Ταχύτητα Δράσης των βιολογικών παραγόντων. Γκίκας Κατσιυής MD, PhD, RhMSUS Διεσθσντής Ρεσματολογικής Κλινικής Ναστικού Νοσοκομείοσ Αθηνών

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1 Ταχύτητα Δράσης των βιολογικών παραγόντων Γκίκας Κατσιυής MD, PhD, RhMSUS Διεσθσντής Ρεσματολογικής Κλινικής Ναστικού Νοσοκομείοσ Αθηνών

2 ύγκροσση σσμυερόντων Ακνηβή γηα ηελ παξνπζίαζε από ηε UCB Εθπαηδεπηηθέο-εξεπλεηηθέο-ζπκβνπιεπηηθέο επηρνξεγήζεηο ηελ ηειεπηαία δηεηία: MSD, Abbvie, Novartis, BMS, UCB, Roche

3 1 ο Περιστατικό Πιήξσκα ειηθνπηέξνπ (αεξνλαπηίινο), εηώλ 32 Φσξηαζηθό εμάλζεκα ηξηρσηνύ θεθαιήο θαη άθξσλ Πξστλή δπζθακςία ύγθακςε ΔΕ αγθώλα Αξζξίηηδα ΜΚΦ άκθσ Δαθηπιίηηδα ΔΕ δείθηε Μεξηθή αληαπόθξηζε ζε ΜΣΥ

4 2 ο Περιστατικό Μέινο ΟΤΚ, 28 εηώλ Έληνλε πξστλή δπζθακςία Άιγνο ηεξνιαγνλίσλ άκθσ ηεξλνπιεπξηθή ρνλδξίηηδα Αξζξίηηδα ΔΕ ΠΥΚ Μεξηθή αληαπόθξηζε ζε NSAIDs

5 2 ο Περιστατικό

6 Θεραπεία και Γρήγορα αποτελέσματα

7 Anti-TNFα

8 Infliximab in the treatment of AS Improvement >50% in BASDAI Braun J et al Ann Rheum Dis 2005

9 Adalimumab in PsA Genovese M. et al. Journal of Rheum. 2007

10 ATLAS (Adalimumab Trial for Long-Term Efficacy and Safety in AS) ASAS 20 Van der Heijde et al Arthr. Rheum. 2006

11 Abatacept (prevents costimulatory binding)

12 Ποσοστά ασθενών (%) AMPLE - RA MTX-IR, SC abatacept vs. adalimumab ACR ανταποκρίσεις Abatacept SC Adalimumab ACR 20 ACR 50 ACR 70 ACR % 59.7% 46.6% 44.7% 31.1% 29.3% 14.5% 8.2% Ημέρα επίσκεψης Schiff M, et al. Ann Rheum Dis 2014

13 Εtanercept - Improvement in disability of RA pts 95% 90% 85% 80% 75% 70% 65% 60% 55% 50% % achieving minimal clinically important difference, MCID = ΔHAQ 0.22 % achieving MCID - early RA % achieving MCID - established RA 66% 52% 73% 59% 83% 70% Week 2 Month 1 Month 3 Year 3 85% 75% Baumgartner SW et al. Journal of Rheum. 2004

14 Patients (%) Etanercept (EMBARK study) proportion of nr-axspa patients achieving ASAS40 ASAS40 response at week 12 and Double blind Open label 51, , ,6 33,3 38, ETN/ETN 15,2 15,7 14,8 PBO/ETN 3,8 14, Weeks (n = 105) (n = 108) Dougados M, et al. Arth Rheum 2014

15 Golimumab σε nr-axspa GO-AHEAD Sieper J. et al. Arthritis Rheum 2015

16 Tocilizumab (anti IL-6R)

17 ADACTA: Monotherapy treatment with either tocilizumab or adalimumab

18 ADACTA

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20 Ustekinumab in PsA, PSUMMIT I ACR20 McInnes et al. Lancet 2013

21 Αναστολείς IL-17 στη θεραπεία της Α, ΨΑ

22 Percentage of Responders Secukinumab in PsA, FUTURE 2 ACR Primary endpoint 54.0% 51.0% 29.3% 15.3% Secukinumab 300 mg Secukinumab 150 mg Secukinumab 75 mg Placebo 72.7% 72.7% 66.7% Weeks McInnes IB, et al. Lancet 2015

23 Secukinumab in AS Baeten D. et al NJM 2015

24 Certolizumab, Fc-free, PEGylated Anti-TNF Cimzia Structure Fab PEG Cimzia Feature Only PEGylated anti-tnf Observed effects Clinical Hypothesis Ongoing research Increased half life (14 days) and hydrosolubility with reduced mast cell degranulation (in vitro), compared to the non-pegylated protein May explain observed enhanced penetration of Cimzia, as compared to Humira and Remicade, into inflamed tissues in animal models A clinical study with radiolabelled Cimzia demonstrated rapid uptake into inflamed joints; in 4 case studies, Cimzia treatment of TNF-resistant patients resulted in fast clinical resolution of oligoarthritis 18 Enhanced tissue penetration 5 Distribution of Tc99m radiolabelled Cimzia in the hands of a patient with dactylitis of the 4 th digit of the left hand Only anti- TNF with no Fc region Avoidance of Fc-mediated effects such as complement- or antibody-dependent cytotoxicity Longer residency in inflamed tissues Only univalent anti-tnf Cimzia does not cross-link antigens to form large immune complexes, which can cause neutrophil degranulation, superoxide production (in vitro), and increased clearance Small immune complexes mount less significant immune responses than larger complexes and prolong sustainability Exxelerate Pasut G. Biodrugs Palframan R et al. J Immunol Methods Shim H. Exp Mol Med Carron P et al. Arthritis Rheum Schouwenburg P et al. Nat Rev Rheum. 2013

