Background:There is a lack of real-life evidence on secukinumab effectiveness in psoriatic arthritis (PsA) patients.Objectives:To assess the real-life 6- and 12-month secukinumab retention rates and proportions of patients in remission/low disease activity (LDA) overall, and by prior biologic disease-modifying anti-rheumatic drug (bDMARD)/targeted synthetic (ts)DMARD use.Methods:Data from PsA patients treated with secukinumab in routine care from 13 countries in the European Spondyloarthritis (EuroSpA) Research Collaboration Network were pooled. Patients started secukinumab ≥12 months before date of datacut. Crude and LUNDEX adjusted (crude value adjusted for drug retention) 28-joint Disease Activity index for PSoriatic Arthritis (DAPSA28) and 28-joint Disease Activity Score with CRP (DAS28CRP) remission and LDA rates were calculated. Group comparisons between b/tsDMARD naïve, 1 prior and ≥2 prior b/tsDMARD users were done with ANOVA, Kruskal-Wallis, Chi-square or Kaplan-Meier analyses with log-rank test, as appropriate.Results:A total of 1543 PsA patients were included (Table 1). b/tsDMARD naïve patients had shorter time since diagnosis, higher baseline disease activity, a higher proportion were men and a higher proportion achieved remission. Overall 6/12-month secukinumab retention rates were 86%/74% and significantly higher in b/tsDMARD naïve patients at 12, but not 6 months (Table 2, Figure). Overall, crude 6- and 12-month DAPSA28≤4/DAS28CRP<2.6 were achieved by 13%/34% and 11%/39% of the patients, respectively.Table 1.All patients (n=1543)b/tsDMARD naïve (n=287)1 prior b/tsDMARD (n=333)≥2 prior b/tsDMARDs (n=923)p *Age (years), mean (SD)52 (11)49 (12.3)51 (11)53 (11)<0.001Male, %42%49%46%39%0.003Years since diagnosis, mean (SD)9 (8)7 (8)8 (7)10 (8)<0.001Current smokers, %19%21%22%18%0.23CRP (mg/L), median (IQR)5 (2-12)7 (2-19)4 (2-8)5 (2-11)<0.001DAPSA28, median (IQR)26 (18-37)28 (19-38)22 (13-32)27 (19-38)<0.001DAS28CRP, median (IQR)4.2 (3.3-5.0)4.4 (3.5-5.2)3.8 (2.6-4.5)4.2 (3.4-5.0)<0.001*Comparisons across number of prior b/tsDMARD were done with ANOVA, Kruskal-Wallis or Chi-square test, as appropriateTable 2.MonthsAll patients (n=1543)b/tsDMARD naïve (n=287)1 prior b/tsDMARD (n=333)≥2 prior b/tsDMARDs (n=923)p *Secukinumab retention rate, % (95%CI)686% (84-87%)89% (86-93%)85% (81-89%)85% (82-87%)0.111274% (72-76%)81% (76-86%)76% (71-80%)72% (69-75%)0.006DAPSA28≤4 Crude613%25%11%11%<0.001 LUNDEX11%22%9%9%<0.001 Crude1211%22%11%8%<0.001 LUNDEX7%17%7%5%0.001DAS28CRP<2.6 Crude634%51%33%30%<0.001 LUNDEX29%45%27%24%<0.001 Crude1239%55%41%34%<0.001 LUNDEX26%41%27%21%<0.001DAPSA28 >4 and ≤14 Crude633%42%32%30%0.04 LUNDEX27%37%27%25%0.02 Crude1235%48%36%32%0.009 LUNDEX24%36%24%20%0.004DAS28CRP ≤3.2 Crude652%69%53%47%<0.001 LUNDEX43%61%45%38%<0.001 Crude1255%72%55%50%<0.001 LUNDEX37%54%37%32%<0.001*Comparisons across number of prior b/tsDMARDs were done with Kaplan-Meier with log-rank test or Chi-Square test, as appropriateConclusion:In this real-life study of 1543 patients with PsA in 13 European countries 12-month secukinumab retention was high, and significantly higher for b/tsDMARD naïve patients. Overall, a higher proportion of bionaïve than previous b/tsDMARD users achieved remission, regardless of remission criteria.Acknowledgments:Novartis and IQVIA for supporting the EuroSpA RCNDisclosure of Interests:Brigitte Michelsen Grant/research support from: Research support from Novartis, Consultant of: Consulting fees Novartis, Stylianos Georgiadis Grant/research support from: Novartis, Daniela Di Giuseppe: None declared, Anne Gitte Loft Grant/research support from: Novartis, Consultant of: AbbVie, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer and UCB, Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Heřman Mann: None declared, Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Kari