Pulmonary hypertension (PH) is a life-threatening complication of systemic sclerosis (SSc), thought to be more commonly found in limited cutaneous (lcSSc) compared to diffuse (dcSSc) subset. Since lcSSc has a better prognosis, it is unclear whether a higher occurrence of PH in lcSSc reflects survival bias.
To compare the cumulative PH incidence in disease subsets, after accounting for death as a competing event, in a large multi-center SSc cohort.
Cumulative incidence of PH was studied in 1431 Canadian Scleroderma Research Group (CSRG) database patients (57% lcSSc; follow-up 3.5±2.9 years, range 1-14) by Fine-Gray analysis, unadjusted and adjusted for sex, age and SSc-related autoantibodies (SAS 9.4). Survival curves, predictors of PH development and survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses (SPSS 25.0). Subgroup analysis was performed for PAH.
157 SSc patients had PH (including 117 PAH), either confirmed by RHC or postmortem. Compared to those without PH, lcSSc-PH patients had longer disease and older age at SSc diagnosis, while dcSSc-PH patients - more severe peripheral vascular and gastrointestinal involvement. The cumulative incidences of PH/PAH were similar in dcSSc and lcSSc after accounting for death in the adjusted competitive risk model (Table 1; Fig.1). 47% of PH- and 42% of PAH-patients died over a FU period. Male gender (p<0.0001) and anti-Scl-70 (p<0.001) were associated with earlier PH development, while older age (p=0.006) - with PAH (Table 2). ACA-negativity and older age predicted worse PH prognosis.
Cumulative incidence curves for PH (A) and PAH (B).
Cumulative incidence of PH, after accounting for death as competing event, was comparable in SSc subsets. Vigilance should be considered in males, Scl-70 positive and late age-onset SSc.
Sub-distribution Hazard ratio of incident PH and PAH.
PH PAH Hazard ratio (95% CIs) P values Hazard ratio (95% CIs) P values Crude Model DcSSc vs lcSSc 2.03 (1.13, 3.66) 0.0186 1.60 (0.82, 3.16) 0.1710 Adjusted model DcSSc vs lcSSc 1.82 (0.93, 3.57) 0.0818 1.57 (0.69, 3.59) 0.2812 Female vs male 0.98 (0.42, 2.32) 0.9660 2.10 (0.51, 8.65) 0.3040 Age 1.00 (0.99, 1.02) 0.7041 1.01 (0.98, 1.03) 0.5498 Antibodies ACA vs negative 0.95 (0.46, 1.96) 0.8991 1.08 (0.50, 2.35) 0.8391 ATA vs negative 1.93 (0.84, 4.42) 0.1198 0.59 (0.13, 2.73) 0.4970 Anti-RNAP vs negative 1.24 (0.45, 3.43) 0.6841 1.77 (0.58, 5.44) 0.3181 Disclosure of Interests:
Tatiana Nevskaya: None declared, Yuxuan Jiang: None declared, Mianbo Wang: None declared, Murray Baron: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB