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BackgroundEvidence demonstrates sex differences in disease presentation, physical function, treatment response and drug retention in patients with psoriatic arthritis (PsA). Data from observational cohort studies indicate female sex is associated with reduced effectiveness of tumor necrosis factor inhibitors (TNFis)1,2. Although, conflicting results are also reported3,4. We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice.ObjectivesTo investigate sex differences in treatment response and drug retention rates in clinical practice among patients with PsA, treated with their first TNFi.MethodsData from biologic-naïve PsA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on low disease activity (LDA) according to DAS28-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on LDA. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (ResultsIn total, 7,679 PsA patients with available data on DAS28-CRP at 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have LDA was 17% (RR, 0.83; 95% confidence interval [CI], 0.81 to 0.85) lower compared to males and the difference in probability for having LDA was 13 percentage points (RD, 0.13; 95% CI, 0.11 to 0.15). The survival analysis included 18,599 PsA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/68%/56%) compared to males (89%/80%/69%), see Figure 1.Table 1.Baseline characteristics of all biologic-naïve PsA patients treated with their first TNFi and available DAS28-CRP at 6 month, data pooled across all countriesFemaleMaleMean (SD), median [IQR] or percentagesMean (SD), median [IQR] or percentagesAge (years)49.7 (12.5)47.8 (11.9)Disease duration (years)4.0 [1.0, 10.0]4.0 [1.0, 10.0]TNFi start year 1999-200929%29% 2010-201326%27% 2014-201625%24% 2017-202020%20%Concomittant csDMARD75%77%DAS28-CRP4.4 (1.2)4.2 (1.2)DAPSA2832 (16)29 (16)CRP (mg/L)7.0 [3.0, 17.0]8.0 [3.3, 19.0]SJC (0-28)3.0 [1.0, 6.0]3.0 [1.0, 6.0]TJC (0-28)6.0 [2.0, 10.0]4.0 [2.0, 9.0]VAS pain, mm61 (23)55 (23)VAS fatigue, mm62 (26)53 (27)Data are as observed, mean (SD), median [IQR] or percentage. TNFi, tumor necrosis factor inhibitor; csDMARD, Conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP, Disease Activity Score 28-joint count C reactive protein; DAPSA28, Disease Activity in PsA 28; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count.ConclusionTreatment efficacy and retention rates are lower among female patients with PsA initiating their first TNFi. Females presented with higher 28-tender joint count and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education.References[1]Højgaard, et al. Rheumatology (Oxford). 2018 Sep 1;57(9):1651-1660.[2]Vieira-Sousa, et al. J Rheumatol. 2020 May 1;47(5):690-700.[3]Kristensen, et al. Ann Rheum. Dis. 2008 Mar;67(3):364-9.[4]Iervolino, et al. J Rheumatol. 2012 Mar;39(3):568-73.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsPasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Abbvie, Eli Lily, Novartis, UCB, Grant/research support from: Novartis, Janssen, UCB and Eli Lilly, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Thomas Klausch: None declared, Nina Trokovic: None declared, Tuulikki Sokka-Isler Consultant of: Abbvie, Amgen, BMS, Celgene, DiaGraphIT, Medac, MSD, Novartis, Orionpharma, Pfizer, Roche, Sandoz, and UCB, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Elsa Vieira-Sousa Speakers bureau: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Consultant of: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Grant/research support from: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly and Novartis, Brigitte Michelsen Grant/research support from: Novartis, Burkhard Moeller Speakers bureau: MSD, Synergy, Eli Lilly, Bristol-Myers-Squibb, Janssen-Cilag, AbbVie and Pfizer, Raphael Micheroli: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Corina Mogosan Speakers bureau: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Karin Laas Speakers bureau: Amgen, Janssen, Novartis and Abbvie, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Karen Minde Fagerli: None declared, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Isabel Castrejon Speakers bureau: Lilly, BMS, Janssen, MSD and Abbvie, Consultant of: Lilly, BMS, Janssen, MSD and Abbvie, Manuel Pombo-Suarez Consultant of: Abbvie, MSD and Roche, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Consultant of: Amgen and Novartis, Thorvardur Love: None declared, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche and AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche and AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Gökçe Kenar: None declared, Handan Yarkan-Tuğsal: None declared, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB

BackgroundEvidence reveals sex differences in physiology, disease presentation and response to treatment in axial spondyloarthritis (axSpA). Pooled data from four randomized controlled trials demonstrated reduced treatment efficacy of a tumor necrosis factor inhibitor (TNFi) in females compared to males with ankylosing spondylitis1. However, real-life evidence confirming these data in large cohorts is scarce. We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice.ObjectivesTo investigate sex differences in treatment response and drug retention rates in clinical practice among patients with axSpA, treated with their first TNFi.MethodsData from biologic-naïve axSpA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on clinically important improvement (CII) according to ASDAS-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on CII. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (ResultsIn total, 6,451 axSpA patients with available data on ASDAS-CRP at baseline and 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have CII was 15% (RR, 0.85; 95% confidence interval [CI], 0.82 to 0.89) lower compared to males and the difference in probability for having CII was 9.4 percentage points (RD, 0.094; 95% CI, 0.069 to 0.12). The survival analysis included 28,608 axSpA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/69%/58%) compared to males (89%/81%/72%), see Figure 1.Table 1.FemaleMaleMean (SD), Median [IQR] or percentagesMean (SD), Median [IQR] or percentagesAge (years)42.0 (12.1)41.4 (12.3)Fulfilment of mNYC66%80%Disease duration (years)2.0 [1.0, 7.0]3.0 [1.0, 9.0]TNFi start year Start 1999-20097.2%9.8% Start 2010-201326%27% Start 2014-201637%36% Start 2017-202030%27%BASDAI, mm59 (20)54 (21)BASFI, mm48 (25)46 (24)ASDAS, units3.5 (0.9)3.5 (1.0)CRP (mg/L)6.7 [2.5, 16.0]11.9 [4.0, 25.0]SJC (0-28)0 [0, 0]0 [0, 0]TJC (0-28)0 [0, 2]0 [0, 1]VAS pain, mm63 (22)59 (24)VAS fatigue, mm65 (25)59 (26)mNYC, modified New York criteria; TNFi, tumor necrosis factor inhibitor; BASDAI, Bath Ankylosing Spondylitis Disease Activity Indexf; BASFI, Bath Ankylosing Spondylitis Functional Index; ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale.ConclusionTreatment efficacy and retention rates are lower among female patients with axSpA initiating their first TNFi. Females presented with lower C-reactive protein levels and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education.References[1]van der Horst-Bruinsma et al. Ann Rheum Dis. 2013 Jul;72(7):1221-4.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsPasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Abbvie, Eli Lily, Novartis and UCB, Grant/research support from: Novartis, Janssen, UCB and Eli Lilly, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Thomas Klausch: None declared, Michael Nurmohamed Speakers bureau: Abbvie, Janssen and Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB and speaker fees from Abbvie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB, Grant/research support from: BMS, GSK and UCB, Dan Nordström Consultant of: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Anna-Mari Hokkanen Grant/research support from: MSD, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Elsa Vieira-Sousa Speakers bureau: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Consultant of: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Grant/research support from: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Anne Gitte Loft Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie and BMS, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene and Novartis, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly and Novartis, Brigitte Michelsen Grant/research support from: Novartis, Adrian Ciurea Speakers bureau: AbbVie and Novartis, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Corina Mogosan Speakers bureau: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Gary Macfarlane Grant/research support from: GSK, Gareth T. Jones Grant/research support from: AbbVie, Pfizer, UCB, Amgen and GSK, Karin Laas Speakers bureau: Amgen, Janssen, Novartis and Abbvie, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Isabel Castrejon Speakers bureau: Eli Lilly, BMS, Janssen, MSD and Abbvie, Consultant of: Eli Lilly, BMS, Janssen, MSD and Abbvie, Manuel Pombo-Suarez Consultant of: Abbvie, MSD and Roche, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Consultant of: Amgen and Novartis, Arni Jon Geirsson: None declared, Eirik kristianslund: None declared, Jiří Vencovský Speakers bureau: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Consultant of: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Lucie Nekvindova: None declared, Semih Gulle: None declared, Berrin Zengin: None declared, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB.

BackgroundIn axial spondyloarthritis (axSpA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a key patient-reported outcome. However, one or more of its components may be missing when recorded in clinical practice.ObjectivesTo determine whether an individual patient’s BASDAI at a given timepoint can be reliably calculated with different single imputation techniques and to explore the impact of the number of missing components and/or differences between missingness of individual components.MethodsReal-life data from axSpA patients receiving tumour necrosis factor inhibitors (TNFi) from 13 countries in the European Spondyloarthritis (EuroSpA) Research Collaboration Network were utilized [1]. We studied missingness in BASDAI components based on simulations in a complete dataset, where we applied and expanded the approach of Ramiro et al. [2]. After introducing one or more missing components completely at random, BASDAI was calculated from the available components and with three different single imputation techniques: possible middle value (i.e. 50) of the component and mean and median of the available components. Differences between the observed (original) and calculated scores were assessed and correct classification of patients as having BASDAIResultsA total of 19,894 axSpA patients with at least one complete BASDAI registration at any timepoint were included. 59,126 complete BASDAI registrations were utilized for the analyses with a mean BASDAI of 38.5 (standard deviation 25.9). Calculating BASDAI from the available components and imputing with mean or median showed similar levels of agreement (Table 1). When allowing one missing component, >90% had a difference of ≤6.9 mm between the original and calculated scores and >95% were correctly classified as BASDAI90% (Figure 1, upper panels). As expected, it was observed that regardless of the BASDAI component set to missing and the imputation technique used, correct classification of patients as BASDAITable 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAILevel of agreement with Dif≤6.9 mm* (%)Correct classification for BASDAI1 missing componentAvailable93.996.9Value 5073.996.3Mean94.296.8Median93.196.82 missing componentsAvailable83.794.8Value 5040.792.8Mean83.594.8Median82.894.73 missing componentsAvailable71.992.6Value 5028.187.3Mean72.292.6Median69.792.2* The levels of agreement with a difference (Dif) of ≤6.9 mm between the original and calculated scores were based on the half of the smallest detectable change. Agreement of >90% was considered as acceptable. ** Correct classification of >95% was considered as acceptable.Figure 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAIConclusionBASDAI calculation with available components gave similar results to single imputation of missing components with mean or median. Only when missing one of BASDAI components 5 or 6, single imputation techniques can reliably calculate individual BASDAI scores. However, missing any single component value results in misclassification of patients with original BASDAI scores close to 40.References[1]Ørnbjerg et al. (2019). Ann Rheum Dis, 78(11), 1536-1544.[2]Ramiro et al. (2014). Rheumatology, 53(2), 374-376.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsStylianos Georgiadis Grant/research support from: Novartis, Myriam Riek Grant/research support from: Novartis, Christos Polysopoulos Grant/research support from: Novartis, Almut Scherer Grant/research support from: Novartis, Daniela Di Giuseppe: None declared, Gareth T. Jones Speakers bureau: Janssen, Grant/research support from: AbbVie, Pfizer, UCB, Amgen, GSK, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Simon Horskjær Rasmussen Grant/research support from: Novartis, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Merih Birlik: None declared, Ayten Yazici Grant/research support from: Roche, Brigitte Michelsen Grant/research support from: Novartis, Eirik kristianslund: None declared, Adrian Ciurea Speakers bureau: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Ana Maria Rodrigues Speakers bureau: Abbvie, Amgen, Consultant of: Abbvie, Amgen, Grant/research support from: Novartis, Pfizer, Amgen, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, UCB, Viatris, Consultant of: Abbvie, Celgene, Pfizer, UCB, Viatris, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Corina Mogosan: None declared, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Björn Gudbjornsson Speakers bureau: Amgen, Novartis, Consultant of: Amgen, Novartis, Arni Jon Geirsson: None declared, Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Consultant of: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Grant/research support from: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Isabel Castrejon: None declared, Manuel Pombo-Suarez Consultant of: Abbvie, MSD, Roche, Bruno Frediani: None declared, Florenzo Iannone Speakers bureau: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis

BackgroundThe recently presented “ORAL Surveillance Study” has suggested increased risk of serious adverse events (AEs) with tofacitinib, a JAK-inhibitor (JAKi), compared to a comparator TNF-inhibitor (TNFi). Currently, there is limited real world evidence for the tolerability and safety of JAKi (1).ObjectivesTo assess the safety of JAKi compared to other biologic agents in rheumatoid arthritis (RA) patients in a real-world population, by evaluating treatment discontinuation for AEs.MethodsPooled patient database from 16 national RA registries from across Europe, Québec (Canada), Turkey, and Israel were used. Treatment discontinuation due to AEs by treatment groups, JAKi versus (vs) TNFi and JAKi vs bDMARDs with other modes of action (OMA), were compared as an overall measure of tolerability and safety of JAKi. Standard descriptive statistics were used for baseline characteristics. We plotted unadjusted cumulative incidence, then the cause-specific Cox model was used to account for competing risks, and to obtain association between covariates and the instantaneous hazard rate for AEs. Variables listed in Table 1 were used for adjustment in the fully-adjusted cause-specific Cox model.Table 1.Baseline characteristics of the study populationJAKi1(BARI, FILGO,TOFA,UPA)OMA2(ABA, ANAK, SARI, TOCI)TNFi3(ADA, CERT, ETAN, GOL, INFL)n = 9208n = 16737n = 64533Treatment duration* (yrs)0.7 [0.2, 1.7]1.1 [0.4, 2.8]1.5 [0.5, 3.9]Age57.556.853.2Female (%)81.380.773.2Disease duration (yrs)9.913.110.7Seropositivity (%)78.775.969.8Previous b/tsDMARD (%) 034.030.859.7 120.925.924.3 216.621.710.4 3 or more28.521.55.6Concomitant GC (%)44.650.741.3Concomitant CsDMARD (%) MTX22.622.028.8 MTX + other9.59.713.1 None50.552.543.5 Other17.415.914.7CRP13.2 (24.1)13.3 (25.6)12.3 (24.1)CDAI23.7 (13.8)22.9 (13.5)22.6 (14.0)DAS 284.7 (1.5)4.7 (1.6)4.6 (1.6)HAQ1.2 (0.7)1.2 (0.7)1.1 (0.7)BMI27.1 (5.9)26.8 (5.8)26.8 (5.8)Patients with at least one Comorbidity (%)51.753.949.6csDMARDs = classical synthetic DMARDs, MTX = methotrexate, GC = glucocorticoids, CRP = C-reactive protein, CDAI = Clinical Disease Activity Index, DAS 28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, BMI = Body Mass Index, *Treatment duration (median [IQR]) = Last visit date – start date (if treatment is ongoing), treatment stop date – treatment start date (if treatment has stopped). 1BARI (baricitinib; 44.41 %), FILGO (filgotinib; 0.23%), TOFA (tofacitinib; 49.59%), UPA (upadacitinib; 5.78%); 2ABA (abatacept; 39.96%), ANAK (anakinra; 2.64%), SARI (sarilumab; 3.14%), TOCI (tocilizumab; 52.55%); 3ADA (adalimumab; 31.00%), CERT (certolizumab; 8.33%), ETAN (etanercept; 38.83%), GOLI (golimumab; 9.36%), INFL (infliximab; 12.56%)Results90,478 treatment courses were included in the analysis (Table 1). We observed similar crude incidence rate of treatment discontinuation due to AEs between JAKi and TNFi, but less in JAKi vs OMA (Figure 1). The fully adjusted hazard rate of treatment stop for AEs was also similar in JAKi vs TNFi (HR = 1.02 (95% CI 0.92 – 1.13)), and in JAKi vs OMA (HR= 1.08 (95% CI 0.97 – 1.20)). The rate of treatment stop for AEs was higher in women (HR = 1.29 (95% CI 1.21 – 1.37)) and with an increasing number of previous b/tsDMARDs (HR = 1.50; 1.48; 1.68 for 1, 2, and 3 or more previous b/ts DMARDs, respectively).Figure 1.Comparison of cumulative incidence of treatment discontinuation for adverse events in JAKi, TNFi, and OMA groupConclusionAfter adjusting for potential confounders, the rate of treatment discontinuation for AEs was comparable between JAKi and OMA or TNFi. Treatment discontinuation for AEs comprises a wide range of AEs; future analyses will be performed to investigate specific AEs, such as cancer, serious infections or major adverse cardiovascular events.References[1]Ann Rheum Dis 2022. doi: 10.1136/annrheumdis-2021-221915.Disclosure of InterestsEric Nham: None declared, Romain Aymon: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Speakers bureau: DC reports speaker or consultant fees from Abbvie, Amgen, Eli Lilly, Fresenius-Kabi,Pfizer, Novartis, Sandoz, Tevapharm, Consultant of: Stated above, Catalin Codreanu Speakers bureau: CC reports speaker/consulting fees from AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Richter, Consultant of: Stated above, Ori Elkayam Consultant of: OE has received consultant and honorary fees from Pfizer, Lilly, Abbvie, Novartis, Jansen, BI, Kimme Hyrich Speakers bureau: KLH has received speaker honoraria from Abbvie, Grant/research support from: KLH has received grant income from Pfizer and BMS, Florenzo Iannone Speakers bureau: FI has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Consultant of: Stated above, Nevsun Inanc Speakers bureau: NI has received consultant and speaker/honoraria from Abbvie, Lilly, MSD, Novartis, Pfizer, Roche, Amgen, Celltrion,UCB., Consultant of: Stated above, Lianne Kearsley-Fleet: None declared, Eirik kristianslund: None declared, Tore K. Kvien Speakers bureau: TKK has received fees for speaking and/or consulting from several companies among them Pfizer, AbbVie, Lilly and Galapagos/Gilead, Consultant of: Stated above, Burkhard Leeb Speakers bureau: BFL has received speaker honoraria from Sandoz, Abbvie, Eli-Lilly, Pfizer, Roche, Grünenthal, Biogen, Celgene, Galina Lukina Speakers bureau: GVL has received speaker fees from Abbvie, Lilly, Novartis, MSD, Roche, Pfizer, Dan Nordström Consultant of: DCN has acted as consultant for AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Karel Pavelka Speakers bureau: KP has received honoraria for lectures: MSD, Pfizer, Roche, Eli Lilly, Medac, UCB, SOBI, Biogen, Sandoz, Viatris, Manuel Pombo-Suarez Speakers bureau: MPS reports advisor and speaker honoraria from Janssen, Lilly, MSD, Novartis, Sanofi, Consultant of: Stated above, Ziga Rotar Speakers bureau: ZR has received fees for speaking/consulting from several companies among them Pfizer, AbbVie, and Eli Lilly, Consultant of: Stated above, Maria Jose Santos Speakers bureau: MJS has received speaker fees from Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Delphine Courvoisier: None declared, Kim Lauper Speakers bureau: KL reports speakers fees for Pfizer, Viatris and Celltrion, Consultant of: KL reports consulting fees for Pfizer, Axel Finckh Speakers bureau: AF reports honoraria and consultancies from Pfizer, BMS, MSD, Eli-Lilly, AbbVie, Galapagos, Mylan, UCB, Viatris, Consultant of: Stated above, Grant/research support from: AF reports grants from Pfizer INC, AbbVie, Galapagos, Eli Lilly

BackgroundThe long-term retention rate of a biological drug is a surrogate marker of its effectiveness and tolerability.ObjectivesWe assessed the probability of golimumab retention (persistence or drug survival) and the associated factors in a large cohort of patients with rheumatic diseases, with up to 8 years of follow-up.MethodsThis was an analysis of the BIOBADASER database (Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency) on all adult patients who had initiated golimumab for treating rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (SpA). The probability of golimumab retention was assessed with the Kaplan-Meier method, differences between groups with the log-rank test, and factors related to retention with a Cox-regression model. Patients were right-censored if they were still treated with golimumab at the last observation for data analysis.ResultsA total of 885 patients were included, of whom 59 had received golimumab in 2 separate cycles (with a grace period of 3 months), totaling 944 cycles of treatment (286 RA, 396 axial SpA and 262 PsA). At golimumab initiation, mean (SD) age was 52 (13) years, 54% were women and median duration of disease was 7.6 (2.8-14.4) years. Golimumab was prescribed as first, second and third/subsequent biological drug in 313 (33%), 303 (32%) and 328 (35%) treatments. Concomitant medications at golimumab initiation included methotrexate (MTX) (32%), steroids (29%), leflunomide (13%) and sulphasalazine (6%). The probability of retention of golimumab since treatment initiation was 71% (95% confidence interval [CI]: 68 – 74) at year 1, 60% (95% CI: 57-63) at year 2, 54% (95% CI: 51-58) at year 3, 48% (95% CI: 44-51) at year 4, 44% (95% CI: 40-48) at year 5, 41% (95% CI: 37-45) at year 6 and 38% (95% CI: 33-42) at year 7 and at year 8. In bivariate analysis, the retention rate was higher when golimumab was used as first biological agent (p log-rank Table 1.Cox-regression analysis. Hazard Ratio for discontinuation of golimumabHazard Ratio95% Confidence intervalpAge at golimumab initiation1.011.00-1.020.063Gender (women vs men)1.230.98-1.550.079Axial SpA vs RA0.590.44-0.80PsA vs RA0.670.51-0.890.005Second vs first biological drug1.521.17-1.970.002Third or further vs first biological drug1.791.38-2.32Corticosteroids1.461.16-1.850.001Methotrexate0.790.63-0.990.041Disease activity over the median*1.291.05-1.590.015*DAS28 > 4.3 (RA, PsA) or BASDAI > 5.6 (axial SpA) at golimumab initiationFigure 1.ConclusionThis study provides new information on long-term golimumab effectiveness for the treatment or rheumatic diseases, with retention