Subject: Baricitinib (Olumiant ) Tablet

Transcription

1 09-J Original Effective Date: 09/15/18 Reviewed: 08/08/18 Revised: 00/00/00 Subject: Baricitinib (Olumiant ) Tablet 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: Baricitinib (Olumiant) is an ral Janus kinase (JAK) inhibitr initially apprved by the US Fd and Drug Administratin (FDA) in May 2018 fr treatment f adult patients with mderately t severely active rheumatid arthritis wh have had an inadequate respnse t ne r mre tumr necrsis factr (TNF) antagnist therapies. Many mediatrs in autimmune inflammatin (e.g., interleukins 2, 6, 12, 15, and 23; interferns; and granulcyte macrphage clny-stimulating factr [GM-CSF]) signal thrugh the JAK family (JAK1, JAK2, JAK3, and tyrsine kinase 2 [Tyk2]). Baricitinib is the secnd JAK inhibitr t be apprved by the FDA fr the treatment f RA; the first being tfacitinib (Xeljanz) in Nvember Tfacitinib has the greatest affinity fr JAK3, but it is cnsidered a pan-jak inhibitr (inhibitry activity at all but JAK3>JAK1>JAK2). Baricitinib is a ptent JAK1 and JAK2 inhibitr with minimal activity n JAK3. Other JAK inhibitrs are develpment, and each has a unique inhibitry prfile amng the varius JAK prteins. The clinical significance f the different JAK affinity prfiles amng the varius JAK inhibitrs has yet t be determined. Prir t FDA-apprval, baricitinib had been previusly granted rphan drug designatin fr the treatment f pediatric systemic lupus erythematsus in Nvember The safety and efficacy f baricitinib leading t FDA-apprval was assessed in a clinical develpment prgram that included tw dse-ranging trials and fur cnfirmatry phase 3 trials. Althugh ther dses have been studied, the FDA-recmmended dse f baricitinib is 2 mg nce daily. The dse-ranging studies included a 12-week randmized cmparisn f baricitinib 1, 2, 4, and 8 mg daily vs. placeb. In dse-ranging Study 1, the bserved ACR20 respnse rate was similar fr baricitinib 1 and 2 mg daily and fr baricitinib 4 and 8 mg daily, with the highest respnse fr baricitinib 8 mg daily. Hwever, in dseranging Study 2, there was nt a clear trend f dse respnse, with similar respnse rates fr 1 mg and 4 mg, and 2 mg and 8 mg. The efficacy and safety f the FDA-apprved 2 mg daily dsage was assessed in tw 24-week, randmized, duble-blind, multicenter studies in patients with active rheumatid arthritis. In Study III (NCT ) patients with mderately t severely active RA wh had an inadequate

2 respnse r intlerance t cnventinal DMARDs (cdmards) received baricitinib 2 mg r 4 mg nce daily r placeb added t existing backgrund cdmard treatment. In Study 4 (NCT ) patients with mderately t severely active RA wh had an inadequate respnse r intlerance t ne r mre TNF inhibitr therapies with r withut ther bilgic DMARDs received baricitinib 2 mg r baricitinib 4 mg nce daily r placeb added t backgrund cdmard treatment. In bth studies frm Week 16, nnrespnding patients culd be rescued t receive baricitinib 4 mg nce daily. The primary endpint in bth trials was the prprtin f patients wh achieved an ACR20 respnse at Week 12. Other key endpints included ACR20, ACR50, and ACR70 respnses and Disease Activity Scre (DAS28-CRP) <2.6 at Week 12 and Week 24. A summary f the treatment respnses fr the 2 mg daily dsage are prvided in Table 1 belw. TABLE 1 Study 3 Study 4 Placeb + cdmards (n=228) Baricitinib 2 mg/day + cdmards (n=229) Placeb + cdmards (n=228) Baricitinib 2 mg/day + cdmards (n=229) ACR 20 Week 12 39% 66% 27% 49% Week 24 42% 61% 27% 45% ACR 50 Week 12 13% 34% 8% 20% Week 24 21% 41% 13% 23% ACR 70 Week 12 3% 18% 2% 13% Week 24 8% 25% 3% 13% DAS28-CRP<2.6 Week 12 9% 26% 4% 11% Week 24 11% 31% 6% 11%

3 In 2015, the American Cllege f Rheumatlgy (ACR) published an updated guideline fr the treatment f rheumatid arthritis. The guidelines d nt address the use f baricitinib as it was apprved well after the cmpletin f the guidelines. The next guideline update is expected in late 2019 r early The guidelines d supprt the use f anther JAK inhibitr tfacitinib. The guidelines supprt the use f tfacitinib in the fllwing scenaris: (1) 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); (2) patients with established RA if disease activity remains mderate r high despite use f multiple TNFi therapies, use tfacitinib, with r withut MTX, ver anther TNFI, with r withut MTX, if use f a nn- TNF bilgic is nt an ptin; and (3) 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, then use tfacitinib, with r withut MTX, ver anther TNFI. Tfacitinib is als recmmended as an ptin when patients must avid a TNFi due t cngestive heart failure. 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 if given with flic acid when 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 FDA 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) in a prvider-administered setting such as an utpatient hspital, ambulatry surgical suite, physician ffice, r emergency facility is nt cnsidered medically necessary. 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)

4 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 baricitinib (Olumiant) meets the definitin f medical necessity when BOTH f the fllwing criteria are met ( 1 and 2 ): 1. Baricitinib will be used fr the treatment f an indicatin listed in Table 2, and ALL indicatinspecific and maximum-allwable dsage criteria are met 2. Baricitinib will NOT be administered in cmbinatin with ANY f the fllwing: a. abatacept (Orencia) b. adalimumab (Humira) c. anakinra (Kineret) d. apremilast (Otezla) 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)

5 Table 2: Indicatins and Specific Criteria Indicatin Criteria Maximum Allwable Dsage Rheumatid arthritis (RA) When ALL f the fllwing are met ( 1 t 6 ): 1. Member s disease is mderately t severely active 2. Member is 18 years f age r lder 3. Member des nt have ANY f the fllwing baseline lab abnrmalities ( a, b, c, r d ): a. ALC less than 500 cells/mm 3 b. ANC less than 1,000 cell/mm 3 c. egfr f less than 60 ml/min/1.73 m 2 d. Hgb less than 8 g/dl 4. Member has had an inadequate respnse (i.e., unable t achieve remissin r lw disease activity) t at least three cntinuus mnths f therapy with TWO r mre 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 the 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) 5. EITHER f the fllwing ( a r b ): a. Member has had an inadequate respnse, persistent and intlerable adverse effects, r a cntraindicatin t TWO r mre f the fllwing self-administered bilgics (the specific adverse effects and/r cntraindicatins must be prvided): i. adalimumab (Humira) ii. iii. etanercept (Enbrel) glimumab (Simpni) 2 mg PO nce daily

6 b. Alternatives t the use f an anti-tnf bilgic shuld be cnsidered due t a prduct warning and/r precautin fr EITHER f the fllwing (the specific cnditin must be prvided): i. Current r wrsening cngestive heart failure ii. Demyelinating disease (e.g., multiple sclersis) 6. 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) Orphan Indicatins Pediatric systemic lupus erythematsus (SLE) When ALL f the fllwing are met ( 1, 2, 3, and 4 ): 1. Member s diagnsis has been cnfirmed by a psitive test fr antinuclear antibdies (ANA) dcumentatin f the labratry must be submitted 2. Member is less than 18 years f age 3. Member has had an inadequate respnse, intlerable adverse effects, r cntraindicatins t ALL f the fllwing treatments ( a, b, and c ): a. Crticsterid (e.g., prednisne) b. Hydrxychlrquine c. At least ne nn-bilgic immunsuppressant (e.g., azathiprine, cyclphsphamide, methtrexate, mycphenlate mfetil) 2 mg PO nce daily Apprval duratin: 6 mnths ALC: abslute lymphcyte cunt, ANC: abslute neutrphil cunt, csdmard: cnventinal synthetic disease mdifying anti-rheumatic drug, egfr: estimated glmerular filtratin rate, Hgb: hemglbin *NOTE: if the member has had an inadequate respnse t previus bilgic therapy that is FDAapprved fr RA, the member is NOT required t have had an inadequate therapeutic respnse t nnbilgic prerequisite therapy (e.g., fr rheumatid arthritis, if member has previusly had an inadequate respnse t adalimumab, but des nt have a histry f inadequate respnse t methtrexate, they d nt have t try methtrexate t meet medical necessity criteria). Hwever, the preferred self-administered (i.e., subcutaneus) bilgic prduct requirement must still be met.

7 Cntinuatin f baricitinib (Olumiant) meets the definitin f medical necessity when ALL f the fllwing criteria are met ( 1 t 4 ): 1. An authrizatin r reauthrizatin fr baricitinib has been previusly apprved by Flrida Blue r anther health plan in the past 2 years fr the treatment f a cnditin listed in Table 2, OR the member has previusly met ALL indicatin-specific initiatin criteria 2. Member has demnstrated a beneficial respnse t therapy with baricitinib 3. Baricitinib will NOT be administered in cmbinatin with ANY f the fllwing: a. abatacept (Orencia) b. adalimumab (Humira) c. anakinra (Kineret) d. apremilast (Otezla) 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) s. sarilumab (Kevzara) l. secukinumab (Csentyx) m. tildrakizumab-asmn (Ilumya) n. tcilizumab (Actemra). tfacitinib (Xeljanz, Xeljanz XR) p. ustekinumab (Stelara) q. vedlizumab (Entyvi) 4. The dsage f baricitinib des nt exceed 2 mg nce daily Apprval duratin: 1 year 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

8 Treatment f adult patients with mderately t severely active rheumatid arthritis wh have had an inadequate respnse t ne r mre tumr necrsis factr (TNF) antagnist therapies Limitatin f Use (per prduct labeling): Use f baricitinib in cmbinatin with ther JAK inhibitrs, bilgic disease-mdifying antirheumatic drugs (DMARDs), r with ptent immunsuppressants such as azathiprine and cyclsprine is nt recmmended. The recmmended dsage is 2 mg nce daily. Baricitinib may be used as mntherapy r in cmbinatin with methtrexate r ther DMARDs. Baricitinib is given rally with r withut fd. Initiatin is nt recmmended in patients with an abslute lymphcyte cunt (ALC) less than 500 cells/mm 3, abslute neutrphil cunt (ANC) less than 1,000 cells/mm 3, r hemglbin (Hg) level less than 8 g/dl. Als, prir t initiating baricitinib, test patients fr latent tuberculsis (TB). If psitive, cnsider treating fr TB prir t baricitinib use. Dse Adjustments Adverse effects: Serius infectin - hld treatment until the infectin is cntrlled ALC less than interrupt therapy until ALC 500 ANC less than 1,000 - interrupt therapy until ALC 1,000 Hg <8 - interrupt therapy until Hg 8 Hepatic impairment: n dsage adjustment is recmmended fr mild r mderate hepatic impairment. Baricitinib is nt recmmended in patients with severe hepatic impairment due t a lack f data. Renal impairment: baricitinib is nt recmmended in patients with an estimated glmerular filtratin rate (egfr) f less than 60 ml/minute/1.73m 2 Drug Interactins: baricitinib is nt recmmended fr use in patients taking strng Organic Anin Transprter 3 (OAT3) inhibitrs, such as prbenecid Drug Availability 2 mg film-cated, immediate-release tablet PRECAUTIONS: Bxed Warning WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS SERIOUS INFECTIONS Patients treated with Olumiant are at risk fr develping serius infectins that may lead t hspitalizatin r death. Mst patients wh develped these infectins were taking cncmitant immunsuppressants such as methtrexate r crticsterids. If a serius infectin develps, interrupt Olumiant until the infectin is cntrlled. Reprted infectins include: Active tuberculsis, which may present with pulmnary r extrapulmnary disease. Patients shuld be tested fr latent tuberculsis befre initiating Olumiant and during therapy. Treatment fr latent infectin shuld be cnsidered prir t Olumiant use.

9 Invasive fungal infectins, including candidiasis and pneumcystsis. Patients with invasive fungal infectins may present with disseminated, rather than lcalized, disease. Bacterial, viral, and ther infectins due t pprtunistic pathgens. The risks and benefits f treatment with Olumiant shuld be carefully cnsidered prir t initiating therapy in patients with chrnic r recurrent infectin. Patients shuld be clsely mnitred fr the develpment f signs and symptms f infectin during and after treatment with Olumiant including the pssible develpment f tuberculsis in patients wh tested negative fr latent tuberculsis infectin prir t initiating therapy. MALIGNANCIES Lymphma and ther malignancies have been bserved in patients treated with Olumiant. THROMBOSIS Thrmbsis, including deep venus thrmbsis and pulmnary emblism, has been bserved at an increased incidence in patients treated with Olumiant cmpared t placeb. In additin, there were cases f arterial thrmbsis. Many f these adverse events were serius and sme resulted in death. Patients with symptms f thrmbsis shuld be prmptly evaluated. Cntraindicatins Nne Precautins/Warnings Serius Infectins, Malignances, and Thrmbsis see Bxed Warning Gastrintestinal Perfratins - Events f gastrintestinal perfratin have been reprted in clinical studies with baricitinib, althugh the rle f JAK inhibitin in these events is nt knwn. Baricitinib shuld be used with cautin in patients wh may be at increased risk fr gastrintestinal perfratin (e.g., patients with a histry f diverticulitis). Patients presenting with new nset abdminal symptms shuld be evaluated prmptly fr early identificatin f gastrintestinal perfratin. Labratry Abnrmalities Neutrpenia - Treatment with baricitinib was assciated with an increased incidence f neutrpenia cmpared t placeb. Avid initiatin r interrupt treatment in patients with an ANC less than 1,000 cells/mm 3. Evaluate at baseline and thereafter accrding t rutine patient management. Lymphpenia - ALC less than 500 cells/mm 3 were reprted in clinical trials. Lymphcyte cunts less than the lwer limit f nrmal were assciated with infectin in patients treated with baricitinib, but nt placeb. Avid initiatin r interrupt treatment in patients with an ALC less than 500 cells/mm 3. Evaluate at baseline and thereafter accrding t rutine patient management. Anemia - Decreases in hemglbin levels t less than 8 g/dl were reprted in clinical trials. Avid initiatin r interrupt treatment in patients with hemglbin less than 8 g/dl. Evaluate at baseline and thereafter accrding t rutine patient management. Liver Enzyme Elevatins - Treatment was assciated with increased incidence f liver enzyme elevatin cmpared t placeb. Increases t greater than r equal t 5x and greater than r equal t 10x ULN were bserved fr bth ALT and AST in patients in clinical trials. Evaluate at baseline and thereafter accrding t rutine patient management. Prmpt investigatin f the cause f liver enzyme elevatin is recmmended t identify ptential cases f drug-induced liver

10 injury. If increases in ALT r AST are bserved and drug-induced liver injury is suspected, interrupt baricitinib until this diagnsis is excluded. Lipid Elevatins - Treatment with baricitinib was assciated with increases in lipid parameters, including ttal chlesterl, lw-density lipprtein (LDL) chlesterl, and high-density lipprtein (HDL) chlesterl. Assessment f lipid parameters shuld be perfrmed apprximately 12 weeks fllwing initiatin. Manage patients accrding t clinical guidelines fr the management f hyperlipidemia. Vaccinatins - Avid use f live vaccines with baricitinib. Update immunizatins in agreement with current immunizatin guidelines prir t initiating baricitinib therapy. BILLING/CODING INFORMATION: The fllwing cdes may be used t describe: HCPCS Cding C9399 J8499 Unclassified drugs r bilgicals (Hspital Outpatient Use ONLY) Prescriptin drug, ral, nn-chemtherapeutic, Nt Otherwise Specified ICD-10 Diagnses Cdes That Supprt Medical Necessity 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

11 M06.30 M06.39 Rheumatid ndule M06.80 M06.89 Other specified rheumatid arthritis M06.9 Rheumatid arthritis, 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 Part D: BCBSF has delegated t Prime Therapeutics authrity t make cverage determinatins fr the Medicare Part D services referenced in this guideline. Medicare Advantage: N Natinal Cverage Determinatin (NCD) and/r Lcal Cverage Determinatin (LCD) were fund at the time f guideline creatin. DEFINITIONS: DMARDs: An acrnym fr disease-mdifying antirheumatic drugs. 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., tfacitinib, apremilast), and (3) bilgical DMARDs (bdmard), which can be either a bisimilar DMARD (bsdmard) r bilgical riginatr DMARD Rheumatid arthritis: usually strikes between ages 20 and 50. Inflammatin begins in a jint, usually thse f the fingers and hands, resulting in pain, swelling, redness, and eventually jint defrmity. It is cnsidered an autimmune disease, which can affect the entire bdy, causing fatigue, weight lss, weakness, fever, and lss f appetite. It affects each persn differently, with symptms ranging frm mild t debilitating. In many cases, it is difficult t cntrl. In abut ne in six cases, rheumatid arthritis becmes severely debilitating and can shrten the life f the persn affected. RELATED GUIDELINES: Abatacept (Orencia), 09-J

12 Adalimumab (Humira), 09-J Anakinra (Kineret), 09-J Certlizumab Pegl (Cimzia), 09-J Etanercept (Enbrel), 09-J Glimumab (Simpni, Simpni Aria), 09-J Infliximab Prducts [infliximab (Remicade), infliximab-dyyb (Inflectra), and infliximab-abda (Renflexis)], 09-J Rituximab (Rituxan), 09-J Sarilumab (Kevzara), 09-J Tcilizumab (Actemra), 09-J Tfacitinib (Xeljanz, Xeljanz XR) Tablets, 09-J OTHER: Table 2: DMARD Generic Name Auranfin (ral gld) Azathiprine Chlrambucil Cyclphsphamide Cyclsprine Gld sdium thimalate (injectable gld) Hydrxychlrquine sulfate Leflunmide Methtrexate Mincycline Penicillamine Sulfasalazine DMARD Brand Name Ridaura Imuran Leukeran Cytxan Neral, Sandimmune Mychrysine Plaquenil Arava Rheumatrex, Trexall Mincin Cuprimine, Depen Azulfidine, Azulfidine EN-Tabs Grading f Severity f Rheumatid Arthritis Severity Criteria Mild Jint pain

13 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 Mderate Severe Between 6 and 20 inflamed jints 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 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. Clinical Pharmaclgy [database nline]. Tampa, FL: Gld Standard, Inc.; Available at: Accessed 7/11/ Dugads M, van der Heijde D, Chen YC, et al: Baricitinib in patients with inadequate respnse r intlerance t cnventinal synthetic DMARDs: results frm the RA-BUILD study. Ann Rheum Dis 2017; 76(1): Genvese MC, Kremer J, Zamani O, et al: Baricitinib in patients with refractry rheumatid arthritis. N Engl J Med 2016; 374(13): 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 qualityf-life results f the randmised, cntrlled, SWEFOT trial. Ann Rheum Dis Dec;72(12): Kunwar S, Cllins CE, and Cnstantinescu F. Baricitinib, a Janus kinase inhibitr, in the treatment f rheumatid arthritis: a systematic literature review and meta-analysis f randmized cntrlled trials. Clin Rheumatl Jul 13. [Epub ahead f print]. 7. 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 7/11/18.

14 9. Olumiant (baricitinib) package insert. Indianaplis, IN: Eli Lilly and Cmpany; May 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, 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): Taylr PC, Keystne EC, van der Heijde D, et al. Baricitinib versus Placeb r Adalimumab in Rheumatid Arthritis. N Engl J Med Feb 16;376(7): van der Heijde D, Dugads M, Chen YC, et al. Effects f baricitinib n radigraphic prgressin f structural jint damage at 1 year in patients with rheumatid arthritis and an inadequate respnse t cnventinal synthetic disease-mdifying antirheumatic drugs. RMD Open May 8;4(1):e 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): Wright TB and Punar M. Paediatric systemic lupus erythematsus: insights frm translatinal research. Rheumatlgy (Oxfrd) Apr 1;56(suppl_1):i24-i31. COMMITTEE APPROVAL: This Medical Cverage Guideline (MCG) was apprved by the BCBSF Pharmacy Plicy Cmmittee n 08/08/18. GUIDELINE UPDATE INFORMATION: 09/15/18 New Medical Cverage Guideline.