25 Rapid Induction of Response for Patients with a Loading Dose PK Profile of a Typical 70 kg RA Subject Derived from the Population PK Model Cimzia concentration (μg/ml) Time (weeks) Lacroix B et al. Clin Pharm Ther. 2009

26 Responders (%) Rapid ACR Responses in Certolizumab pegol-treated RA Patients by Week 1 RAPID Placebo + MTX (n=199) Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W + MTX (n=393) ACR20 1 ACR50 2 ACR Week Keystone E et al. Arthr. Rheum. 2008

27 Improvement Mean Change from Baseline Rapid Improvements in Pain from Week 1 Mean change from Baseline in pain (PtAAP-VAS) at Week 1 in certolizumab pegol-treated RA patients (RAPID 1) Actual Baseline Scores n , ,9 Placebo Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W + MTX Strand V et al. Arthritis Res Ther. 2009

28 Improvement Mean Change in DAS28(CRP) from Baseline Rapid Improvements in Disease Activity in Certolizumab-pegol-treated PsA Patients by Week 1 0 Placebo (n=136) Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W (n=138) Weeks

29 Rapid Improvements in Pain from Week 1 Mean change from Baseline in pain (PtAAP-VAS) at Week 1 in PsA patients (RAPID-PsA) Mean Change from Baseline 2 Improvement Actual Baseline Scores n ,4-9,2 Placebo Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W Gladman D et al. Arthritis Care Res. 2014

30 Improvement Rapid Improvements in Disease Activity in axspa with certolizumab pegol by Week 1 Mean BASDAI score in overall axspa, AS and nr-axspa subpopulations 7 axspa PBO (n=106) AS Cimzia combined dose (n=121) AS PBO (n=57) axspa Cimzia combined dose (n=218) nr-axspa Cimzia combined dose (n=97) nr-axspa PBO (n=50) 6 Mean BASDAI Score Week Sieper J et al. Arthritis Rheumatol Landewé R et al. Ann Rheum Dis. 2014

31 Improvement Mean Change from Baseline 1 0 Rapid Improvements in noctural pain from Week 1 Mean change from Baseline in nocturnal back pain at Week 1 in certolizumab pegol-treated axspa patients (RAPID-axSpA) Actual Baseline Scores n ,5-1 -0,6-1,5-2 -2,5-3 -1,9 Placebo Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W Sieper J et al. Arthritis Care & Res

32 Improvement Mean Change in Daily Pain from Baseline Rapid Improvements in daily pain from Day 2 Mean change from Baseline in daily pain to day 7 in certolizumab pegol-treated axspa patients (RAPID-axSpA) 0 Placebo (n=100) Cimzia 400 mg at Weeks 0, 2 and 4 followed by Cimzia 200 mg Q2W (n=110) Days Sieper J et al. Arthritis Care Res. 2015

33 Exxelerate: First Blinded Randomised Head-to-Head Superiority Study Within the Anti-TNF Class Objective To evaluate the short- and long-term efficacy of Cimzia compared with Humira, both in combination with MTX, in the treatment of moderate to severe RA that is not responding adequately to MTX Inclusion Criteria: RA patients with an inadequate response to MTX Biologic-naïve Positive RF and/or anti-ccp Moderate to severe RA: 4 swollen joints DAS28(ESR) >3.2 CRP 10 mg/l or ESR 28 mm/hr Cimzia LD followed by Cimzia 200 mg Q2W + MTX 2 n=916 1:1 randomisation (no stratification) Humira 40 mg Q2W + MTX 3 Week 12 responders Cimzia 200 mg Q2W + MTX Week 12 non-responders Humira 40 mg Q2W + MTX Week 12 responders Humira 40 mg Q2W + MTX Week 12 non-responders Cimzia LD (at Weeks 12, 14, 16) followed by Cimzia 200mg Q2W + MTX Cimzia completers Cimzia Humira switchers Humira completers Humira Cimzia switchers Primary Endpoints % with ACR20 response at Week 12 % with DAS28(ESR) 3.2 at Week 104 Week

34 σμπερασματικά Οη βηνινγηθνί παξάγνληεο εκθαλίδνπλ ηαρεία έλαξμε δξάζεο θαη απνηειεζκαηηθόηεηαο ζηε Ρεπκαηνεηδή αζξίηηδα θαη ηηο πνλδπιναξζξίηηδεο ήδε από ηε 2 ε εβδνκάδα. Σν certolizumab pegol εκθαλίδεη δεδνκέλα απνηειεζκαηηθόηεηαο από ηελ 1 ε εβδνκάδα. Αλάγθε ύπαξμεο πεξηζζόηεξσλ δεδνκέλσλ από άκεζε ζύγθξηζε (Head-to-head comparison).

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