Future treatment paradigms in pulmonary arterial hypertension: a personal view from physicians, health authorities, and patients

Abstract

Novel treatments in pulmonary arterial hypertension (PAH) with significant pathophysiological and clinical responses have generated renewed interest in changing the course of the disease and achieving long-term disease control. Historically, the term disease modification was coined in rheumatological conditions with therapies that managed to treat the underlying condition as opposed to just alleviating symptoms. With the advent of novel therapies, the term disease modification was introduced in our discussions. Last year, a group of experts discussed this concept in PAH and proposed clinical trial designs to show disease modification in PAH. Taking a step further we convened a group of international experts at the 20th Global CardioVascular Clinical Trialists Forum, patients' representatives, and members of global regulatory agencies to discuss future treatment objectives and trial designs in PAH. The deliberations revealed the difficulty with securely defining disease modification, in that there are no pathophysiological biomarkers that reflect disease activity and studies are not designed or performed in a way that would support such designation. Regulatory agencies indicated they are going away from making this designation a priority in PAH. They declared interest in encouraging trials that advance interventions with significant pathophysiological effect, in particular showing reverse pulmonary vascular remodelling, which is likely to bring about more potent clinical response, partial or complete remission, and perhaps cure. In this Personal View, we provide a review of our understanding of defining disease modification in PAH along with providing definitions of what might constitute a partial or full remission in PAH.