Eklund Consultant of: Celgene, Lilly, Speakers bureau: Pfizer, Roche, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Sema Yilmaz: None declared, Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Cecilie Heegaard Brahe Grant/research support from: Novartis, Burkhard Moeller: None declared, Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Carlos Sánchez-Piedra: None declared, Lucie Nekvindova: None declared, Matija Tomsic: None declared, Nina Trokovic: None declared, Eirik kristianslund: None declared, Helena Santos Speakers bureau: AbbVie, Eli-Lilly, Janssen, Pfizer, Novartis, Thorvardur Love: None declared, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Yavuz Pehlivan: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene and GSK., Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis
Background:Tumor necrosis factor inhibitors (TNFi) have been available for more than a decade for treatment of spondyloarthrtitis (SpA). Secukinumab (SEC) represents a new mode of action, but few studies have compared outcomes in patients(pts) treated with SEC vs TNFi – and the optimal treatment strategy in routine care remains to be established. Comparative studies between SEC and adalimumab (ADA) are ongoing.Objectives:To describe baseline characteristics and compare 1-yr treatment retention of SEC vs TNFi (ADA/certolizumab pegol(CLZ)/etanercept(ETN)/golimumab(GOL)/infliximab(IFX)) in SpA-pts from 5 Nordic countries.Methods:Observational, prospective cohort study. Pts with SpA (ankylosing spondylitis/non-radiographic axial SpA/undifferentiated SpA) starting SEC or any TNFi during 2015-2018 were identified in clinical rheumatology registries of the Nordic countries. Baseline characteristics were retrieved. Country-specific data were pooled. 1-yr treatment retention of SEC vs TNFi was assessed through crude survival probability curves, retention rates and adjusted Cox regression analyses (ADA reference). Analyses were stratified by line of bDMARD and TNFi type.Results:In total, 10692 treatment courses (834 SEC, 9858 TNFi) in 7952 patients were included. SEC was rarely used as 1stbDMARD (Table 1), whereas it was the drug most frequently used as 3rd+ line (Table 2). Baseline characteristics were numerically similar for SEC vs TNFi (Table 1).Table 1.Patient characteristics at treatment start1stline2ndline3rd+ lineSECTNFiSECTNFiSECTNFiN70518615626056082067Male, %535544534546Age, yrs45 (14)41 (14)45 (12)44 (13)47 (12)46 (13)BASDAI, mm45 (28)53 (22)52 (22)52 (24)63 (22)58 (24)Concomitant csDMARD, %182723232726Means (SD) unless otherwise statedTable 2.Table 2. 1-yr treatment retention (Kaplan Meier, Cox Regression)DrugRetentions rates, 1 yr % (95% CI)Adjusted* HR (95% CI) for discontinuation1stlineADA76 (73-79)1CLZ68 (63-72)1.4 (1.1-1.8)ETN74 (71-76)1.1 (0.9-1.3)GOL80 (77-84)0.8 (0.6-1.0)IFX65 (62-67)1.5 (1.3-1.8)SEC76 (62-85)0.9 (0.5-1.6)2ndlineADA72 (68-75)1CLZ58 (51-64)1.5 (1.2-1.9)ETN65 (61-68)1.2 (1.0-1.5)GOL73 (67-77)0.9 (0.7-1.2)IFX67 (63-71)1.2 (0.9-1.5)SEC67 (58-74)1.1 (0.8-1.5)3rd+ lineADA73 (68-77)1CLZ52 (46-57)2.0 (1.6-2.6)ETN65 (61-70)1.3 (1.0-1.6)GOL65 (60-70)1.3 (1.0-1.7)IFX61 (56-66)1.5 (1.2-1.9)SEC61 (57-65)1.4 (1.1-1.8)* by sex, baseline age, BASDAI, concomitant csDMARD (y/n/missing). Pts with missing baseline BASDAI (41-60%) excluded1-yr treatment retention varied between the TNFi (Figure,Table 2), with SEC showing retention rates comparable to ADA when used as 1stor 2ndline therapy. However, SEC retention was poorer than ADA when used as 3rd+ therapy, but comparable to retention of other TNFi.In adjusted Cox regression analyses, confidence intervals were wide and included 1 for SEC vs ADA (1st, 2ndline), whereas there was slightly poorer retention of SEC versus ADA when used as 3rd+ bDMARD (Table 2).Conclusion:These observational data in >10.000 biological treatment courses in SpA, showed that SEC was mainly used in bDMARD experienced pts. Baseline characteristics were similar in pts treated with SEC vs TNFi. The 1-yr retention for SEC was similar to that of the TNFi when used as 1stor 2ndline, but poorer than ADA regarding 3rd+ courses. Further analyses are planned to explore confounding by indication and channeling towards treatment.Acknowledgments:Glintborg/Lindström shared 1st author, Kristensten/Jacobsson shared last.Partly funded by NordForsk and FOREUMDisclosure of Interests:Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Sella Aarrestad Provan Consultant of: Novartis, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Brigitte Michelsen Grant/research support from: Research support from Novartis, Consultant of: Consulting fees Novartis, Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Kalle Aaltonen: None declared, Anna-Mari Hokkanen Grant/research support from: MSD, Tanja Schjødt Jørgensen Speakers bureau: Abbvie, Pfizer, Roche, Novartis, UCB, Biogen, and Eli Lilly, Rebekka L. Hansen: None declared, Arni Jon Geirsson: None declared, Kathrine L. Grøn Grant/research support from: BMS, Niels Steen Krogh: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lars Erik Kristensen Consultant of: UCB Pharma (Advisory Board), Sannofi (Advisory Board), Abbvie (Advisory Board), Biogen (Advisory Board), Speakers bureau: AbbVie, Amgen, Biogen, Bristol-Myers Squibb,Celgene, Eli Lilly, Gilead, Forward Pharma, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer
Background:Knowledge of changes over time in baseline characteristics and tumor necrosis factor inhibitor (TNFi) response in bio-naïve axial spondyloarthritis (axSpA) patients treated in routine care is limited.Objectives:To investigate secular trends in baseline characteristics and retention, remission and response rates in axSpA patients initiating a first TNFi.Methods:Prospectively collected data on bio-naïve axSpA patients starting TNFi in routine care from 15 European countries were pooled. According to year of TNFi initiation, three groups were defined a priori based on bDMARD availability: Group A (1999–2008), Group B (2009–2014) and Group C (2015–2018). Retention rates (Kaplan-Meier), crude and LUNDEX adjusted1 remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <20) and response (ASDAS Major and Clinically Important Improvement (MI/CII), BASDAI 50) rates were assessed at 6, 12 and 24 months. No statistical comparisons were made.Results:In total, 27189 axSpA patients were included (5945, 11255 and 9989 in groups A, B and C).At baseline, patients in group A were older, had longer disease duration and a larger proportion of male and HLA-B27 positive patients compared to B and C, whereas disease activity was similar across groups.Retention rates at 6, 12 and 24 months were highest in group A (88%/81%/71%) but differed little between B (84%/74%/64%) and C (85%/76%/67%).In all groups, median ASDAS and BASDAI had decreased markedly at 6 months (Table 1). The ASDAS values at 12 and 24 months and BASDAI at 24 months were higher in group A compared with groups B and C. Similarly, crude remission and response rates were lowest in group A. After adjustments for drug retention (LUNDEX), remission and response rates showed less pronounced between-group differences regarding ASDAS measures and no relevant differences regarding BASDAI measures.Conclusion:Nowadays, axSpA patients initiating TNFi are younger with shorter disease duration and more frequently female and HLA-B27 negative than previously, while baseline disease activity is unchanged. Drug retention rates have decreased, whereas crude remission and response rates have increased. This may indicate expanded indication but also a stable disease activity threshold for TNFi initiation over time, an increased focus on targeting disease