Background Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc).
Objectives In this longitudinal study we aimed to identify factors associated with an unfavourable outcome in SSc patients with early PAH (SSc-PAH) from the DETECT cohort.
Methods DETECT enrolled patients with SSc fulfilling the 1980 ACR classification criteria, with a minimal disease duration of 3 years since the first non-Raynaud symptom, and with a lung diffusion capacity for CO (DLCO) <60% of the predicted value. A broad range of clinical and laboratory parameters potentially associated with PAH were assessed, and right heart catheterisation (RHC) was performed in all patients at baseline. Patients diagnosed with PAH were followed up for up to 3 years in centers that agreed for the longitudinal part of the DETECT study, collecting data on survival, World Health Organization (WHO) Functional Class (FC), hospitalization, and PAH-specific treatment. Disease progression was defined as the occurrence of any of the following: WHO-FC worsening, PAH therapy with a drug combination, hospitalization, or death. Associations between baseline variables and disease progression were assessed by univariable logistic regression.
Results Of the 145 SSc patients with PH enrolled in DETECT, 87 patients were diagnosed with PAH, of whom 57 participated in the longitudinal study (median follow-up time 12.6 months, interquartile range 10.7–21.7 months). Among these 57 patients, 33/57 (57.9%) had mild PAH, in WHO FC I or II. During follow-up, 25/57 (43.9%) patients had disease progression (4 deaths, 11 hospitalizations for PAH, 14 with worsening in WHO FC, and 8 received PAH-specific combination treatment), with a 1-year survival rate of 93%. The following factors [odds ratio, (95% confidence interval)] were associated with disease progression: male gender [4.1 (1.2–14.1)], high Forced Vital Capacity (FVC) % predicted/ DLCO % predicted ratio [3.6 (1.2–10.7)], and high Borg dyspnoea index [1.7 (1.1–2.6)]. Low DLCO (% predicted) was also significantly associated with progression [area under the curve (95% CI) 0.8 (0.6–0.9)], but the relationship was not linear.
Conclusions More than 40% of early-diagnosed SSc-PAH patients in the DETECT cohort who were followed over time had disease progression during a rather short follow-up time, with male gender, functional capacity, and pulmonary function tests (low DLCO, high FVC%/DLCO % predicted ratio) at PAH diagnosis being associated with progression. This suggests that even mild and early detected PAH should be regarded as a high-risk complication of SSc, and every effort to make an early diagnosis is valuable.
Acknowledgements The authors thank all investigators and patients involved in DETECT.
Disclosure of Interest C. Mihai Grant/research support from: Actelion, Geneva Romfarm, Abbvie, Speakers bureau: Actelion, Geneva-Romfarm, Roche-Genentech, M. Antic: None declared, R. Dobrota Grant/research support from: Pfizer, Actelion, Speakers bureau: Actelion, D. Bondermann Consultant for: Actelion, GSK, MSD, Bayer, Pfizer, AOP Orphan, United Therapeutics, H. Chadha-Boreham Employee of: Actelion, G. Coghlan Consultant for: Actelion, GSK, Bayer, United Therapeutics, Endotronics, Speakers bureau: Actelion, GSK, Bayer, United Therapeutics, C. Denton Consultant for: Actelion, M. Doelberg Employee of: Actelion, E. Grünig Grant/research support from: United Therapeutics, Actelion, MSD/Bayer, GSK, Consultant for: United Therapeutics, Actelion, MSD/Bayer, GSK, Speakers bureau: United Therapeutics, Actelion, MSD/Bayer, GSK, D. Khanna Grant/research support from: Bayer, BMS, Genentech/Roche, Sanofi-Aventis, NIH K24AR063120, Consultant for: Actelion, Bayer, Covis, Cytori, EMD Serono, Genentech/Roche, Gilead, GSK, Sanofi-Aventis, V. McLaughlin Consultant for: Actelion, U. Müller-Ladner Consultant for: Actelion, Speakers bureau: Actelion, J. Pope Consultant for: Actelion, Bayer, BMS, Merck, Roche, D. Rosenberg Employee of: Actelion, J. Seibold Consultant for: Acer, Actelion, Anthera, arGen-X, aTyr, Bayer, Blade, Boehringer-Ingelheim, Bristol Myers Squibb, Biogen Idec, Covis, Eiger, EMD Serono, Genkyotex, Gilead, Ironwood, Medac, MedImmune, Mitsubishi, Octapharma, Roche-Genentech, Sanofi, Teva and United Therapeutics., M. Vonk Consultant for: Actelion, O. Distler Grant/research support from: 4 D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-Genentech, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa, Consultant for: 4 D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemomAb, EpiPharm, Ergonex, espeRare foundation, GSK,Roche-Genentech, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa