FRI0539 SURVIVAL IN PATIENTS WITH CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION (CTD-PAH): A META-ANALYSIS OF OBSERVATIONAL REGISTRIES

Background: Although patients with CTD-PAH comprise approximately one third of the overall PAH population, the literature on survival outcomes in CTD-PAH patients overall and by CTD subtype is limited by small sample sizes. We conducted a meta-analysis of more than 4,000 patients with CTD-PAH enrolled in observational registries. Objectives: To determine survival rates in patients with CTD-PAH overall and by CTD subtypes. Methods: The PubMed and EMBASE databases were searched for English-only articles published between January 1, 2000 and November 25, 2019. Inclusion criteria were multicenter registries of adults with WHO group 1 pulmonary hypertension (PAH); conducted in 2000 or later; and survival data for ≥30 patients with CTD-PAH. Meta-analysis of survival was performed using a random-effects model. Survival was estimated for CTD-PAH overall; for CTD-PAH stratified by registries primarily conducted before and after 2010 to assess the impact of new therapies, as well as combination therapy approaches targeting multiple pathways; and for CTD subtypes (systemic sclerosis [SSc] and systemic lupus erythematosus [SLE]). Results: Nineteen registries met inclusion criteria and reported data on 4,008 patients with CTD-PAH. Of these patients, 1,485 had SSc, 456 had SLE, and CTD subtype was not specified in 2,067. CTD-PAH patients had a mean age of 55 years and 87% were female. Most patients (70%) had functional class III or IV disease and the mean 6-minute walk distance at enrollment was 327 m. Among registries that enrolled patients of all PAH etiologies (N=7,829), survival rates in the CTD-PAH subpopulation (n=2113), were 83%, 73%, and 62% at 1-, 2-, and 3- years, respectively. These survival rates were lower than those reported for the overall PAH population: 88%, 79%, and 72% at 1-, 2-, and 3- years, respectively. Numerically higher survival rates at 1-, 2-, and 3- years were observed in CTD-PAH patients treated in 2010 and later: 85% vs 90%, 74% vs 82%, and 65% vs 73%. Among all CTD-PAH patients, survival rates were lower for patients with SSc compared to those with SLE: 88% vs 92%, 75% vs 90%, 67% vs 87% at 1-, 2-, and 3- years, respectively (Figure). Conclusion: Patients with CTD-PAH have a substantial risk of death, however, CTD-PAH patients treated within the last ten years have numerically higher survival rates than those treated earlier. This may be related to increased screening for PAH, especially in SSc (leading to earlier diagnosis) and/or the availability of new treatment approaches. Consistent with clinical observations, patients with SSc have worse survival rates than those with SLE. Given the high risk of mortality in these patients, early detection and upfront aggressive treatment are warranted. References: Acknowledgments: This analysis was funded by Actelion Pharmaceuticals. Disclosure of Interests: Dinesh Khanna Shareholder of: Eicos, Grant/research support from: NIH NIAID, NIH NIAMS, Consultant of: Acceleron, Actelion, Bayer, BMS, Boehringer-Ingelheim, Corbus, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-Aventis/Genzyme, UCB Pharma, Carol Zhao Shareholder of: Actelion Pharmaceuticals US, Inc., Employee of: Actelion Pharmaceuticals US, Inc., Lorinda Chung Grant/research support from: United Therapeutics, Boehringer Ingelheim, Consultant of: Bristol-Myers Squibb, Boehringer Ingelheim, Mitsubishi Tanabe, Eicos Sciences, Gerry Coghlan Grant/research support from: Johnson & Johnson, Consultant of: Bayer, Johnson & Johnson, GlaxoSmithKline, Speakers bureau: Bayer, Johnson & Johnson, GlaxoSmithKline, Rajan Saggar Grant/research support from: Actelion, Gilead Science, United Therapeutics, Consultant of: Actelion, Gilead Science, United Therapeutics, Speakers bureau: Actelion, Gilead Science, United Therapeutics, Stephen Mathai Consultant of: Actelion, Liquidia, Arena, United Therapeutics, Mehul Shah Shareholder of: Actelion Pharmaceuticals US, Inc, Employee of: Actelion Pharmaceuticals US, Inc, John Hartney Shareholder of: Actelion Pharmaceuticals US, Inc, Employee of: Actelion Pharmaceuticals US, Inc, Vallerie McLaughlin Grant/research support from: Reata Pharmaceutics, SoniVie, United Therapeutics, Bayer, Acceleron, Actelion Pharmaceuticals US, Inc., Consultant of: Actelion Pharmaceuticals US, Inc., Acceleron, Arena Pharmaceuticals, Bayer, Caremark, CiVi Biopharma, United Therapeutics