POS0211 PAH TREATMENT AT TIME OF DIAGNOSIS IS ASSOCIATED WITH IMPROVED SURVIVAL REGARDLESS OF HEMODYNAMIC THRESHOLDS AND RISK STRATIFICATION - A EUSTAR ANALYSIS
Authors: H. J. Bjørkekjær, C. Bruni, C. Brunborg, P. Carreira, P. Airò, C. P. Simeón-Aznar, M. E. Truchetet, A. Giollo, A. Balbir-Gurman, M. Martin, C. P. Denton, A. Gabrielli, H. Fretheim, H. Bitter, Ø. Midtvedt, K. Broch, A. Andreassen, S. Høie, Y. Tanaka, G. Riemekasten, U. Müller-Ladner, M. Matucci-Cerinic, I. Castellví, E. Siegert, E. Hachulla, Ø. Molberg, O. Distler, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> In recent years, an improvement in the survival rate of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) has been recorded, at least partially attributed to the availability of novel treatment strategies[1]. Upfront combination therapy and treatment adapted to risk stratification of PAH have been recommended in SSc-PAH at time of diagnosis[2]. Recent work does, however, show that a substantial proportion of patients are still not treated according to the current treatment recommendations[3]. <h3>Objectives:</h3> We aimed to characterize untreated SSc-PAH patients from the EUSTAR database and compare outcomes across the patient groups who did and did not receive upfront therapy. <h3>Methods:</h3> We assessed patients in the EUSTAR database who fulfilled the criteria for SSc-PAH according to the new hemodynamic definition of PAH (EUSTAR Project Number: CP122). We excluded patients already on PAH-specific treatment or who had severe interstitial lung disease (ILD), defined as an extent of ILD on HRCT &gt;20% or a FVC &lt;70% in the presence of ILD without available quantification. We defined two mutually SSc-PAH patient groups: (1) those who did not receive upfront treatment and (2) the upfront treatment group who received either mono- or combination therapy with endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5i), and/or prostanoids within 3 months from right heart catheterization. Higher and lower mPAP and PVR groups were defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) &gt;3 WU, and mPAP 21-24 mmHg or PVR 2-3 WU, respectively. Risk stratification was assessed by COMPERA 2.0. Transplant-free survival was evaluated using Kaplan-Meier analysis and log-rank test. The impact of no upfront treatment on mortality was assessed using Cox regression adjusted for age, sex, DLCO, hemodynamic- and risk groups, and pre-existing treatment with ERA, PDE5i, or intermittent prostanoids for Raynaud's and digital ulcers (DUs). <h3>Results:</h3> Of the 890 patients who had right heart catheterization, 359 were eligible (Table 1). Over a median observation period of 3.4 (Q1-Q4: 1.4-6.1) years, 146 (41%) of the patients died and 11 (4%) were lung transplanted. The patient group with no upfront treatment had a lower risk profile at the time of SSc-PAH diagnosis, including a lower WHO functional class, a longer 6-min walk distance, and lower NT-proBNP levels (Table 1). Additionally, they had a higher DLCO and better hemodynamics, with more patients in the lower mPAP and PVR group (Table 1). A higher proportion of patients in the no upfront treatment group were on treatment for Raynaud's and DUs, which may have had an impact on the decision to not start upfront treatment (Table 1). While comorbidities and SSc-specific organ manifestations likely influence PAH treatment decisions, we found no differences in the prevalence of diastolic dysfunction and limited ILD between the groups (Table 1). The proportion of upfront treatment increased with higher mPAP and PVR group, treatment-naïve status, and SSc-PAH diagnosis after 2015; the time when upfront combination therapy was first recommended (Figure 1A). Additionally, patients at higher risk by the COMPERA 2.0 tool did more often receive upfront treatment (Figure 1B). While unadjusted survival did not differ between the SSc-PAH patient group who received upfront treatment and the group who did not (Table 1), multivariable Cox regression analysis showed that no upfront treatment was significantly associated with increased mortality compared to upfront treatment, independent of hemodynamic group, risk stratification, and pre-existing therapies (Figures 1C and D). <h3>Conclusion:</h3> Despite a lower risk profile in SSc-PAH patients that were not treated upfront, our findings indicate that no upfront treatment is associated with worse survival. Hence, this study provides data that strengthens the recommendation of upfront treatment for SSc-PAH, regardless of hemodynamics, risk stratification, and pre-existing therapies. <h3>REFERENCES:</h3> [1] Khanna, D., et al., Arthritis Rheumatol, 2021. [2] Humbert, M., et al., Eur Heart J, 2022. [3] Distler, O., et al., Rheumatology, 2023. <h3>Acknowledgements:</h3> The authors thank all EUSTAR collaborators. <h3>Disclosure of Interests:</h3> Hilde Jenssen Bjørkekjær Janssen, Cosimo Bruni Eli-Lilly, Boehringer Ingelheim, Research grants from Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis Foundation for Bio-medical Research. Educational grants from AbbVie and Wellcome Trust. Congress participation support from Boehringer Ingelheim., Cathrine Brunborg: None declared, Patricia Carreira: None declared, Paolo Airò Bristol Myers Squibb, Bohringer Ingelheim, Novartis, Bristol Myers Squibb, Support for attending meetings and/or travel: CSL Behring, Janssen, Roche, Bristol Myers Squibb, Eli Lilly, Carmen P. Simeón-Aznar Janssen, MSD and Boehringer Ingelheim, Boehringer Ingelheim, Marie-Elise Truchetet Abbvie, Boehringer, Pfizer, MSD, Abbvie, Lilly, Alessandro Giollo Participation on a Data Safety Monitoring Board or Advisory Board: Boheringer, Alexandra Balbir-Gurman: None declared, Mickael Martin GlaxoSmithKline France, Boehringer Ingelheim, CSL Behring France, Christopher P Denton Janssen, GlaxoSmithKline, Boehringer Ingelheim, Janssen, GlaxoSmithKline, Bayer, Sanofi-Aventis, Boehringer Ingelheim, Roche, CSL Behring, Corbus, Acceleron, Horizon, Arxx Therapeutics, Lilly, Novartis, Certa, Abbvie, Arxx Therapeutics, Horizon, GlaxoSmithKline, Armando Gabrielli: None declared, Håvard Fretheim Boehringer ingelheim, Bayer, Helle Bitter Boehringer, Øyvind Midtvedt: None declared, Kaspar Broch Amgen, AstraZeneca, Boehringer, Novartis, Novo Nordisk, Pharmacosmos, Pfizer, Pfizer, Pharmacosmos, Boehringer, AstraZeneca, Arne Andreassen Janssen, Janssen, Sverre Høie: None declared, Yoshiya Tanaka Eli Lilly, AstraZeneca, Abbvie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer, Taiho, Mitsubishi-Tanabe, Eisai, Chugai, Taisho, Gabriela Riemekasten: None declared, Ulf Müller-Ladner: None declared, Marco Matucci-Cerinic: None declared, Ivan Castellví: None declared, Elise Siegert: None declared, Eric Hachulla Johnson &amp; Johnson, GSK, Roche-Chugai, Johnson &amp; Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, GSK, Roche-Chugai, Sanofi-Genzyme, Øyvind Molberg: None declared, Oliver Distler Boehringer Ingelheim, Janssen, Medscape, CITUS AG, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur and UCB., Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp &amp; Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp &amp; Dohme and Roche, Boehringer Ingelheim, Janssen.