remission and more available treatment options.References:[1]Arthritis Rheum 2006; 54: 600-6.Table 1.Secular trends in baseline characteristics, treatment retention, remission and response rates in European axSpA patients initiating a 1st TNFiBaseline characteristicsGroup A(1999–2008)Group B(2009–2014)Group C(2015–2018)Age, years, median (IQR)57 (49–66)51 (42–60)46 (37–56)Male, %666057HLA-B27, %877772Years since diagnosis, median (IQR)5 (1–12)2 (0–8)2 (0–7)Smokers, %232425ASDAS, median (IQR)3.5 (2.8–4.1)3.4 (2.8–4.1)3.5 (2.8–4.1)BASDAI, median, (IQR)57 (42–71)59 (43–72)57 (41–71)TNFi drug, % (Adalimumab /Etanercept / Infliximab /Certolizumab / Golimumab)22 / 35 / 43 / 0 / 037 / 21 / 20 / 4 / 1827 / 28 / 24 / 8 / 13Follow up6 months12 months24 monthsGr AGr BGr CGr AGr BGr CGr AGr BGr CRetention rates, %, (95% CI)88 (88–89)84 (83–85)85 (84–86)81 (80–82)74 (74–75)76 (75–76)71 (70–72)64 (63–65)67 (66–68)ASDAS, median, (IQR)1.8 (1.2–2.8)1.9 (1.2–2.8)1.8 (1.2–2.6)1.9 (1.3–2.6)1.7 (1.2–2.5)1.6 (1.1–2.4)1.9 (1.4–2.6)1.7 (1.1–2.4)1.5 (1.1–2.2)ASDAS inactive disease, %, c/L28 / 2528 / 2430 / 2624 / 1932 / 2434 / 2623 / 1634 / 2039 / 23ASDAS CII, %, c/L57 / 5159 / 5063 / 5461 / 5063 / 4767 / 5159 / 4168 / 4074 / 45ASDAS MI, %, c/L31 / 2732 / 2737 / 3232 / 2637 / 2741 / 3130 / 2042 / 2546 / 28BASDAI, median, (IQR)23 (10–40)26 (11–48)24 (10–44)21 (10–38)23 (10–42)20 (8–39)22 (9–40)20 (8–39)16 (6–35)BASDAI remission, %, c/L44 / 4040 / 3443 / 3645 / 3645 / 3450 / 3844 / 3048 / 2956 / 34BASDAI 50 response, %, c/L53 / 4750 / 4253 / 4557 / 4656 / 4258 / 4457 / 3960 / 3563 / 38Gr, Group; c/L, crude/LUNDEX adjusted.Acknowledgements:Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network.Disclosure of Interests:Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Sara Nysom Christiansen Speakers bureau: BMS and GE, Grant/research support from: Novartis, Simon Horskjær Rasmussen: None declared, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Ulf Lindström: None declared, Jakub Zavada: None declared, Florenzo Iannone: None declared, Fatos Onen: None declared, Michael J. Nissen Speakers bureau: Novartis, Eli Lilly, Celgene, and Pfizer, Consultant of: Novartis, Eli Lilly, Celgene, and Pfizer, Brigitte Michelsen Consultant of: Novartis, Grant/research support from: Novartis, Maria Jose Santos Speakers bureau: AbbVie, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GlaxoSmithKline, Dan Nordström Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, Roche, UCB, Manuel Pombo-Suarez: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Egis, Novartis, Pfizer, UCB, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Irene van der Horst-Bruinsma Speakers bureau: Abbvie, BMS, MSD, Novartis, Pfizer, Lilly, UCB, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Johan Askling: None declared, Bente Glintborg Grant/research support from: Pfizer, Biogen, AbbVie, Karel Pavelka Speakers bureau: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Consultant of: AbbVie, Roche, MSD, UCB, Pfizer, Novartis, Egis, Gilead, Eli Lilly, Elisa Gremese: None declared, Nurullah Akkoc: None declared, Adrian Ciurea Speakers bureau: Abbvie, Eli-Lilly, MSD, Novartis, Pfizer, Eirik kristianslund: None declared, Anabela Barcelos: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene, Amgen, GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Carlos Sánchez-Piedra: None declared, Ruxandra Ionescu Speakers bureau: Abbvie, Amgen, Boehringer-Ingelheim Eli-Lilly,Novartis, Pfizer, Sandoz, UCB, Ziga Rotar Speakers bureau: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Biogen, Medis, MSD, Novartis, Pfizer, Marleen G.H. van de Sande: None declared, Arni Jon Geirsson: None declared, Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB and Wyeth, Merete L. Hetland Speakers bureau: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis.
Background:The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established.Objectives:The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess and compare other efficacy measures.Methods:The investigator-initiated NORD-STAR trial (NCT01491815) was conducted in the Nordic countries and Netherlands. In this multicenter, randomized, open-label, blinded-assessor study pts with treatment-naïve, early RA with DAS28>3.2, and positive RF or ACPA, or CRP >10mg/L were randomized 1:1:1:1. Methotrexate (25 mg/week after one month) was combined with: 1) (ACT): oral prednisolone (tapered quickly);or: sulphasalazine, hydroxychloroquine and mandatory intra-articular (IA) glucocorticoid (GC) injections in swollen joints <wk 20; 2) certolizumab 200 mg EOW SC (CZP); 3) abatacept 125 mg/wk SC (ABA); tocilizumab 162 mg/wk SC (TCZ). IA GC was allowed in all arms <wk 20. Primary outcome was clinical disease activity index remission (CDAI≤2.8) at wk 24. Secondary outcomes included CDAI remission over time and other remission criteria. Dichotomous outcomes were analyzed by adjusted logistic regression with non-responder imputation (NRI). Non-inferiority analyses had a pre-specified margin of 15%.Results:812 pts were randomized. Age was 54.3±14.7 yrs (mean±SD), 31.2% were male, DAS28 5.0±1.1, 74.9% were RF and 81.9% ACPA positive. Fig 1 shows the adjusted CDAI remission rates over time with 95% CI. Table shows crude remission and response rates and absolute differences in adjusted remission and response rates (superiority analysis). Differences in remission and response rates with CZP and TCZ, but not with ABA, remained within the pre-defined non-inferiority margin versus ACT, Fig 2.Figure 1.CDAI remission over time (adj. estimates with 95% CI)Figure 2.Non-inferiority analysis of protocol population. Estimated differences in CDAI remission rates between Arm 1 (active conventional therapy) and Arms 2, 3, and 4 (biologic arms) as reference with 95% confidence intervals, adjusted for gender, ACPA status, country, age, body-mass index and baseline DAS28-CRP. ABA, abatacept; CZP, certolizumab-pegol; MTX, methotrexate; TCZ, tocilizumab.Conclusion:High remission rates were found across all four treatment arms at 24 wks. Higher CDAI remission rate was observed for ABA versus ACT (+9%) and for CZP (+4%), but not for TCZ (-1%). With the predefined 15% margin, ACT was non-inferior to CZP and TCZ, but not to ABA. This underscores the efficacy of active conventional therapy based on MTX combined with glucocorticoids and may guide future treatment strategies for early RA.Table.Primary and key secondary outcomes at 24 weeks (ITT)Active conventional therapy (ACT)Certolizumab+MTXAbatacept+MTXTocilizumab+MTXNo of pts (ITT)200203204188§Crude remission and response ratesCDAI remission42.0%47.8%52.5%41.0%ACR/EULAR Boolean remission34.0%38.4%37.3%31.4%DAS28 remission63.5%68.5%69.6%63.3%SDAI remission41.5%49.8%51.5%42.6%EULAR good response71.5%76.9%79.9%71.3%Difference (95% CI) in rates with Arm 1 as reference (adjusted)CDAI remissionRef4% (-5 to 13%)9% (0.1 to 19%)-1% (-10 to 9%)ACR/EULAR Boolean remissionRef4% (-6 to 13%)5% (-5 to 14%)-4% (-13 to 6%)DAS28 remissionRef3% (-6 to 11%)5% (-4 to 13%)-1% (-10 to 8%)SDAI remissionRef6% (-3 to 18%)9% (-0.3 to 18%)1% (-8 to 11%)EULAR good responseRef4% (-4 to 14%)8% (-2 to 18%)0.4% (-10 to 11%)§17 patients allocated to Tocilizumab did not receive it due to its unavailability and were excluded from ITT.Acknowledgments:Manufacturers provided CZP and ABA.Disclosure of Interests:Merete L. Hetland Grant/research support from: BMS, MSD, AbbVie, Roche, Novartis, Biogen and Pfizer, Consultant of: Eli Lilly, Speakers bureau: Orion Pharma, Biogen, Pfizer, CellTrion, Merck and Samsung Bioepis, Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD, Anna Rudin Consultant of: Astra/Zeneca, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Jon Lampa Speakers bureau: Pfizer, Janssen, Novartis, Kim Hørslev-Petersen: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Gerdur Gröndal: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Marte Heiberg: None declared, Jos Twisk: None declared, Simon Krabbe: None declared, Kristina Lend: None declared, Inge Olsen: None declared, Joakim Lindqvist: None declared, Anna-Karin H Ekwall Consultant of: AbbVie, Pfizer, Kathrine L. Grøn Grant/research support from: BMS, Meliha C Kapetanovic: None declared, Francesca Faustini: None declared, Riitta Tuompo: None declared, Tove Lorenzen: None declared, Giovanni Cagnotto: None declared, Eva Baecklund: None declared, Oliver Hendricks Grant/research support from: Pfizer, MSD, Daisy Vedder: None declared, Tuulikki Sokka-Isler: None declared, Tomas Husmark: None declared, Maud-Kristine A Ljosa: None declared, Eli Brodin: None declared, Torkell Ellingsen: None declared, Annika Soderbergh: None declared, Milad Rizk Speakers bureau: AbbVie, Åsa Reckner: None declared, Per Larsson: None declared, Line Uhrenholt Speakers bureau: Abbvie, Eli Lilly and Novartis (not related to the submitted work), Søren Andreas Just: None declared, David Stevens: None declared, Trine Bay Laurberg Consultant of: UCB Pharma (Advisory Board), Gunnstein Bakland Consultant of: Novartis, UCB, Ronald van Vollenhoven Grant/research support from: BMS, GSK, Lilly, UCB, Pfizer, Roche, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Janssen, Pfizer, Servier, UCB, Speakers bureau: AbbVie, Pfizer, UCB
BackgroundThe MBDA score, based on 12 serum proteins, is a validated tool for assessing disease activity in RA patients. MBDA biomarkers may be influenced by age, sex and adiposity.ObjectivesTo develop and validate an adjusted MBDA score that accounted for these three factors, using BMI or serum leptin as proxies for adiposity.MethodsThe MBDA score as a continuous variable was adjusted to account for age, sex and a proxy for adiposity (serum leptin) using data from 325,781 RA patients for whom MBDA tests had been ordered as part of routine care. Leptin values came from the MBDA test. As an alternative to using leptin to adjust for adiposity, a cohort of 1411 patients from 5 studies/registries (BRASS, Corrona-CERTAIN, InFoRM, OPERA, RACER) was used to adjust for BMI, which was not available in the larger cohort, adding this BMI adjustment to that for age/sex from the larger cohort. Both types of adjusted MBDA score use the low, moderate, and high disease activity cutpoints of the original MBDA score. The two adjusted MBDA scores and other variables were evaluated for the prediction of radiographic progression (RP) in the 2 cohorts with available data (OPERA, BRASS) using univariate and multivariate linear regression analyses. Rate of RP was assessed as the change in modified total Sharp score (ΔmTSS) per year after MBDA testing.ResultsThe MBDA score increased with age, BMI and leptin concentration. In univariate analysis of the combined OPERA and BRASS cohorts (n=555), the significant variables predicting ΔmTSS were leptin-adjusted MBDA score, seropositivity for RF or anti-CCP, BMI-adjusted MBDA score, MBDA score, BMI, CRP, baseline mTSS, disease duration, DAS28-CRP, SDAI, CDAI and DAS28* (table 1). The leptin- and BMI-adjusted MBDA scores were the first and third most significant univariate predictors of ΔmTSS. To compare them directly, DAS28-CRP, MBDA score, BMI-adjusted MBDA score and leptin-adjusted MBDA score were combined in pairs in regression analyses of ΔmTSS; the BMI-adjusted (p=0.0027) and leptin-adjusted MBDA score were significant (p=0.00063) after adjusting for DAS28-CRP (p=0.87 and 0.74, respectively) and the leptin-adjusted MBDA score was significant (p=0.024 and 0.020, respectively) after adjusting for either the MBDA (p=0.32) or BMI-adjusted MBDA scores (p=0.094).Abstract AB0244 – Table 1Univariate Linear Regression Analysis of the Association of Clinical and Laboratory Variables with ΔmTSS in the OPERA and BRASS Combined CohortConclusionsWe developed two adjusted MBDA scores that combine molecular and biometric variables to account for age, sex, and adiposity. The leptin-adjusted MBDA score, significantly outperformed DAS28-CRP and the original MBDA score in predicting radiographic progression in RA patients. These results suggest that the leptin-adjusted MBDA score may offer improved clinical utility for the personalised management of patients with RA.Disclosure of InterestJ. Curtis Grant/research support from: Crescendo Bioscience Inc., Consultant for: Crescendo Bioscience Inc., D. Flake II Sha...
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