The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements

Summary

Background

Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods.

Methods

Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement.

Findings

Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment.

Interpretation

Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD.

Funding

An unrestricted grant from Boehringer Ingelheim International.

Introduction

Patients with systemic sclerosis are at high risk of developing interstitial lung disease (ILD). 50% of patients with systemic sclerosis have ILD when first assessed by high-resolution CT (HRCT),¹ although a lesser proportion of patients have a severe reduction in pulmonary function.² Early diagnosis, severity assessment, prediction of progression, and appropriate treatment of systemic sclerosis-associated ILD is necessary to achieve the best possible patient outcomes.³ However, differences in screening approaches, few treatment options, and an absence of consensus guidelines make effective, early intervention difficult in clinical practice.

Treatment recommendations for the management of systemic sclerosis were updated in 2016 by the European League Against Rheumatism/European Scleroderma Trial and Research group,⁴ and treatment algorithms for systemic sclerosis were published in 2018 by the Scleroderma Algorithm Group.⁵ In 2019, a consensus was established on strongly suggested tools for a minimum annual systemic assessment of organ involvement in systemic sclerosis.⁶ Although these recommendations offer important clinical treatment guidance for systemic sclerosis, statements regarding the specific management of systemic sclerosis-associated ILD are limited to recommendations regarding treatment with cyclophosphamide4, 7 or mycophenolate mofetil,⁵ and multidisciplinary consensus is highly in demand to guide the clinical management of this complex patient group.⁸ Ideally, such guidance would include detailed evidence-based statements on screening, diagnosis, treatment, and assessment of disease progression.⁹ With the availability of nintedanib as the first US FDA-approved treatment to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD,¹⁰ and further treatments in advanced clinical testing, there is a rapidly increasing need for clinical management algorithms leading to improved morbidity and mortality outcomes. Although clinical guidance for systemic sclerosis-associated ILD has been published previously in review articles,11, 12 there are, to our knowledge, no existing recommendations using well established consensus methods.

Research in context

Evidence before this study

Patients with systemic sclerosis are at high risk of developing interstitial lung disease (ILD), but guidance is scarce regarding the specific management of systemic sclerosis-associated ILD. Although clinical guidance for systemic sclerosis-associated ILD has been published in review articles previously, to our knowledge there are no existing recommendations using well established consensus methods. We did a systematic search of the literature from Jan 01, 2012, to April 30, 2018, including grey literature (searched between 1992 and 2011), using multiple electronic databases. Guidelines, meta-analyses, randomised controlled trials, and observational studies reporting on risk stratification, screening, diagnosis, treatment, and management outcomes for patients with systemic sclerosis-associated ILD were included.

Added value of this study

This study provides the first evidence-based expert consensus statements for systemic sclerosis-associated ILD management across six key domains—risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation—and an systemic sclerosis-associated ILD management algorithm for use in clinical practice using well established consensus methods.

Implications of all the available evidence

These evidence-based expert consensus statements provide important clinical guidance for the early identification and medical management of systemic sclerosis-associated ILD, and offer a framework for future treatment decision making.

We therefore aimed to establish expert consensus statements for systemic sclerosis-associated ILD in six key domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) and to develop a management algorithm providing a framework for future clinical decision making. To meet these objectives, an initial set of statements on systemic sclerosis-associated ILD was developed based on a comprehensive systematic literature review, and evidence-based expert consensus was achieved using a modified Delphi process that included 27 European pulmonologists, rheumatologists, and internists.