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.

Imaging Features of Autoimmune Disease-Related Interstitial Lung Diseases

“…MDT discussion of imaging findings may result in changes being made to a patient's treatment regimen. For example, the identification of a UIP pattern on HRCT, or evidence of progression of pulmonary fibrosis, may lead clinicians to take a more aggressive approach to pharmacological treatment 9,13,52,[66][67][68] or to refer a patient for the evaluation for lung transplant 69 or autologous stem cell transplant. Changes to how patients are counselled about their prognosis and about palliative care options that may help to preserve their quality of life should also be considered if there is evidence of progressive fibrosis.…”

“…50,51 Expert panels on the monitoring and management of SSc-ILD have also agreed that an increase in the extent of ILD on HRCT indicates progression. 9,13 The criteria for progressive pulmonary fibrosis published by international pulmonology societies in May 2022 included the evidence of radiologic progression, which could include an increased extent or severity of traction bronchiectasis and bronchiolectasis; new ground glass opacity with traction bronchiectasis; new fine reticulation; and/or new or increased honeycombing. 52 However, it is important to be aware that these criteria have not been validated and that visual assessment of HRCT scans does not enable radiologists to predict the progression of ILD nor to assess the worsening of ILD with any degree of accuracy.…”

“…Patients with autoimmune diseases who are at high risk of ILD, including all those diagnosed with SSc and patients with other autoimmune diseases who have risk factors, should be screened for ILD using high-resolution computed tomography (HRCT) 9–13 . Patients with unexplained respiratory symptoms should also undergo HRCT.…”

Anti-U11/U12 Antibodies as a Rare but Important Biomarker in Patients with Systemic Sclerosis: A Narrative Review

“…anti-U11/U12 antibodies are more prevalent in CTP negative patients [ 39 ]. However, this is not only limited to nintedanib, but applies to other novel and alternative treatment approaches in SSc-ILD, including agents with strong-supporting evidence, such as tocilizumab and rituximab [ 55 , 56 ], or others with biological or promising compoundssuch as abatacept, lenabasum, romilkimab, belimumab, bermekimab, brodalumab, tofacitinib, or even rituximab [reviewed in [ 1 , 57 ]].…”

New developments related to lung complications in pediatric rheumatic disease

“…As pulmonary disease can develop over time in patients with SSc, a group of adult pulmonologists and rheumatologists recently published a consensus statement of the management of SSc-associated ILD, which included screening recommendations [12 ▪▪ ]. In addition to performing a physical examination, the group recommended annual screening for ILD by PFTs, both spirometry and DLCO, and by HRCT in addition to autoantibody testing.…”