Xeljanz (Tofacitinib)

Transkript

1 Xeljanz (Tofacitinib) Randeep Mandla, Medical Advisor Pfizer Norge AS

2 Xeljanz (Tofacitinib) i behandling av RA Xeljanz (Tofacitinib) Effekt Sikkerhet

3 Xeljanz (Tofacitinib) Tofacitinib - Små-molekylær forbindelse, ikke-biologisk - Virker intracellulært i immunceller - Hemmer Janus Kinase enzym (JAK1/3)

4 Xeljanz (Tofacitinib) Foreslått indikasjon XELJANZ i kombinasjon med metotreksat (MTX) er indisert til behandling av moderat til alvorlig, aktiv revmatoid artritt (RA) hos voksne pasienter som har hatt en utilstrekkelig respons på MTX. XELJANZ kan gis som monoterapi ved intoleranse overfor MTX eller når fortsatt behandling med MTX er uhensiktsmessig. Foreslått dosering Den anbefalte dosen er 5 mg administrert to ganger daglig Xeljanz SPC in approval

5 2016 EULAR Recommendations: Phase II Updated EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease modifying antirheumatic drugs. Convenor: Josef Smolen (tsdmard = target synthetic DMARDs= includes JAK inhibitor)

6 Xeljanz studieprogram Phase 3/4 Clinical Trials Study Patient population # Study Duration ORAL Start MTX naïve #958 Radiographic data Monotherapy Treatment 24 months Tofacitinib 5 or 10 mg BID Primary Endpoints mtss (6 months) ACR70 (6 months) Publication Lee EB et al. N Engl J Med ORAL Scan ORAL Standard ORAL Sync ORAL Solo ORAL Step ORAL Strategy RA LTE Study 1024 MTX-IR #797 MTX-IR #717 DMARD-IR (nonbiologic or biologic) #795 DMARD-IR (nonbiologic or biologic) #611 TNF inhibitor IR #399 MTX-IR #1080 Radiographic data Active control (Adalimumab) Background DMARDs 24 months Tofacitinib 5 or 10 mg BID + MTX 12 months Tofacitinib 5 or 10 mg BID + MTX 12 months Tofacitinib 5 or 10 mg BID +nonbiologic DMARD(s) Monotherapy 6 months Tofacitinib 5 or 10 mg BID TNF-I IR 6 months Tofacitinib 5 or 10 mg BID + MTX vs Adalimumab + MTX 12 months Ongoing Tofacitinib 5 mg BID Mono/ +MTX Estimate # 4500 Long-term safety Ongoing Tofacitinib 5 or 10 mg BID ACR20 (6 months) mtss (6 months) HAQ-DI (3 months) DAS28-4(ESR) <2.6 (6 months) ACR20 (6 months) HAQ-DI (3 months) DAS28-4(ESR) <2.6 (6months) ACR20 (6 months) HAQ-DI (3 months) DAS28-4(ESR) <2.6 (6 months) ACR20 (3 months) HAQ-DI (3 months) DAS28-4(ESR) <2.6 (3 months) ACR20 (3 months) HAQ-DI (3 months) DAS28-4(ESR) <2.6 (3 months) ACR 50 (6 months) AE reports Lab safety van der Heijde D et al. Arthritis Rheum van Vollenhoven RF et al. N Engl J Med Kremer J et al. Ann Intern Med Fleischmann R et al. N Engl J Med Burmester GR et al. Lancet ClinicalTrials.gov Identifier: NCT ClinicalTrials.gov Identifier: NCT ACR=American College of Rheumatology; DAS=disease activity score; DMARD=disease-modifying antirheumatic drug; ESR=erythrocyte sedimentation rate; HAQ-DI=Health Assessment Questionnaire Disability Index; IR=inadequate responder; MTX=methotrexate; mtss= van der Heijde modified total Sharp score; TNF=tumor necrosis factor, BID=twice daily, LTE=LongTerm Extension 6

7 Andel som oppnår ACR20 (FAS, NRI) MTX ACR20 was a co-primary endpoint for all studies except ORAL Start ** * N= ORAL Start MTX-naïve ORAL Scan MTX-IR ORAL Standard ORAL Sync DMARD-IR ORAL Solo (3 mos) ORAL Step (3 mos) TNFi-IR *P 0.05; **P<0.001; P< vs. placebo/mtx. ACR=American College of Rheumatology; BID=twice daily; DMARD=disease-modifying antirheumatic drug; FAS=full analysis set; IR=inadequate response; MTX=methotrexate; NRI=non-responder imputation; SE=standard error; TNFi=tumor necrosis factor inhibitor. 1. Burmester G et al. Lancet. 2013;381: Fleischmann R et al. N Engl J Med. 2012;367: Kremer J et al. Ann Intern Med. 2013;159(4): Van der Heijde D et al. Arthritis Rheum. 2013;65(3): Van Vollenhoven RF et al. N Engl J Med. 2012;367: Lee EB et al. Arthritis Rheum. 2012;64(suppl10):S1049, Abst

