Systemic Sclerosis-associated Interstitial Lung Disease Research Articles

Current Treatment of Systemic Sclerosis-Associated Interstitial Lung Disease

Systemic sclerosis (SSc) is a connective tissue disease characterized by immune irregularity, vasculopathy and excessive collagen production, which causes skin and internal organ fibrosis. Although SSc often affects multiple organs and/or systems, lung involvement and especially interstitial lung disease (ILD) are the leading cause of death in this disease. The fact that different treatment options have been raised in recent years has given hope to clinicians in the management of this disease. This article will also review the current treatment options of SSc-ILD.

Pirfenidone exacerbates Th2-driven vasculopathy in a mouse model of systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung disease (SSc-ILD) are scarce. We assessed the effects of pirfenidone in a mouse model of SSc-ILD. Pulmonary function, inflammation and collagen deposition in response to pirfenidone were assessed in Fra-2-overexpressing transgenic (Fra-2 TG) and bleomycin-treated mice. In Fra-2 TG mice, lung transcriptome was analysed after pirfenidone treatment. In vitro, pirfenidone effects on human eosinophil and endothelial cell function were analysed using flow cytometry-based assays and electric cell-substrate impedance measurements, respectively. Pirfenidone treatment attenuated pulmonary remodelling in the bleomycin model, but aggravated pulmonary inflammation, fibrosis and vascular remodelling in Fra-2 TG mice. Pirfenidone increased interleukin (IL)-4 levels and eosinophil numbers in lung tissue of Fra-2 TG mice without directly affecting eosinophil activation and migration in vitro. A pronounced immune response with high levels of cytokines/chemokines and disturbed endothelial integrity with low vascular endothelial (VE)-cadherin levels was observed in pirfenidone-treated Fra-2 TG mice. In contrast, eosinophil and VE-cadherin levels were unchanged in bleomycin-treated mice and not influenced by pirfenidone. In vitro, pirfenidone exacerbated the IL-4 induced reduction of endothelial barrier resistance, leading to higher leukocyte transmigration. This study shows that antifibrotic properties of pirfenidone may be overruled by unwanted interactions with pre-injured endothelium in a setting of high T-helper type 2 inflammation in a model of SSc-ILD. Careful ILD patient phenotyping may be required to exploit benefits of pirfenidone while avoiding therapy failure and additional lung damage in some patients.

Incidence Rate and Prevalence of Systemic Sclerosis and Systemic Sclerosis-Associated Interstitial Lung Disease in Japan: Analysis Using Japanese Claims Databases.

IntroductionSystemic sclerosis (SSc) is a complex autoimmune disease with increased mortality, and interstitial lung disease (ILD) is a major cause of death. There are no recent epidemiological data on SSc and SSc-associated ILD (SSc-ILD) in Japan and little is known about how patients with these diseases are treated.MethodsThe incidence rate and prevalence of SSc and SSc-ILD in Japan were estimated using the Japanese Medical Data Centre (JMDC) database. The demographic and clinical characteristics of patients and the immunomodulatory medications they received were also assessed using JMDC and the Medical Data Vision (MDV) databases. All analyses were descriptive.ResultsThe overall incidence rates of SSc and SSc-ILD per 100,000 person-years were 6.6 (95% confidence interval [CI] 6.2–7.1) and 1.9 (95% CI 1.6–2.1), respectively, and the overall prevalence per 100,000 persons was 37.0 (95% CI 35.6–38.5) and 13.9 (95% CI 13.0–14.8), respectively. ILD was the most common comorbidity in patients with SSc present in approximately 30% of patients (JMDC, 29.3%; MDV, 30.1%). The immunomodulatory medications prescribed were similar in patients with SSc and SSc-ILD, and each of the medications in this analysis was prescribed in less than 15% of patients.ConclusionWe have demonstrated that estimates of prevalence and incidence rates of SSc and SSc-ILD in Japan are comparable to similar database studies conducted in the USA, using a medical claims database. Only a small proportion of patients were receiving immunomodulatory treatments, suggesting undertreatment in Japan. Incidence Rate and Prevalence of Systemic Sclerosis and Systemic Sclerosis-associated Interstitial Lung Disease in Japan: Analysis Using Japanese Claims Databases—A Video . (MP4 68892 KB)Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02078-5.

