Though mortality rates among patients with connective tissue disease (CTD) complicated by pulmonary arterial hypertension (PAH) remain high, combination therapy with endothelin receptor antagonists (ERA) and phosphodiesterase type-5 (PDE5) inhibitors may improve survival among those with systemic sclerosis (SSc)-PAH, according to study results published in Rheumatology.
Investigators assessed how current treatment regimens affect survival among patients with CTD-PAH.
Data were sourced from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA; ClinicalTrials.gov Identifier: NCT01347216), a European pulmonary hypertension registry.
The investigators assessed all-cause mortality among patients newly diagnosed with PAH based on CTD type, including: SSc-PAH, systemic lupus erythematosus (SLE-PAH), mixed CTD (MCTD-PAH), undifferentiated CTD (UCTD-PAH), and other autoimmune rheumatic diseases.
Survival was further assessed among patients with SSc-PAH according to initial therapy type: ERA, PDE5 inhibitors, or a combination of drugs from each of these 2 classes.
A total of 607 patients were included in the analysis; 390 patients had SSc-PAH, 60 had UCTD-PAH, 34 had SLE-PAH, 33 had MCTD-PAH, and the remaining 90 patients had other autoimmune rheumatic diseases.
Multivariable adjustment of the results indicated that the survival of patients with SSc-PAH was worse than that of patients with other CTD types (P =.001). However, the survival of patients with SSc-PAH improved considerably when they received initial treatment with ERA and PDE5 inhibitor combination therapy vs an ERA (P =.016) or a PDE5 inhibitor (P =.012) alone.
Survival estimates among patients with SSc-PAH at 1, 3, and 5 years were 85%, 59%, and 42%.
In contrast, survival at 1, 3,and 5 years was highest among patients with SLE-PAH (97%, 77%, and 61%), followed by those with MCTD-PAH (97%, 70%, and 59%), those with other autoimmune rheumatic diseases with PAH (92%, 69%, and 55%), and those with UCTD-PAH (88%, 67%, and 52%), respectively.
Study limitations included potential selection bias in favor of patients with more severe disease, small sample sizes among subgroups, and use of a screening algorithm to filter patients with PAH that may have introduced referral bias.
“This survival benefit is noteworthy as the cohorts of patients receiving monotherapy or combination were very similar at baseline. Nevertheless, these findings should be interpreted with caution as the data are observational, and no randomization was involved,” the investigators concluded.
Disclosure: One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies, and COMPERA was supported by Acceleron, Bayer, GSK, Janssen, and OMT. Please see the original reference for a full list of disclosures.
Distler O, Ofner C, Huscher D, et al. Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis. Rheumatol. Published online July 18, 2023. doi: 10.1093/rheumatology/kead360