rates of 71% at year 1, 44% at year 5 and 38% at year 8. The probability of golimumab retention was higher as first biological drug, in patients with PsA or axial SpA and in those treated with methotrexate, and lower in those treated with steroids or with higher disease activity at golimumab initiation.AcknowledgementsBIOBADASER is funded by the Spanish Society of Rheumatology, the Spanish Agency of Medicines and by different pharmaceutical companies. The present study was funded by MSD, Spain.have no acknowledgements to declare.Disclosure of InterestsManuel Pombo-Suarez: None declared, Daniel Seoane-Mato: None declared, Luis Cea-Calvo Employee of: Medical Affairs, MSD Spain, Federico Diaz-Gonzalez: None declared, Fernando Sánchez-Alonso: None declared, Marta Sánchez-Jareño Employee of: Medical Affairs, MSD Spain, Francisco Javier Manero Ruiz: None declared, Lucía Ruiz: None declared, Vega Jovani: None declared, Isabel Castrejon: None declared

BackgroundTreatment options for rheumatic diseases have evolved to include mechanisms of action beyond tumor necrosis factor inhibitors (TNFi). While non-TNFi biologics and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDS) have been studied as first-line therapy or after TNFi discontinuation, data on the use of TNFis after discontinuation of these drugs is scarce.ObjectivesWe assessed the probability of retention (persistence or drug survival) of golimumab in patients with rheumatic diseases when used after discontinuation of non-TNFi biologicals or tsDMARDs.MethodsCharacteristics of all adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (SpA) who had initiated golimumab after discontinuation of non-TNFi biologicals or tsDMARDs in the BIOBADASER database were analyzed. The probability of golimumab retention was assessed with the Kaplan-Meier method, and differences between groups with the log-rank test. Patients were right-censored if they were still treated with golimumab at the last observation for data analysis. We also compared the probability of retention of patients who initiated golimumab after discontinuation of non-TNFi biologicals or tsDMARDs with that of patients who initiated it after discontinuation of TNFis.ResultsA total of 125 patients (85 [68%] women) with RA (n=72), axSpA (n=23), or PsA (n=30) had initiated golimumab after discontinuation of non-TNFi biologicals or tsDMARD. Golimumab had been initiated as second line of therapy (i.e., after discontinuation of a first non-TNFi biological or tsDMARD) in 26 patients (21%), as third in 29 (23%) and as fourth/subsequent line of therapy in 70 patients (56%). Upon golimumab initiation, the median disease duration was 10.0 years. The most common previously discontinued therapies were secukinumab (n=34) and abatacept (n=23). The retention rates of golimumab were 61% (95% confidence interval [CI]: 51-69) at year 1 (number at risk: 66), 46% (95% CI: 36-55) at year 2 (number at risk: 39), 40% (95% CI: 30-50) at year 3 (number at risk: 23) and 33% (95% CI: 23-44) at year 4 (number at risk: 13). There were no differences in retention rates over 4 years when golimumab was used as the second, third, or fourth/subsequent line of therapy (p=0.462). Retention rate was lower in RA patients (26% at year 3) than in axial SpA (68%) or PsA (49%) (p=0.002) (Figure 1). As second line therapy, the 3-year retention rate of golimumab was slightly lower when it was initiated after non-TNFi biologicals/tsDMARD than when the previously discontinued therapy was a TNFi (32% vs 55%, p=0.119), but the figures were similar when it was initiated as third (52% after non-TNFi biologicals/tsDMARD vs 50% after TNFi, p=0.838) or as fourth/subsequent line of therapy (37% vs 44% respectively, p=0.554).ConclusionWe present, for the first time, 4-year retention rates for golimumab in patients who discontinued non-TNFi biologicals or tsDMARDs, most of them in third and fourth/subsequent line of therapy. In this difficult-to-treat rheumatic population, overall golimumab retention rates were favorable through 4 years of treatment, with higher rates in SpA and PsA compared to RA patients.Figure 1.AcknowledgementsBIOBADASER is funded by the Spanish Society of Rheumatology, the Spanish Agency of Medicines and by different pharmaceutical companies. This study was funded by MSD, Spain.Disclosure of InterestsManuel Pombo-Suarez: None declared, Daniel Seoane-Mato: None declared, Federico Diaz-Gonzalez: None declared, Fernando Sánchez-Alonso: None declared, Luis Cea-Calvo Employee of: MSD Spain, Marta Sánchez-Jareño Employee of: MSD Spain, Vega Jovani: None declared, Paula Pretel: None declared, Francisco Javier Manero Ruiz: None declared, Isabel Castrejon: None declared