Expert consensus on the management of systemic sclerosis-associated interstitial lung disease

Abstract

Background: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35-52% of patients and accounting for 20-40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD.

Methods: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from - 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤ - 2.5 or ≥ + 2.5 with a standard deviation not crossing zero.

Results: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants.

Conclusions: This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

Keywords: Algorithms; Autoimmune diseases; Connective tissue diseases; Drug therapy; Pulmonary fibrosis.

Fig. 1

The Delphi process employed for both the first and second Delphi analyses. SSc-ILD systemic sclerosis-associated interstitial lung disease

Fig. 2

Consensus recommendations for screening criteria for SSc-ILD. *Data from the 2022 supplementary Delphi. dcSSc diffuse cutaneous systemic sclerosis, DL_CO diffusing capacity of the lungs for carbon monoxide, HRCT high-resolution computed tomography, ILD interstitial lung disease, PFT pulmonary function test, SD standard deviation, SSc systemic sclerosis

Fig. 3

Consensus recommendations for SSc-ILD treatment criteria. dcSSc diffuse cutaneous SSc, DL_CO diffusing capacity of the lungs for carbon monoxide, FVC forced vital capacity, HRCT high-resolution computed tomography, ILD interstitial lung disease, LLN lower limit of normal, PFT pulmonary function test, RNP ribonucleoprotein, SD standard deviation, SpO₂ peripheral capillary oxygen saturation, SSc systemic sclerosis, Topo topoisomerase

Fig. 4

Consensus recommendations for SSc-ILD treatment paradigm. A Treatment dosage and next steps following treatment response. B Use of nintedanib and tocilizumab. *Data from the 2022 supplementary Delphi. ^†Consensus was not reached in main Delphi analysis. CYC cyclophosphamide, HRCT high-resolution computed tomography, ILD interstitial lung disease, MMF mycophenolate mofetil, PFT pulmonary function test, SD standard deviation, SSc systemic sclerosis, TCZ tocilizumab

Fig. 4

Consensus recommendations for SSc-ILD treatment paradigm. A Treatment dosage and next steps following treatment response. B Use of nintedanib and tocilizumab. *Data from the 2022 supplementary Delphi. ^†Consensus was not reached in main Delphi analysis. CYC cyclophosphamide, HRCT high-resolution computed tomography, ILD interstitial lung disease, MMF mycophenolate mofetil, PFT pulmonary function test, SD standard deviation, SSc systemic sclerosis, TCZ tocilizumab

Fig. 5

Consensus recommendations for duration of SSc-ILD treatment. MMF mycophenolate mofetil, PFT pulmonary function test, SD standard deviation, SSc-ILD systemic sclerosis-associated interstitial lung disease

Fig. 6

Consensus recommendations for monitoring progression and defining treatment success in SSc-ILD. 6MWD 6-min walk distance; CPET cardiopulmonary exercise testing, DL_CO diffusing capacity of the lungs for carbon monoxide, FVC forced vital capacity, HRCT high-resolution computed tomography, ILD interstitial lung disease, NYHA FC New York Heart Association Functional Classification, PFT pulmonary function test, SD standard deviation, SSc-ILD systemic sclerosis-associated ILD

Fig. 7

Summary of the consensus recommendations for the management of patients with SSc-ILD. 6MWD 6-min walk distance, CYC cyclophosphamide, DL_CO diffusing capacity of the lungs for carbon monoxide, FVC forced vital capacity, HRCT high-resolution computed tomography, ILD interstitial lung disease, MMF mycophenolate mofetil, PFT pulmonary function test, PH pulmonary hypertension, SpO₂ peripheral capillary oxygen saturation, SSc-ILD systemic sclerosis-associated ILD, TCZ tocilizumab