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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 BASDAI<40 mm was additionally evaluated. For the setting with one missing component, differences arising between missing one of components 1-4 versus 5-6 were explored. Finally, the performance of imputations in relation to the values of the original score was investigated.ResultsA 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 BASDAI<40 (Table 1). However, separate analyses of components 1-4 and 5-6 as a function of the BASDAI score suggested that imputing any one of the first four BASDAI components resulted in a level of agreement <90% for specific BASDAI values while imputing one of the stiffness components 5-6 always reached a level of agreement >90% (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 BASDAI<40 was less than 95% for values around the cutoff (Figure 1, lower panels).Table 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAI<40 mmLevel of agreement with Dif≤6.9 mm* (%)Correct classification for BASDAI<40 mm** (%)1 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 BASDAI<40 mm as a function of the original scoreConclusionBASDAI 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