmmendatins are as fllws: 4 ICER judges the current bdy f evidence n meplizumab t be cmparable r better. Fr adult patients with severe esinphilic asthma, ICER judges there t be mderate certainty f a cmparable r better net benefit fr meplizumab 100mg SC every fur weeks as add-n maintenance treatment cmpared with stard f care including high dse ICS, LABA, additinal cntrller medicatins. There is mderate certainty because bth the MENSA trial, which demnstrated a significant reductin in asthma exacerbatins, the SIRIUS trial, which demnstrated a significant reductin in ral crticsterids dsage, were relatively small studies f shrt duratin. There remains uncertainty abut the lng-term durability f the benefits f the therapy abut the ptential harms frm mdulatin f the immune system. Onging pst-marketing trials extensin studies evaluating meplizumab may demnstrate a wide variety f utcmes, frm substantial net health benefit t a cmparable net benefit given the ptential harms assciated with the mnclnal antibdy (pprtunist infectin, anaphylaxis). The Eurpean Respiratry Sciety (ERS)/American Thracic Sciety (ATS) guidelines define severe asthma as that which requires treatment with high-dse ICSs plus a secnd cntrller (r systemic crticsterids) t prevent prgressin t uncntrlled disease status r cntinuing uncntrlled disease status despite this therapy. 3 The guidelines recmmend that, While the anti-il5 antibdy, meplizumab, was nt beneficial in unselected adult patients with mderate asthma, when studied in severe asthma patients with persistent sputum esinphilia, tw anti- IL-5 antibdies, meplizumab reslizumab, have been shwn t decrease exacerbatins ral crticsterid use, as well as imprve symptms lung functin t varying degrees. Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 8 f 12

9 Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 9 f 12

10 Unprven/Nt Medically Necessary Nucala Cinqair have additinal uses listed in the FDA-label: 1-2 Acute brnchspasm Chrnic bstructive pulmnary disease (COPD) Other esinphilic cnditins Status asthmaticus Statistically rbust rmized cntrlled trials are necessary t establish the safety efficacy f Fasenra, Nucala Cinqair t treat these cnditins. 1-2,8,10 REFERENCES The freging Oxfrd plicy has been adapted frm an existing UnitedHealthcare Pharmacy Clinical Pharmacy Prgram that was researched, develped apprved by the UnitedHealth Grup Natinal Pharmacy & Therapeutics Cmmittee. [2018D0055C] 1. Nucala [prescribing infrmatin]. Research Triangle Park, NC; GlaxSmithKline, LLC; December Cinqair [prescribing infrmatin]. Frazer, PA; Teva Respiratry, LLC; May Chung KF, Wenzel SE, Brzek JL, et al. Internatinal ERS/ATS guidelines n definitin, evaluatin treatment f severe asthma. Eur Respir J Feb:43(2): Institute fr Clinical Ecnmic Review (ICER). Meplizumab (Nucala, GlaxSmithKline plc.) fr the Treatment f Severe Asthma with Esinphilia: Effectiveness, Value, Value-Based Price Benchmarks. March 14, Available at Accessed April 25, Glbal Initiative fr Asthma. Glbal Strategy fr Asthma Management Preventin, Available at Accessed June 19, Bel EH, Wenzel SE, Thmpsn PJ, Prazma CM, et al. Oral Gluccrticid-Sparing Effect f Meplizumab in Esinphilic Asthma. New Eng J Med Sept:371(13): Parameswaran KN, Dasgupta A, et al. Meplizumab in COPD with Esinphilic Brnchitis: A Rmized Clinical Trial. Pster sessin presented at the Annual Meeting f the American Academy f Allergy, Asthma Immunlgy, Ls Angeles, CA. March 6, Centers fr Disease Cntrl Preventin. Asthma. Available at Accessed May 16, Natinal Heart, Lung Bld Institute. Explre Asthma. Available at Accessed May 16, Fasenra [prescribing infrmatin]. Wilmingtn, DE; AstraZeneca Pharmaceuticals LP; Nvember FitzGerald JM, Bleecker ER, Menzies-Gw A, et al. Predictrs f enhanced respnse with benralizumab fr patients with severe asthma: pled analysis f the SIROCCO CALIMA studies. Lancet Respir Med Sep Gldman M, Hirsch I, Zangrilli JG, et al. The assciatin between bld esinphil cunt benralizumab efficacy fr patients with severe, uncntrlled asthma: subanalyses f the Phase III SIROCCO CALIMA studies. Curr Med Res Opin Sep;33(9): Wechsler ME, Akuthta P, Jayne D, et al. Meplizumab r placeb fr esinphilic granulmatsis with plyangiitis. N Engl J Med 2017; 376: POLICY HISTORY/REVISION INFORMATION Date 04/01/2018 Actin/Descriptin Revised cverage ratinale: Replaced language indicating this plicy prvides infrmatin abut the use f certain specialty pharmacy medicatins administered by either the subcutaneus (SC) r intravenus (IV) rute fr severe asthmatic cnditins with this plicy prvides infrmatin abut the use f certain specialty pharmacy medicatins administered by either the subcutaneus (SC) r intravenus (IV) rute Added cverage guidelines fr esinphilic granulmatsis with plyangiitis (EGPA) t indicate: Initial Therapy Nucala fr subcutaneus use is prven fr the treatment f EGPA Nucala is medically necessary fr the treatment f EGPA when all f the fllwing criteria are met: Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 10 f 12

11 Date Actin/Descriptin - Diagnsis f relapsing r refractry EGPA as defined by all f the fllwing: Diagnsis with EPGA, Past medical histry r presence f asthma, One f the fllwing values at diagnsis: Bld esinphil level f at least 10% f leuccytes Abslute esinphil cunt > 1,000 cells/µl Presence f at least tw f the fllwing characteristics typical f EGPA: Histpathlgical evidence f: Esinphilic vasculitis Perivascular esinphilic infiltratin Esinphil-rich granulmatus inflammatin Neurpathy, mn r ply (mtr deficit r nerve cnductin abnrmality) Pulmnary infiltrates, nn-fixed Sin-nasal abnrmality Cardimypathy (established by echcardigraphy r MRI) Glmerulnephritis (hematuria, red cell casts, prteinuria) Alvelar hemrrhage (by brnchalvelar lavage) Palpable purpura Anti-neutrphil cytplasmic antibdy (ANCA) psitive Histry f relapsing r refractry disease defined as ne f the fllwing: Relapsing disease as defined as a past histry (within the past 2 years) f at least ne EGPA relapse (requiring additinal r dse escalatin f crticsterids r immunsuppressant, r hspitalizatin) Refractry disease as defined as failure t attain remissin within the prir 6 mnths fllwing inductin treatment with stard therapy regimens - Patient is currently taking stard therapy (crticsterids with r withut immunsuppressive therapy); - Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (benralizumab) Xlair (malizumab) - Nucala dsing fr EGPA is in accrdance with the U. S. Fd Drug Administratin apprved labeling: 300mg subcutaneusly nce every 4 weeks; - Prescribed by r in cnsultatin with a pulmnlgist, rheumatlgist, r allergist/immunlgist; - Initial authrizatin will be fr n mre than 6 mnths Reauthrizatin/Cntinuatin f Care Criteria Authrizatin fr cntinued use f Nucala fr the treatment f EGPA will be apprved based n all f the fllwing criteria: - Dcumentatin f psitive clinical respnse as demnstrated by at least ne f the fllwing: Reductin in the frequency /r severity f relapses Reductin r discntinuatin f dses f crticsterids /r immunsuppressant Disease remissin Reductin in severity r frequency f EGPA-related symptms - Patient is nt receiving Nucala in cmbinatin with either f the fllwing: Cinqair (reslizumab) Fasenra (benralizumab) Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 11 f 12

12 Date Actin/Descriptin Xlair (malizumab) - Nucala dsing fr EGPA is in accrdance with the U. S. Fd Drug Administratin apprved labeling: 300mg subcutaneusly nce every 4 weeks; - Prescribed by r in cnsultatin with a pulmnlgist, rheumatlgist, r allergist/immunlgist; - Reauthrizatin will be fr n mre than 12 mnths Updated list f unprven nt medically necessary indicatins; added: Granulmatsis with plyangiitis (Wegener s) Micrscpic plyangiitis Organ r life-threatening EGPA Updated list f applicable ICD-10 diagnsis cdes; added M30.1 Updated supprting infrmatin t reflect the mst current backgrund infrmatin, clinical evidence, FDA infrmatin, references Archived previus plicy versin PHARMACY T2 Respiratry Interleukins (Cinqair, Fasenra, Nucala ) Page 12 f 12