Pharmacological management of systemic sclerosis associated interstitial lung disease

ABSTRACT

Introduction

Interstitial lung disease (ILD) is a major cause of disease-related morbidity and one of the leading causes of mortality in patients with systemic sclerosis (SSc). Many patients will be diagnosed with SSc before the emergence of clinically meaningful ILD. Screening and early recognition of SSc-ILD allows prompt intervention and improved clinical outcomes. In recent years, clinical trial data from large well-designed randomized controlled trials have greatly enhanced our understanding of the natural history of SSc-ILD and risk factors for progressive disease. These advances have led to the emergence of treatment paradigms designed to address the management of both established and subclinical disease.

Areas covered

The present review shall consider the findings of recent trials and implications for modern pharmacological management of SSc-ILD. Where relevant, knowledge gaps shall be highlighted to outline the potential focus of additional research in this field.

Expert opinion

Recent clinical trial data have confirmed beyond doubt the value of immunomodulatory treatment in SSc-ILD, and it is expected this shall translate into improved clinical outcomes in SSc-ILD. We need better methods of cohort enrichment for SSc-ILD clinical trials, and biomarker discovery may establish molecular signatures allowing more personalized approaches to SSc-ILD prevention and management.

KEYWORDS:

• Systemic sclerosis
• interstitial lung disease
• pharmacotherapy
• clinical trials
• anti-fibrotics
• immunomodulatory therapy

Article highlights

• Interstitial lung disease is a common complication of systemic sclerosis causing significant disease-related morbidity and mortality.

• Risk factors for progressive disease include diffuse cutaneous subtype, lower forced vital capacity and gas transfer, advancing age, male sex, and >20% ILD lung involvement.

• High-quality randomized control data exist for the use of cyclophosphamide and mycophenolate mofetil for SSc-ILD.

• The anti-fibrotic drug nintedanib is licensed for use in SSc-ILD, which is progressing despite the standard treatment.

• Breathlessness can be severely debilitating in SSc-ILD and pharmacological options for management should be considered

Declaration of interest

JD Pauling has received personal support from and/or undertaken consultancy work for Janssen, Astra Zeneca, Permeatus Inc, Boehringher-Ingelheim, and Sojournix Pharma.

H Gunarwardena, SL Barratt, and H Adamali have undertaken consultancy work and received speaker fees from Boehringher-Ingelheim.

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.