Patient preferences for the treatment of systemic sclerosis-associated interstitial lung disease: a discrete choice experiment.

ObjectivesTreatments for SSc-associated interstitial lung disease (SSc-ILD) differ in attributes, i.e. mode of administration, adverse events (AEs) and efficacy. As physicians and patients may perceive treatments differently, shared decision-making can be essential for optimal treatment provision. We therefore aimed to quantify patient preferences for different treatment attributes.MethodsSeven SSc-ILD attributes were identified from mixed-methods research and clinician input: mode of administration, shortness of breath, skin tightness, cough, tiredness, risk of gastrointestinal AEs (GI-AEs) and risk of serious and non-serious infections. Patients with SSc-ILD completed an online discrete choice experiment (DCE) in which they were asked to repeatedly choose between two alternatives characterized by varying severity levels of the included attributes. The data were analysed using a multinomial logit model; relative attribute importance and maximum acceptable risk measures were calculated.ResultsOverall, 231 patients with SSc-ILD completed the DCE. Patients preferred twice-daily oral treatments and 6–12 monthly infusions. Patients’ choices were mostly influenced by the risk of GI-AEs or infections. Improvement was more important in respiratory symptoms than in skin tightness. Concerning trade-offs, patients accepted different levels of increase in GI-AE risk: +21% if it reduced the infusions’ frequency; +15% if changing to an oral treatment; up to +37% if it improved breathlessness; and up to +36% if it reduced the risk of infections.ConclusionsThis is the first study to quantitatively elicit patients’ preferences for treatment attributes in SSc-ILD. Patients showed willingness to make trade-offs, providing a firm basis for shared decision-making in clinical practice.

Additional points to consider before incorporating the Food and Drug Administration–approved therapies for systemic sclerosis–associated interstitial lung disease: comment on the article by Khanna et al

We congratulate the authors for the excellent review, not only restricted to recently approved therapies, on the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) (1). However, it is our opinion that some aspects that currently affect our medical practice merit further commentary. The pandemic of COVID-19 has generated unique challenges in the therapy of SSc-ILD, especially impacting the decision to start treatment. While there is no evidence suggesting that cyclophosphamide or rituximab can reduce mortality in SSc-ILD (2), these drugs have been associated with higher incidence of serious outcomes and mortality in COVID-19 patients (3, 4).

Nintedanib in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Subgroup Analyses by Autoantibody Status and Modified Rodnan Skin Thickness Score.

ObjectiveUsing data from the SENSCIS trial, these analyses were undertaken to assess the effects of nintedanib versus placebo in subgroups of patients with systemic sclerosis–associated interstitial lung disease (SSc‐ILD), based on characteristics previously identified as being associated with the progression of SSc‐ILD.MethodsPatients with SSc‐ILD were randomized to receive either nintedanib or placebo, stratified by anti–topoisomerase I antibody (ATA) status. We assessed the rate of decline in forced vital capacity (FVC) (expressed in ml/year) over 52 weeks in subgroups based on baseline ATA status, modified Rodnan skin thickness score (MRSS) (<18 versus ≥18), and SSc subtype (limited cutaneous SSc [lcSSc] versus diffuse cutaneous SSc [dcSSc]).ResultsAt baseline, 60.8% of 576 patients who received treatment with either nintedanib or placebo were positive for ATA, 51.9% had dcSSc, and 77.5% of 574 patients with MRSS data available had an MRSS of <18. The effect of nintedanib versus placebo on reducing the rate of decline in FVC (ml/year) was numerically more pronounced in ATA‐negative patients compared to ATA‐positive patients (adjusted difference in the rate of FVC decline, 57.2 ml/year [95% confidence interval (95% CI) –3.5, 118.0] versus 29.9 ml/year [95% CI –19.1, 78.8]), in patients with a baseline MRSS ≥18 compared to those with a baseline MRSS of <18 (adjusted difference in the rate of FVC decline, 88.7 ml/year [95% CI 7.7, 169.8] versus 26.4 ml/year [95% CI –16.8, 69.6]), and in patients with dcSSc compared to those with lcSSc (adjusted difference in the rate of FVC decline, 56.6 ml/year [95% CI 3.2, 110.0] versus 25.3 ml/year [95% CI –28.9, 79.6]). However, all exploratory interaction P values were nonsignificant (all P > 0.05), indicating that there was no heterogeneity in the effect of nintedanib versus placebo between these subgroups of patients.ConclusionIn patients with SSc‐ILD, reduction in the annual rate of decline in FVC among patients receiving nintedanib compared to those receiving placebo was not found to be heterogenous across subgroups based on ATA status, MRSS, or SSc subtype.

Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis

BackgroundInterstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.MethodsWe used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.ResultsThere was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.ConclusionsThe association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.Trial registrationClinicalTrials.govNCT02597933. Registered on 8 October 2015.

Diagnosis and monitoring of systemic sclerosis-associated interstitial lung disease using high-resolution computed tomography.

Patients with systemic sclerosis are at high risk of developing systemic sclerosis–associated interstitial lung disease. Symptoms and outcomes of systemic sclerosis–associated interstitial lung disease range from subclinical lung involvement to respiratory failure and death. Early and accurate diagnosis of systemic sclerosis–associated interstitial lung disease is therefore important to enable appropriate intervention. The most sensitive and specific way to diagnose systemic sclerosis–associated interstitial lung disease is by high-resolution computed tomography, and experts recommend that high-resolution computed tomography should be performed in all patients with systemic sclerosis at the time of initial diagnosis. In addition to being an important screening and diagnostic tool, high-resolution computed tomography can be used to evaluate disease extent in systemic sclerosis–associated interstitial lung disease and may be helpful in assessing prognosis in some patients. Currently, there is no consensus with regards to frequency and scanning intervals in patients at risk of interstitial lung disease development and/or progression. However, expert guidance does suggest that frequency of screening using high-resolution computed tomography should be guided by risk of developing interstitial lung disease. Most experienced clinicians would not repeat high-resolution computed tomography more than once a year or every other year for the first few years unless symptoms arose. Several computed tomography techniques have been developed in recent years that are suitable for regular monitoring, including low-radiation protocols, which, together with other technologies, such as lung ultrasound and magnetic resonance imaging, may further assist in the evaluation and monitoring of patients with systemic sclerosis–associated interstitial lung disease. A video abstract to accompany this article is available at: https://www.globalmedcomms.com/respiratory/Khanna/HRCTinSScILD

Integrative analysis of lung molecular signatures reveals key drivers of systemic sclerosis-associated interstitial lung disease

ObjectivesInterstitial lung disease is a significant comorbidity and the leading cause of mortality in patients with systemic sclerosis. Transcriptomic data of systemic sclerosis-associated interstitial lung disease (SSc-ILD) were analysed to...

Nintedanib bei SSc-ILD

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a rare disease with a progressive nature, eventually leading to lung fibrosis. Nintedanib, a tyrosine kinase inhibitor, is a widely accepted drug for treating idiopathic pulmonary fibrosis (IPF), a disease that shares some similarities with SSc-ILD regarding pathological disease processes. In this review, we aim to discuss the pathogenesis of SSc-ILD and the overall role of nintedanib in the management of SSc-ILD. SSc-ILD involves multiple pathological mediators contributing to various pathways that ultimately cause lung fibrosis. The pathogenesis of SSc-ILD is a complex phenomenon and still needs further study. Nintedanib has demonstrated its efficacy in the treatment of SSc-ILD by reducing the progression of the pathological process. It has also proven its clinical significance in the management of SSc-ILD. However, the currently available literature does not have any evidence to compare the effectiveness of nintedanib with the already available treatment modalities such as cyclophosphamide (CYC), mycophenolate mofetil (MMF), and azathioprine (AZT). The current literature also lacks information about nintedanib&amp;apos;s long-term consequences on patients with SSc-ILD. Therefore, to create better evidence-based treatment guidelines, we recommend that researchers conduct randomized clinical trials comparing nintedanib to MMF, CYC, AZT, etc., and continue surveillance to explore the long-term consequences of nintedanib.

The role of antifibrotic therapies in the treatment of systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is a rare autoimmune condition with complex pathogenesis characterized by a heterogeneous presentation and different disease courses. Fibrosis of multiple organs including the lungs favored by inflammation and vasculopathy is the hallmark of SSc. SSc-associated interstitial lung disease (SSc-ILD) is common and can be associated with poor outcomes, this complication being the leading cause of death in recent series. Because of its huge heterogeneity, SSc-ILD management can be very challenging. Immunosuppressive therapy has long been used to prevent SSc-ILD progression with modest effects in clinical trials. However, thanks to a better understating of SSc pathogenesis, innovative therapies including antifibrotics are increasingly being developed. The achievement of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial has led to the approval by drug agencies of the first antifibrotic drug for SSc-ILD. In parallel, other antifibrotics are being investigated as possible beneficial therapies in SSc-ILD. An important unmet need remains to clarify the positioning of the various strategies, such as the added value of combination of immunosuppressants and antifibrotic therapies in patients at high risk of progression. Indeed, irreversible lung injury or self-perpetuated progression highlights the concept of a window of opportunity in SSc-ILD patients. Herewith, we provide an overview of the most significant clinical trials with antifibrotic drugs developed in recent years for the management of SSc-ILD and a viewpoint about their positioning in treatment algorithms.

Prevalence and Outcomes of Systemic Sclerosis-Associated Interstitial Lung Disease at a Tertiary Level Hospital in KwaZulu Natal, South Africa: A Retrospective Review

Prevalence and Outcomes of Systemic Sclerosis-Associated Interstitial Lung Disease at a Tertiary Level Hospital in KwaZulu Natal, South Africa: A Retrospective Review

Pleuroparenchymal fibroelastosis in systemic sclerosis-associated interstitial lung disease.

To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared. PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

High-Resolution Computed Tomography and Lung Ultrasound in Patients with Systemic Sclerosis: Which One to Choose?

Imaging plays a pivotal role in systemic sclerosis for both diagnosis management of pulmonary complications, and high-resolution computed tomography (HRCT) is the most sensitive technique for the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Indeed, several studies have demonstrated that HRCT helps radiologists and clinicians to make a correct diagnosis on the basis of recognised typical patterns for SSc-ILD. Most SSc patients affected by ILD have a non-specific interstitial pneumonia pattern (NISP) on HRCT scan, whilst a minority of cases fulfil the criteria for usual interstitial pneumonia (UIP). Moreover, several recent studies have demonstrated that lung ultrasound (LUS) is an emergent tool in SSc diagnosis and follow-up, although its role is still to be confirmed. Therefore, this article aims at evaluating the role of LUS in SSc screening, aimed at limiting the use of CT to selected cases.

Increased Red Blood Cell Distribution Width in the First Year after Diagnosis Predicts Worsening of Systemic Sclerosis-Associated Interstitial Lung Disease at 5 Years: A Pilot Study.

The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) varies among individuals. Red blood cell distribution width (RDW) has been reported to be a predictor of idiopathic pulmonary fibrosis. However, there are no studies on the relationship between RDW and SSc-ILD. We conducted a retrospective study of 28 patients who were diagnosed with SSc-ILD on their first visit to our hospital and were followed-up for 5 years. The correlation between the changes in RDW, KL-6, and SP-D (ΔRDW, ΔKL-6, ΔSP-D) and the changes in percent-predicted forced lung volume and % carbon monoxide diffusion (Δ%FVC, Δ%DLco) was investigated. ΔRDW at 1 year after diagnosis was significantly inversely correlated with Δ%FVC at 5 years after diagnosis (r = −0.51, p < 0.001) and Δ%DLco at 5 years after diagnosis (r = −0.47, p < 0.001), whereas ΔKL-6 and ΔSP-D at 1 year were not correlated with Δ%FVC or Δ%DLco at 5 years. In the group of SSc-ILD patients with RDW increase in the first year after diagnosis, %FVC and %DLco were significantly lower than baseline at 3-, 4-, and 5-year assessments. In the group of patients without RDW increase in the first year, %FVC and %DLco did not decrease during the follow-up period. In conclusion, the changes in RDW in the first year after diagnosis may be useful surrogate markers to predict the long-term course of SSc-ILD.

Use of mycophenolate mofetil for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

Limited information is available on patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) receiving mycophenolate mofetil (MMF) in Japan. The dose, treatment duration, and patient characteristics of SSc and SSc-ILD patients receiving MMF were investigated. We used data from a Japanese hospital claims database (2008-2020). Data on 486 SSc patients ≥18 years old receiving MMF were captured; 314 had SSc complicated with ILD. The most common initial daily doses were 1000 mg (SSc, 39.5%; SSc-ILD, 38.1%) and 500 mg (SSc, 36.6%; SSc-ILD, 34.6%). The most common maximum daily doses were 1000 mg (SSc, 33.3%; SSc-ILD, 34.9%), 1500 mg (SSc, 24.4%; SSc-ILD, 23.1%), and 2000 mg (SSc, 23.8%; SSc-ILD, 24.4%). Doses ranged from 250 to 3000 mg/day and were similar for SSc and SSc-ILD patients. Over 27% of patients received treatment for >1 year. There was a gradual decrease in steroid doses during MMF treatment. Our study suggests that the off-label use of MMF for SSc and SSc-ILD has been increasing annually since 2015 in Japan. The doses used in patients with SSc and SSc-ILD were similar to the approved doses of MMF for lupus nephritis in Japan.

Kinetic changes in serum KL-6 levels predict disease progression in patients with systemic sclerosis-associated interstitial lung disease

BackgroundThe clinical course of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable. The Krebs von den Lungen-6 (KL-6) glycoprotein is a promising biomarker for reflecting epithelial injury. However, serum KL-6 and its association with the progression of SSc-ILD have been understudied. MethodsWe reviewed 77 consecutive patients with SSc-ILD seen from 2004 to 2016. A longitudinal study of forced vital capacity (FVC), serum KL-6 levels, and changes in KL-6 levels from baseline (ΔKL-6) was conducted. The progression of ILD was defined as ≥10% relative decline in FVC predicted or 5%–10% decline in FVC predicted along with radiological progression on chest computed tomography. The risk factors for ILD progression were assessed by univariate and multivariate regression. ResultsDuring a 5-year follow-up period, 10 (13%) patients showed rapid progression of ILD within 2 years, 39 (51%) showed overall progression during the 5 years, and 28 (36%) had stable disease. Most patients with progressive ILD showed elevations in serum KL-6 levels over the initial 1-year follow-up period. The best cut-off value for ΔKL-6 that predicted progression of ILD was 193 U/mL (sensitivity 81.6%, specificity 92.9%). Multivariate analysis adjusted by age, sex, smoking status, and immunosuppressant use found that diffuse cutaneous SSc (hazard ratio [HR] 4.51; 95% confidence interval [CI] 1.56–13.04) and ΔKL-6 > 193 U/mL from baseline (HR 7.19; 95% CI 3.30–15.69) were independent predictors for progression of SSc-ILD. ConclusionChanges in the KL-6 level can be useful for predicting disease progression in patients with SSc-ILD.

Healthcare utilization and economic burden in systemic sclerosis: a systematic review.

Systemic sclerosis (SSc) is characterized by vasculopathy, fibrosis of skin and internal organs, and autoimmunity with complications including interstitial lung disease, pulmonary hypertension, and digital ulcers with substantial morbidity and disability. Patients with SSc may require considerable healthcare resources with economic impact. The purpose of this systematic review was to provide a narrative synthesis of the economic impact and healthcare resource utilization associated with SSc. MEDLINE and EMBASE were searched from inception to 20 January 2021. Studies were included if they provided information regarding the total, direct and indirect cost of SSc. The cost of SSc subtypes and associated complications was determined. Risk of bias assessments through the Joanna Briggs Institute cross-sectional and case series checklists, and the Newcastle-Ottawa Cohort and Case-Control study scales were performed. A narrative synthesis of included studies was planned. The number of publications retrieved was 1778, of which 34 were included representing 20 cross-sectional, 11 cohort, and three case-control studies. Studies used various methods of calculating cost including prevalence-based cost-of-illness approach and health resource units cost analysis. Overall SSc total annual cost ranged from USD $14959 to $23268 in USA, CAD $10673 to $18453 in Canada, €4607 to €30797 in Europe, and AUD $7060 to $11607 in Oceania. Annual cost for SSc-associated interstitial lung disease and pulmonary hypertension was USD $31285-55446 and $44454-63320, respectively. Cost-calculation methodology varied greatly between included studies. SSc represents a significant patient and health resource economic burden. SSc-associated complications increase economic burden and are variable depending on geographical location and access.

High-resolution computed tomography of the chest for the screening, re-screening and follow-up of systemic sclerosis-associated interstitial lung disease: a EUSTAR-SCTC survey.

High-resolution computed tomography (HRCT) of the chest is the gold standard to diagnose interstitial lung disease (ILD). A prior survey reported that fewer than 60% of SSc-treating rheumatologists order an HRCT for ILD screening in newly diagnosed SSc patients. Since then, efforts were initiated to increase awareness of HRCT as a screening tool. Aim of the present study was to assess efficacy of these awareness programs. European Scleroderma Trials and Research (EUSTAR) and Scleroderma Clinical Trials Consortium (SCTC) members answered a survey about the use of HRCT at diagnosis, the re-screening of patients with a negative baseline HRCT, and the follow-up of HRCT positive SSc-ILD patients. When HRCT was not routinely requested, additional details were collected. Among 205 physician responders, 95.6% would perform an HRCT at SSc diagnosis: 64.9% as routine screening for ILD (65.4% of SSc referral and 63.6% of non-referral physicians) and 30.7% upon clinical suspicion (95.2% in case of crackles on auscultation). Among non-screening physicians, clinical and ethical concerns were major driving factors for not ordering HRCTs. During follow-up, 79.0% of responders would repeat HRCTs in baseline negative cases: 14.1% as routine screening and 64.9% for diagnostic purposes. Finally, 93.2% of responders would repeat a chest HRCT after SSc-ILD diagnosis: 36.6% as yearly routine and 56.6% according to clinical evaluation. The use of baseline HRCT for the screening of SSc-ILD has slightly increased, but awareness programs should be adapted for further improvement. HRCT use in re-screening and follow-up may benefit from validated algorithms.

Systemic Sclerosis-Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration-Approved Therapies in Clinical Practice.

Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases, and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the US Food and Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-associated ILD (SSc-ILD): nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, 2 generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy for the management of SSc-ILD is still to be determined. The objectives of this review are 2-fold: 1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and 2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical versus clinical ILD) and associated risk of progression (low versus high risk). The pharmacologic and nonpharmacologic options for first- and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD.