Guideline for the Prescribing of Biologic Therapy in adult patients ( 16 years) with active and progressive Psoriatic Arthritis (PsA) within NHS Fife

Transcription

1 Guideline fr the Prescribing f Bilgic Therapy in adult patients ( 16 years) with active and prgressive Psriatic Arthritis (PsA) within NHS Fife Dcument Number & Versin Versin 1.0 Date Ratified: 20/12/16 Ratified by: Managed Service Drug & Therapeutics Cmmittee Next Review Date: 20/12/18 Dcument Authr(s): Stephanie Hart, Rheumatlgy Pharmacist Reviewed by: Dr Helen Harris, Cnsultant Rheumatlgist, FRDU. Dr Jane Gibsn, Cnsultant Rheumatlgist, FRDU. Dr Steven Byle, Cnsultant Rheumatlgist, FRDU.

2 1. Intrductin The management f psriatic arthritis (PsA) is aimed at suppressing inflammatin in all dmains f the disease, including peripheral arthritis, axial disease, enthesitis, dactylitis, psriasis and nail disease invlvement. Current practice is aimed at early diagnsis and interventin with disease mdifying anti-inflammatry medicines (DMARDs) then, if necessary, prgressin t bilgical therapy t suppress persistent inflammatin and imprve utcmes. 2. Principles The prtcl utilises current available natinal guidance t ptimise treatment in terms f clinical utcmes and cst-effectiveness. Optimal management f all the dmains f psriatic disease is a challenge and will require cllabratin between rheumatlgy and dermatlgy departments in many cases. 3. Eligibility fr treatment with bilgic therapy Peripheral arthritis (plyarticular disease) 1 Patients must: Have active arthritis defined as at least three tender and three swllen jints. Have failed treatment with at least tw cnventinal DMARDs, administered either individually r in cmbinatin. An adequate therapeutic trial is defined as either failure t tlerate a DMARD r active disease despite treatment f at least 12 weeks at the target therapeutic dse f cnventinal DMARDs (e.g. leflunmide, methtrexate, sulfasalazine r ciclsprin) 2 Oligarthritis Bilgic therapy shuld be cnsidered in patients with severe persistent ligarthritis (fewer than three tender / swllen jints), which has a majr demnstrable influence n well-being and wh have failed treatment with at least tw cnventinal DMARDs and apprpriate intra-articular sterids Exclusin criteria 3 Reference shuld be made t the individual summary f prduct characteristics fr each medicine but imprtant exclusins include: Active serius infectin Septic arthritis f a native jint within the last 12 mnths r sepsis f a prsthetic jint within the last 12 mnths, r indefinitely if the jint remains in situ New Yrk Heart Assciatin (NYHA) grade 3 r 4 cngestive cardiac failure (CCF) Clear histry f demyelinating disease Malignancy TNF inhibitrs are cntraindicated in interstitial lung disease 2

3 Extreme cautin needs t be taken in the fllwing circumstances 3 : Patients prne t infectin fr example: Chrnic leg ulcers Persistent r recurrent chest infectins Indwelling urinary catheter Patients with hepatitis B infectin (treat with anti-viral if indicated, mnitr serum amintransminases and HBV DNA lad during therapy) Patients with hepatitis C infectin (mnitr serum amintransminases and HCV RNA lad during therapy) Patients wh are HIV psitive Previus TB (cnsider prphylactic anti-mycbacterial therapy in latent TB) Prir histry f malignancy unless the malignancy was diagnsed and treated > 10 years ag Pre-malignant cnditins such as Barrett s esphagus, cervical dysplasia and large bwel plyps New Yrk Heart Assciatin (NYHA) grade 1 r 2 5. Pre-bilgic Screening The fllwing tests must be cmpleted and reprted as nrmal prir t treatment with bilgic therapy: Exclude TB: Chest x-ray (within past 6 mnths) IGRA if any f the fllwing risk factrs: Persnal/ family histry f TB N evidence f BCG Asian/ Eastern Eurpean in rigin Recent travel t cuntry f high incidence f TB Hep B surface antigen Hep B cre antibdy Hep C cre antigen HIV FBC, U&Es, LFTs 6. Bld Mnitring during bilgic therapy Anti-TNF, Ustekinumab, Secukinumab Bilgic mntherapy: FBC/CRP, U&Es and LFTs ne week prir t attending utpatient rheumatlgy clinic appintments fr disease mnitring Bilgic plus cncmitant cdmard FBC/CRP, LFTs and U&Es - Refer t the bld mnitring requirements in the Shared Care Agreement fr the particular ral DMARD 3

4 7. Alternative t bilgic therapy in PsA 4 Apremilast (Otezla ) is an ral phphdiesterase-4 inhibitr accepted fr restricted use within NHS Sctland either alne r in cmbinatin with disease mdifying anti-rheumatic drugs (DMARDs), fr the treatment f active PsA in adult patients wh have had an inadequate respnse with at least tw prir DMARD therapies r wh are intlerant f such therapies. Apremilast may be cnsidered as a suitable treatment ptin prir t bilgic therapy in thse patients whm adherence t bld mnitring is cnsidered t be a cncern, thse patients wh wuld prefer a tablet ver injectin and as a treatment when ther drugs are cntraindicated. NB with the emergence f bisimilars, apremilast is nw mre expensive than sme bilgic therapy. 4

5 8. Bilgic Treatment pathway When a patient is eligible fr bilgic treatment, a bilgics referral frm is cmpleted and the chice f bilgic will be agreed at the Virtual Bilgics Clinic (VBC), taking int cnsideratin previus treatment and c-mrbidities. The VBC is held n a weekly basis and cnsists f at least 2 cnsultant rheumatlgists, the rheumatlgy pharmacist and a rheumatlgy nurse specialist. The time frame frm the decisin t start bilgic treatment t administratin f first injectin is 6 weeks. If psriasis is severe, treatment needs t be agreed with dermatlgy and share the cst f the bilgic. 1 st line bilgic therapy: Secukinumab 150mg dse - nt t be used in patients with inflammatry bwel disease (IBD). mab anti-tnf with lwest acquisitin cst in patient with IBD t be discussed with GI. Patients with uveitis t be agreed with Ophthalmlgy. 2 nd line bilgic therapy: In the case f bilgic failure, in patients nt previusly treated with Etanercept (Enbrel r Benepali), Benepali will be cnsidered as the next treatment ptin unless cntraindicated/ nt apprpriate. mab anti-tnf with lwest acquisitin cst in patients already treated with Etanercept (Enbrel r Benepali)/ patients with IBD. Secukinumab 300mg (if agreed t share csts with Dermatlgy in severe psriasis) nt t be used in patients with IBD. 3 rd line bilgic therapy: Ustekinumab 4 th line bilgic therapy: Abatacept (ff-label, blanket ULM frm apprved) 5

6 9. Pregnancy, breast feeding and paternal expsure Patients wh are (r planning t becme) pregnant and/r breastfeeding, men planning t cnceive and patients wh have accidentally cnceived shuld discuss treatment ptins with their rheumatlgist 5. Infliximab may be cntinued until 16 weeks. Etanercept and adalimumab may be cntinued until the end f the secnd trimester. T ensure lw/n levels f drug in crd bld at delivery, etanercept and adalimumab shuld be avided in the third trimester and infliximab stpped at 16 weeks. If these drugs are cntinued later in pregnancy t treat active disease, then live vaccines shuld be avided in the infant until 7 mnths f age. Certlizumab pegl is cmpatible with all three tri- mesters f pregnancy and has reduced placental transfer cmpared with ther TNF inhibitrs (TNFis). Glimumab is unlikely t be harmful in the first trimester Wmen shuld nt be discuraged frm breast- feeding n TNFis, but cautin is recmmended until further infrmatin is available. Based n limited evidence infliximab, etanercept and adalimumab are cmpatible with paternal expsure Fllwing 4 nenatal deaths frm disseminated BCG r tuberculsis infectins after expsure t a TNF-inhibitr in uter, the MHRA have prduced advice stating that live attenuated vaccines are cntraindicated in infancy up until 6 mnths fllwing in uter expsure t TNF-inhibitrs and ther bilgics, after which time vaccinatin shuld be cnsidered 6. Any infant wh has been expsed t immunsuppressive treatment frm the mther via breastfeeding shuld have any live attenuated vaccinatin deferred fr as lng as a pstnatal influence n the immune status f the infant remains pssible. At the pint f writing, the nly live vaccine, which frms part f immunisatin prgramme, is the rtavirus, and selected infants may als receive the live BCG vaccine if deemed t be at risk f TB. The rheumatlgist shuld include in their crrespndence with primary care a statement f their pinin n the patient s suitability fr the vaccine. Ustekinumab 7 Wmen f childbearing ptential Wmen f childbearing ptential shuld use effective methds f cntraceptin during treatment and fr at least 15 weeks after treatment. Pregnancy There are n adequate data frm the use f ustekinumab in pregnant wmen. Animal studies d nt indicate direct r indirect harmful effects with respect t pregnancy, embrynic/fetal develpment, parturitin r pstnatal develpment. As a precautinary measure, it is preferable t avid use in pregnancy. Breast-feeding It is unknwn whether ustekinumab is excreted in human breast milk. Animal studies have shwn excretin f ustekinumab at lw levels in breast milk. It is 6

7 nt knwn if ustekinumab is absrbed systemically after ingestin. Because f the ptential fr adverse reactins in nursing infants frm ustekinumab, a decisin n whether t discntinue breast-feeding during treatment and up t 15 weeks after treatment r t discntinue therapy with STELARA must be made taking int accunt the benefit f breast-feeding t the child and the benefit f STELARA therapy t the wman. Fertility The effect f ustekinumab n human fertility has nt been evaluated. In animal studies neither adverse effects n male fertility indices nr birth defects r develpmental txicity were bserved. Secukinumab 8 Wmen f childbearing ptential Wmen f childbearing ptential shuld use an effective methd f cntraceptin during treatment and fr at least 20 weeks after treatment. Pregnancy There are n adequate data frm the use f secukinumab in pregnant wmen. Animal studies d nt indicate direct r indirect harmful effects with respect t pregnancy, embrynic/fetal develpment, parturitin r pstnatal develpment (see sectin 5.3). As a precautinary measure, it is preferable t avid the use f Csentyx in pregnancy. Breast-feeding It is nt knwn whether secukinumab is excreted in human milk. Immunglbulins are excreted in human milk and it is nt knwn if secukinumab is absrbed systemically after ingestin. Because f the ptential fr adverse reactins in nursing infants frm secukinumab, a decisin n whether t discntinue breast-feeding during treatment and up t 20 weeks after treatment r t discntinue therapy with Csentyx must be made taking int accunt the benefit f breast-feeding t the child and the benefit f Csentyx therapy t the wman. Fertility The effect f secukinumab n human fertility has nt been evaluated. Animal studies d nt indicate direct r indirect harmful effects with respect t fertility. Apremilast 9 Wmen f childbearing ptential Pregnancy shuld be excluded befre treatment can be initiated. Wmen f childbearing ptential shuld use an effective methd f cntraceptin t prevent pregnancy during treatment. Pregnancy There are limited data abut the use f apremilast in pregnant wmen. Apremilast is cntraindicated during pregnancy. Breast-feeding Apremilast was detected in milk f lactating mice. It is nt knwn whether apremilast, r its metablites, are excreted in human milk. A risk t the breastfed infant cannt be excluded; therefre apremilast shuld nt be used 7

8 during breast-feeding. Fertility N fertility data is available in humans. In animal studies in mice, n adverse effects n fertility were bserved in males at expsure levels 3-fld clinical expsure and in females at expsure levels 1-fld clinical expsure. 10. Peri-perative infectin risk 3 The ptential benefit f preventing pst-perative infectins by stpping bilgic treatment prir t surgery shuld be balanced against the risk f peri-perative flare in PsA disease activity. Shuld treatment be stpped prir t surgery, this shuld be stpped at 3 5 times the drugs half-life Bilgic Half life (days) * Time (weeks) ## Etanercept 3 (apprx. 70hurs) 2 weeks Adalimumab 14 Certlizumab 14 Glimumab 12 +/- 3 days 6 weeks Infliximab 9 Secukinumab 27 (ranging 18 46) 11 weeks Ustekinumab 21 (ranging 15 32) 9 weeks * Frm current Summary f Prduct Characteristics (available nline at httl:// ## Time frame agreed within rheumatlgy department Bilgic therapy can be recmmenced 2 weeks after surgery prvided there is n evidence f infectin and the wund is healing well. 11. Vaccinatin advice Patients with PsA n immunsuppressive therapy, e.g. DMARD r bilgic shuld be ffered pneumcccal vaccine and influenza vaccinatin. Ideally, these shuld be administered at least 2 weeks prir t starting methtrexate r a bilgic agent 10. Hwever, treatment shuld nt be delayed as a result f timing f immunisatins. In these circumstances, the respnse rate t a nn-live vaccine may be reduced. FRDU advcates patients being treated with immunsuppressant s shuld be revaccinated against pneumcccus every five years 11, 12. The administratin f live attenuated vaccines is cntraindicated when administering bilgic agents. There is n cntraindicatin fr the administratin f live vaccines t relatives f patients n immunsuppressant drugs; clse cntacts shuld be fully immunised. Public Health England advise that t minimise the risk f infectin in immunsuppressed individuals fr whm live vaccines are cntraindicated, their clse cntacts shuld be fully immunised accrding t the UK schedule, as a matter f pririty. Clse cntacts f severely immunsuppressed individuals shuld als be ffered vaccinatin against varicella and influenza. This will reduce the risk f expsure f vulnerable individuals t the serius cnsequences f vaccine-preventable infectins 6. 8

9 On ceasing treatment with a TNF-inhibitr, live vaccinatin is permitted after a perid f 3 mnths (1-2 mnths in the case f Etanercept) 13,14. Bilgic therapy must nt be restarted fr at least 2 weeks, preferably 4 weeks fllwing administratin f a live attenuated vaccine 13, Herpes zster (shingles) vaccinatin 15 The herpes zster vaccinatin (shingles) is a live vaccine and is recmmended t thse aged 70 years (a catch-up prgramme is als being rlled ut in thse aged 70_79). The Green bk has updated and it has defined when herpes zster vaccinatin is cntraindicated in certain immunsuppressed patients, dependent upn the degree f immunsuppressin (see belw). This means that sme PsA patients may be eligible fr the vaccine prir t cmmencing bilgic therapy. In these patients, a perid f 2 4 weeks shuld be delayed prir t starting bilgic therapy. The herpes zster vaccine shuld nt be given t 15 : thse wh are receiving r have received in the past 12 mnths bilgical therapy (e.g. anti-tnf therapy such as alemtuzumab, fatumumab and rituximab) unless therwise directed by a specialist - NB see statement abve regarding live vaccines. thse wh are receiving r have received in the past 3 mnths immunsuppressive therapy including shrt term high-dse crticsterids (>40mg prednislne per day fr mre than 1 week); lng term lwer dse crticsterids (>20mg prednislne per day fr mre than 14 days) nn-bilgical ral immune mdulating drugs e.g. methtrexate >25mg per week, azathiprine >3.0mg/kg/day r 6-mercaptpurine >1.5mg/kg/day FRDU have agreed that patients n the fllwing DMARD s are nt cnsidered sufficiently immunsuppressed and eligible patients may receive the herpes zster vaccinatin. Herpes zster vaccinatin is allwed in eligible patients treated with the fllwing: Azathiprine ( 3mg/kg/day) Leflunmide Ciclsprin Methtrexate ( 25mg per week) Hydrxychlrquine Mycrisin (IM gld) Prednislne ( 20mg per day) Patients n cmbinatin therapy with 2, 3 r all f the fllwing hydrxychlrquine, sulphasalazine, methtrexate ( 25mg per week) and Prednislne ( 20mg per day) Patients in cmbinatin therapy with Azathiprine ( 3mg/kg/day) and prednislne ( 20mg per day) Herpes zster vaccinatin is cntraindicated in patients treated with the fllwing: Any bilgic therapy Cmbinatin therapy nt mentined abve e.g. methtrexate and leflunmide Cyclphsamide Mycphenlate Mfetil (MMF) Tacrlimus 9

10 12. Outcme measure The Psriatic Arthritis Respnse Criteria (PsARC) with a jint cunt is recmmended as the clinical respnse criteria fr peripheral PsA. A PsARC respnse is defined as imprvement in tw factrs (with at least ne being a jint scre) with wrsening f nne f the fllwing fur factrs 1 : Patient glbal assessment (n a 0-5 Likert Scale) Physician glbal assessment (imprvement is defined as decrease by 1 unit; wrsening defined as increase by 1 unit.) Tender jint scre Swllen jint scre (imprvement defined as decrease by 30%, wrsening defined as increase 30%) Althugh the PsARC will be the primary jint respnse. An ESR r CRP, a patient pain assessment (visual analgue scre 0-10cm), will als be dne and this will enable a Disease Activity Scre (DAS) 28 t be calculated. Lw r minimal disease activity (MDA) is the ultimate gal f therapy. A patient with PsA is in MDA when they meet 5/7 f the fllwing criteria: Tender jint cunt ( 1) Swllen jint cunt ( 1) PASI ( 1) HAQ ( 0.5) Tender entheseal pints ( 1) Patient pain VAS ( 15) Patient glbal activity VAS ( 20) 13. Respnse criteria Patients treated with anti-tnf therapy r ustekinumab will be assessed initially after 3 mnths f treatment. Treatment shuld be cntinued in patients wh have respnded 1. In the case f nn-respnders t anti-tnf, cnsideratin will be given t a further 3 mnths f treatment if there has been a partial respnse and then cntinuing therapy if there has been a full respnse cmpared t baseline 2. Patients n apremilast r secukinumab will be assessed initially after 4 mnths f treatment. If patient shws n evidence f therapeutic benefit after 16 weeks, therapy shuld be recnsidered. Treatment shuld be cntinued in patients wh have respnded. In the case f secukinumab, cnsideratin will be given t a further 3 mnths f treatment if there has been a partial respnse and then cntinuing therapy if there has been a full respnse cmpared t baseline 8. The Rheumatlgy nurse specialist r Rheumatlgy pharmacist will assess patients at 3 (r 4) mnths, and then again at 6 mnths. Their cnsultant will then review patients at 9 mnths fllwing initiatin f bilgic therapy. Thereafter, patients will be reviewed regularly, at minimum frequency f annual review fr stable patients. 10

11 If lw r MDA is achieved and maintained, discussin can ccur between clinician and patient t cnsider reducing the frequency f administratin f bilgic therapy. Failure t maintain respnse will result in increase in frequency f injectins, t the previus dse. 11

12 References 1. NICE Technlgy Appraisal Guidance 199. Etanercept, Infliximab & Adalimumab fr the treatment f adults with Psriatic Arthritis. Available frm (accessed 1 st September 2016) 2. British Sciety fr Rheumatlgy. Guideline fr Anti-TNF Therapy in Psriatic Arthritis. Octber Available frm: Full_Guidelines.pdf (accessed 1 st September 2016). 3. Ding T, Ledingham J, Luqmani R et al. BSR and BHPR rheumatid arthritis guidelines n safety f anti-tnf therapies. Rheumatlgy 2010:49: Scttish Medicines Cnsrtium. Summary f Recmmendatins fr Apremilast (Otezla) (N. 1053/15) Available frm: (accessed 1 st September 2016). 5. British Sciety f Rheumatlgy. Prescribing fr rheumatlgical cnditins in pregnancy and breastfeeding. Part 1: standard and bilgic disease mdifying anti-rheumatic drugs and crticsterids. January Available frm (accessed 6th September 2016). 6. Medicines and Healthcare prducts Regulatry Agency. Live attenuated vaccines: avid use in thse wh are clinically immunsuppressed. April Accessed frm (accessed 6th September 2016). 7. Summary f Prduct Characteristics. Ustekinumab. (Stelera ). Electrnic Medicines Cmpendium. Updated June Available frm (accessed 6th September 2016). 8. Summary f Prduct Characteristics. Secukinumab. (Csentyx ). Electrnic Medicines Cmpendium. Updated May Available frm (accessed 6th September 2016). 9. Summary f Prduct Characteristics. Apremilast. (Otezla ). Electrnic Medicines Cmpendium. Updated May Available frm (accessed 6th September 2016). 10. The British Sciety fr Rheumatlgy (BSR) (2011) BSR Statement n Vaccinatin in Adult Patients with Rheumatic Diseases [nline]. Available at ment_nv_2011.pdf (accessed 1 st September 2016). 11. Gyal A, Gyal K, Merla JF. Screening and vaccinatins in patients requiring systemic immunsuppressin: an update fr dermatlgists. American Jurnal f Clinical Dermatlgy. 16:3:

13 12. Centers fr Disease Cntrl and Preventin. Use f PCV13 and PPSV-23 Vaccine fr Adults with Immuncmprmising Cnditins. MMWR. Octber 2012, Vl 61; 40. Available frm (accessed 6th September 2016). 13. Expert pinin frm Dr Derek Slan, Infectius Disease Cnsultant, NHS Fife. 14. Centers fr Disease Cntrl and Preventin. General Recmmendatins n Immunizatin. US advice. January 2011 / 60(RR02);1-60, page Available frm (accessed 18 th Octber 2016). 15. Public Health England. Shingles: the green bk chapter 28a. Updated February Available frm 09_Green_Bk_Chapter_28a_v3_0W.PDF (accessed 6th September 2016). 13