8 Andel som oppnår ACR50 (FAS, NRI) MTX ** N= ORAL Start MTX-naïve ORAL Scan MTX-IR ORAL Standard ORAL Sync DMARD-IR ORAL Solo (3 mos) ORAL Step (3 mos) TNFi-IR *P 0.05; **P<0.001; P< vs. placebo/mtx. ACR=American College of Rheumatology; BID=twice daily; DMARD=disease-modifying antirheumatic drug; FAS=full analysis set; IR=inadequate response; MTX=methotrexate; NRI=non-responder imputation; SE=standard error; TNFi=tumor necrosis factor inhibitor. 1. Burmester G et al. Lancet. 2013;381: Fleischmann R et al. N Engl J Med. 2012;367: Kremer J et al. Ann Intern Med. 2013;159(4): Van der Heijde D et al. Arthritis Rheum. 2013;65(3): Van Vollenhoven RF et al. N Engl J Med. 2012;367: Lee EB et al. Arthritis Rheum. 2012;64(suppl10):S1049, Abst

9 Andel som oppnår ACR70 (FAS, NRI) MTX ACR70 was a co-primary endpoint for ORAL Start * * ** * N= ORAL Start MTX-naïve ORAL Scan MTX-IR ORAL Standard ORAL Sync DMARD-IR ORAL Solo (3 mos) ORAL Step (3 mos) TNFi-IR *P 0.05; **P<0.001 ; P< vs. placebo/mtx. ACR 70 was co-primary endpoint for ORAL Start. ACR=American College of Rheumatology; BID=twice daily; DMARD=disease-modifying antirheumatic drug; FAS=full analysis set; IR=inadequate response; MTX=methotrexate; NRI=non-responder imputation; SE=standard error; TNFi=tumor necrosis factor inhibitor. 1. Burmester G et al. Lancet. 2013;381: Fleischmann R et al. N Engl J Med. 2012;367: Kremer J et al. Ann Intern Med. 2013;159(4): Van der Heijde D et al. Arthritis Rheum. 2013;65(3): Van Vollenhoven RF et al. N Engl J Med. 2012;367: Lee EB et al. Arthritis Rheum. 2012;64(suppl10):S1049, Abst

10 Sikkerhet De vanligste alvorlige infeksjonene som er rapportert med XELJANZ er pneumoni, cellulitt, herpes zoster (HZ), urinveisinfeksjon, divertikulitt og appendisitt. Reaktivering av herpes zoster Risiko forhøyet hos japanske og koreanske pasienter samt hos pasienter som har hatt RA lenge og som tidligere har brukt to eller flere biologiske DMARD-er Vanligste infeksjonene som førte til avslutning av behandling var HZ og pneumoni Profylaktisk zoster-vaksinering Vurderes til pasienter som har hatt RA over lengre tid og som tidligere har brukt to eller flere biologiske DMARD-er. Levende zoster-vaksine bør kun administreres til pasienter som tidligere har hatt vannkopper, eller er seropositive for varicella zoster virus (VZV). Dersom usikkert: teste for antistoffer mot VZV Levende vaksiner bør gis minst 2 uker før, men helst 4 uker før oppstart Xeljanz SPC in approval 10

11 5-year post-approval safety surveillance of tofacitinib: 3-year results from CORRONA, US-based RA registry New initiations Nov 6, 2012 May 31, 2016, ~3 years and 6 months Tofacitinib:874 bdmards:4904 csdmards: 1461 Kavanaugh et al. Poster presented (2595) at the American College of Rheumatology Annual Scientific Meeting, Washington DC, USA, November 11 16, 2016

12 5-year post-approval safety surveillance of tofacitinib: 3-year results from CORRONA, US-based RA registry New initiations Nov 6, 2012 May 31, 2016, ~3 years and 6 months Tofacitinib:874 bdmards:4904 csdmards: 1461 Kavanaugh et al. Poster presented (2595) at the American College of Rheumatology Annual Scientific Meeting, Washington DC, USA, November 11 16, 2016

13 5-year post-approval safety surveillance of tofacitinib: 3-year results from CORRONA, US-based RA registry Conclusion: Despite some differences in baseline characteristics (tofacitinib arm had longer disease duration and greater previous bdmard use), patients initiating tofacitinib, bdmards, and csdmards for the treatment of RA experienced comparable age- and gender-adjusted rates of serious infections, cardiovascular events, and malignancies overall. Kavanaugh et al. Poster presented (2595) at the American College of Rheumatology Annual Scientific Meeting, Washington DC, USA, November 11 16, 2016

14 Long-term efficacy of tofacitinib: ACR20, ACR50 and ACR70 (All Patients) 100 Tofacitinib 5 mg BID Tofacitinib 10 mg BID Tofacitinib all doses patients patient-years of experience over 8 years Patients, % ACR20 ACR50 ACR70 N 5 mg BID 10 mg BID Total Month Wollenhaupt J, Silverfield J, Lee EB, et al. Tofacitinib, an oral Janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and clinical and radiographic efficacy in open-label, longterm extension studies over 7 years. ACR/ARHP Annual Scientific Meeting; November 6-11, 2015, 2015; San Francisco, CA. ORAL Sequel, LTE study 1024, Table e2.1; Data as of January ACR50=American College of Rheumatology 50% response criteria; BID=twice daily; N=total number of patients.

15 Oppsummering Xeljanz (Tofacitinib) Små-molekylært (ikke-biologisk) legemiddel i tablett form Moderat til alvorlig aktiv RA i annen linje, mono/kombi Sikkerhet Sikkerhetsprofil, screening og oppfølging som eksisterende annen-linje behandling med unntak av HZ Effekt Som eksisterende annen-linje behandling ACR20/50/70 oppnåelse: « » ved oppstart « » i vedlikehold