POS0799 EFFICACY OF BDMARDS IN EARLY VERSUS ESTABLISHED DISEASE IN AXIAL SPONDYLOARTHRITIS: A META-ANALYSIS OF RANDOMIZED TRIALS
Authors: D. Benavent, V. Navarro-Compán, D. Capelusnik, S. Ramiro
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> A consensus definition of 'early axial spondyloarthritis (axSpA)' for the research setting was recently developed under the auspices of Assessment of SpondyloArthritis international Society (ASAS) [1]. The definition (axial symptoms ≤ 2 years) was expert-based given the scarcity of evidence on treatment outcomes according to the different thresholds of symptom duration [2]. <h3>Objectives:</h3> We conducted a meta-analysis of all placebo-randomised controlled trials (RCTs) of approved bDMARDs and tsDMARDs in patients with axSpA, with the aim of investigating the influence of symptom duration on treatment response. <h3>Methods:</h3> AxSpA RCTs were identified from systematic literature reviews informing the ASAS- European Alliance of Associations for Rheumatology (EULAR) management recommendations [3]. Eligibility criteria were RCTs involving adult axSpA patients treated with b/tsDMARDs compared to placebo, ensuring at least 20% of patients in the early disease group according to at least one specific symptom duration threshold (1, 2, 3, 4 or 5 years), and assessing efficacy by any of the selected primary/secondary outcomes. As these stratified data are mostly not published, access to the individual RCT data was requested. Vivli, ClinicalStudyDataRequest and Engagezone data-sharing platforms were used to analyse the individual studies. Patients were categorized based on symptom duration into early or established disease, stratified in groups according to the referred thresholds, and outcomes were compared between the groups. The primary outcome was ASAS40 response, with secondary outcomes including ASAS20, ASAS 5/6, ASAS partial remission, Axial Spondyloarthritis Disease Activity Score (ASDAS) clinical important improvement, ASDAS major improvement, ASDAS low disease activity and ASDAS-inactive disease, at the timing of the primary endpoint. For each trial, treatment effects of b/tsDMARDs vs PBO were assessed through relative risks (RR) and RR ratios (RRR), according to the defined symptom duration thresholds. A meta-analysis was conducted across all included RCTs, using random effects. <h3>Results:</h3> In total 11 RCTs fulfilled the eligibility criteria and could be included, involving 3,272 patients with axSpA; 7 of these studies were eligible for the analysis of the primary endpoint for having ASAS40 response available. Among the included studies there were four studies with golimumab, two with certolizumab and secukinumab each, and one with adalimumab, etanercept and ixekizumab each- no studies with tsDMARDs were included. Mean (standard deviation) age of patients was 37.9 (11.6) years, mean symptom duration 9.3 (9.2) years and 59% were male. Figure 1 shows the pooled RRR of bDMARDs vs PBO in early vs established disease for different outcomes and according to different symptom duration thresholds. Only 1 study was eligible for the 1-year cut-off and therefore pooled outcomes could not be assessed. With the 2-year threshold, the RR for the ASAS40 at the timing of the primary endpoint (weeks 12-16) with bDMARD vs PBO was not different in patients with early disease (RR 2.04 [1.48–2.84]) as compared with established disease (RR 2.28 [1.65–3.15]). None of the individual studies yielded a significant RRR for ASAS40 for early versus established disease (Figure 2). The pooled ASAS40 RRR for the 2-year threshold was 0.88 [0.62-1.24]). With the 3-year threshold, the RRR for ASAS40 was 1.14 [0.75-1.75]), with 4-years 1.11 [0.80-1.54]) and with 5-years, 1.08 [0.78-1.49]). None of the remaining outcomes yielded a significant RRR for early vs established disease according to different thresholds. <h3>Conclusion:</h3> In this meta-analysis of RCTs, no significant difference has been found in the effect of bDMARDs vs PBO in early compared to established axSpA, defined according to several thresholds of symptom duration (between 2 and 5 years). Treating patients earlier or later in the disease course translates into the achievement of comparable short-term clinical outcomes. <h3>REFERENCES:</h3> [1] Navarro-Compán V et al. Ann Rheum Dis. 2023;ard-2023-224232. [2] Capelusnik D et al. Rheumatology (Oxford).2023;62(4):1398-1409. [3] Webers C et al. Ann Rheum Dis.2023;82(1):130-141. <h3>Acknowledgements:</h3> This abstract is based on research using data from data contributors Eli Lilly, Janssen, Pfizer and UCB that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and Vivli, AbbVie, Eli Lilly, Janssen, Pfizer and UCB are not in any way responsible for, the contents of this publication. Data contributors. This study, carried out under YODA Project #2022-4962, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the YODA Project or JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C. Novartis and MSD have made data available through ClinicalStudyDataRequest and Engagezone platforms, respectively. <h3>Disclosure of Interests:</h3> Diego Benavent UCB, Lilly, Galapagos, BMS, MSD, Novartis, Victoria Navarro-Compán AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer, UCB Pharma; Grants: AbbVie, Novartis, Fresenius Kabi, Dafne Capelusnik: None declared, Sofia Ramiro Research grants and/or consulting fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB, Sanofi.