PAH treatments less effective in CTD-associated disease

By Shreeya Nanda, Senior medwireNews Reporter

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) have a poorer response to advanced PAH treatments than those with idiopathic disease, finds a meta-analysis.

Therapies were less effective both in terms of improving the 6-minute walk distance (6MWD) and reducing the incidence of clinical worsening, which included hospitalisation or initiation of rescue therapy for PAH, lung transplantation or death, report the researchers from the University of Pennsylvania in Philadelphia, USA.

“While it is premature to use these results in guiding clinical care, clinicians should recognize the differential benefits of therapies and consider the prognosis for patients with various forms of PAH”, they write in the American Journal of Respiratory and Critical Care Medicine.

This meta-analysis included individual patient data from 11 randomised phase III placebo-controlled trials of eight PAH drugs submitted to the US Food and Drug Administration for approval regardless of whether the drugs were ultimately approved.

Among 827 patients with CTD-PAH, of whom more than half had systemic sclerosis, the average placebo-corrected increase in 6MWD at 12 weeks in participants receiving active treatment was 23.1 m. This was significantly less than the mean 40.4 m placebo-corrected improvement observed among 1935 idiopathic PAH patients.

And active treatment compared with placebo did not reduce the risk of clinical worsening in CTD-PAH patients (odds ratio [OR]=0.72), whereas those with idiopathic PAH benefited from treatment (OR=0.34), with significant between-group differences in treatment effect.

Nevertheless, CTD-PAH and idiopathic PAH patients were comparable with respect to the effect of treatment on mortality, with no significant treatment effect on mortality in the overall cohort.

Rennie Rhee and co-investigators point out that the “6MWD has not been validated as a surrogate outcome in PAH and exercise capacity in CTD-PAH is affected by extra-pulmonary comorbidities related to the underlying CTD including arthritis, limited mobility, and deconditioning.”

But they add that clinical worsening is a “clearly relevant endpoint” and that their findings support the existence of heterogeneity in treatment effects in PAH and the corresponding need for identifying more effective therapies for CTD-PAH patients.

The team concludes: “The implementation of classification criteria for the individual CTDs as well as use of rigorous screening measures to exclude other causes of pulmonary hypertension may be needed to elucidate differences in treatment response in CTD-PAH.”

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