Pharmacological management of connective tissue disease-associated pulmonary arterial hypertension

ABSTRACT

Introduction

Pulmonary arterial hypertension (PAH) is a severe, progressive pulmonary vasculopathy (Group 1 Pulmonary Hypertension (PH)) that complicates the course of many connective tissue diseases (CTD). Detailed testing is required to differentiate PAH from other types of PH caused by CTD such as left heart disease (Group 2 PH), pulmonary parenchymal disease (Group 3 PH), and chronic thromboembolic pulmonary hypertension (Group 4 PH). PAH is most frequently seen in systemic sclerosis but can also be seen with systemic lupus erythematosus, mixed CTD, and primary Sjogren’s syndrome.

Areas covered

This review discusses the epidemiology of CTD-associated PAH, outlines the complex diagnosis approach, and finishes with an in-depth discussion on the current treatment paradigm. Focus is placed on challenges faced in the treatment of CTD-associated PAH, (decreased efficacy and poorer tolerance of pharmacological therapies) and includes a discussion on the future investigational treatments.

Expert opinion

Despite significant advances over the past decades with more aggressive treatment algorithms, CTD-associated PAH patients continue to have poorer survival compared to those with idiopathic PAH. This review highlights factors leading to disparate outcomes compared to other forms of PAH, and discusses on further improvements that may increase quality of life and survival for CTD-associated PAH patients.

KEYWORDS:

• Pulmonary hypertension
• pulmonary arterial hypertension
• connective tissue disease
• systemic sclerosis
• therapy

Article highlights

• Pulmonary hypertension is a frequent complication of various connective tissue diseases, most frequently systemic sclerosis and systemic lupus erythematous

• Intrinsic pulmonary vasculopathy must be distinguished from pulmonary hypertension from other causes which manifest from various tissue involvements from the underlying CTD

• Screening for pulmonary arterial hypertension, particularly in systemic sclerosis patients, has been associated with milder functional and hemodynamic impairment and an improved survival

• Dual upfront PAH therapy has been shown to be safe and is associated with improved transplant-free survival

• The survival rate for patients with CTD-associated PAH has improved in the modern era of therapy but the risk of death remains high compared to the overall PAH population

Declaration of interest

A Boucly has relationships with pharmaceutical companies such as Janssen, MSD, AOP Orphan, and Ferrer. In addition to being an investigator in clinical trials involving these companies, relationships include membership of scientific advisory boards, fees for lectures and consultancy.

L Savale has relationships with pharmaceutical companies such as Janssen and MSD. In addition to being an investigator in clinical trials involving these companies, relationships include research grants, membership of scientific advisory boards, fees for lectures and consultancy.

X Jaïs has relationships with pharmaceutical companies such as Bayer, Janssen, and MSD. In addition to being an investigator in clinical trials involving these companies, relationships include research grants, membership of steering committees and scientific advisory boards, fees for lectures and consultancy.

D Montani has relationships with pharmaceutical companies such as Boehringer, Chiesi, Janssen, MSD, and Ferrer. In addition to being an investigator in clinical trials involving these companies, relationships include research grants, membership of steering committees and scientific advisory boards, fees for lectures and consultancy.

M Humbert has relationships with pharmaceutical companies such as Aerovate, Janssen, MSD, Enzyvant, AOP Orphan, Ferrer, Shou Ti, and United Therapeutics. In addition to being an investigator in clinical trials involving these companies, relationships include research grants, membership of steering committees and scientific advisory boards, fees for lectures and consultancy.

O Sitbon has relationships with pharmaceutical companies such as Janssen, MSD, Gossamer Bio, Enzyvant, AOP Orphan, Ferrer, and United Therapeutics. In addition to being an investigator in clinical trials involving these companies, relationships include research grants, membership of steering committees and scientific advisory boards, fees for lectures and consultancy.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.