Scleroderma Lung Study Research Articles

Interstitial lung disease in rheumatic diseases - newtherapeuticapproaches

Pulmonary involvement is an important aspect in the management of rheumatic diseases. Connective tissue disease-associated interstitial lung diseases (CTD-ILD) are of particular importance, as their occurrence is often decisive for patient outcome. We use corticosteroids, immunosuppressants and eventually also biologicals in the therapy of CTD-ILD.Except for the "Scleroderma Lung Study" (SLS) I and II, which confirm the effectiveness of the immunosuppressive drugs cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in pulmonary involvement of scleroderma (SSc-ILD), there is little data on the treatment of other CTD-ILD. Within the group of biologicals the use of Rituximab (RTX) increases in importance. The currently expected study results compare the efficacy of immunosuppressive drugs (in particular MMF and CYC) with RTX. Other investigated biologicals include Tocilizumab in SSc-ILD and Abatacept in pulmonary involvement in rheumatoid arthritis (RA-ILD). Autologous stem cell transplantation is a potent but potentially risky therapy for severe scleroderma.For the group of pulmonary interstitial diseases of different dignity, including CTD-ILD, with a increasingly fibrosing course despite adequate therapy, (e. g. chronic hypersensitivity pneumonitis, sarcoidosis) the term and concept of "fibrosing interstitial lung diseases with progressive phenotype" (PF-ILD) is being established. In the last months studies were published, which show a positive effect of antifibrotic drugs (Nintedanib, Pirfenidon) in such constellations. Currently a number of other studies regarding the effectiveness of antifibrotics in CTD-ILD are expected to be published. The studies in this field bring new aspects in the understanding of interstitial diseases and have the potential of expanding treatment options in CTD-ILD.The topic of CTD-ILD is a difficult, but at the same time exciting field.

Cyclophosphamide for Systemic Sclerosis-related Interstitial Lung Disease: A Comparison of Scleroderma Lung Study I and II.

To compare safety and efficacy outcomes between the cyclophosphamide (CYC) arms of Scleroderma Lung Study (SLS) I and II. Participants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 mos) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity. SLS I and II CYC participants had similar baseline characteristics. After adjusting for baseline disease severity, there was no difference in the course of the FVC%-predicted (p = 0.535) nor the DLCO%-predicted (p = 0.172) between the SLS I and II CYC arms. In both groups, treatment with CYC led to a significant improvement in the FVC%-predicted from 3 to 12 months, but no significant improvement beyond this point. Treatment with CYC had no effect on the DLCO for either group. Treatment with 1 year of oral CYC led to similar improvements in lung function in both SLS I and II, although the effects were not sustained following cessation of CYC. These results suggest that increasing the duration of ILD therapy may improve outcomes for patients with systemic sclerosis-ILD.

Minimal Clinically Important Differences for the Modified Rodnan Skin Score: Results from the Scleroderma Lung Studies (SLS-I and SLS-II)

ObjectiveThis study aimed to assess the minimal clinically important differences (MCIDs) for the modified Rodnan skin score (mRSS) using combined data from the Scleroderma Lung Studies (I and II).MethodsMCID estimates for the mRSS at 12 months were calculated using three anchors: change in scores on the Health Assessment Questionnaire- Disability Index from baseline to 12 months, change in scores on the Patient Global Assessment from baseline to 12 months, and answer at 12 month for the Short Form-36 health transition question “Compared to one year ago, how would you rate your health in general now?” We determined the mRSS MCID estimates for all participants and for those with diffuse cutaneous systemic sclerosis (dcSSc). We then assessed associations between MCID estimates of mRSS improvement and patient-reported outcomes, using Student’s t test to compare the mean differences in patient outcomes between those who met the MCID improvement criteria versus those who did not meet the improvement criteria.ResultsThe mean (SD) mRSS at baseline was 14.75 (10.72) for all participants and 20.93 (9.61) for those with dcSSc. The MCID estimate for mRSS improvement at 12 months ranged from 3 to 4 units for the overall group (improvement of 20–27% from baseline) and was 5 units for those with dcSSc (improvement of 24% from baseline). Those who met the mRSS MCID improvement criteria had statistically significant improvements in scores on the Short Form-36 Physical Component Summary, the Transition Dyspnea Index, and joint contractures at 12 months.ConclusionMCID estimates for the mRSS were 3–4 units for all participants and 5 units for those with dcSSc. These findings are consistent with previously reported MCID estimates for systemic sclerosis.

Determining progression of scleroderma-related interstitial lung disease.

Interstitial lung disease occurs in the majority of patients with systemic sclerosis. Although interstitial lung disease is the number one cause of death in systemic sclerosis, interstitial lung disease progression rates vary considerably among patients with systemic sclerosis. Some patients with systemic sclerosis-associated interstitial lung disease have sub-clinical disease and may not derive benefit from immunosuppression, while others have a more aggressive interstitial lung disease phenotype. Reliable predictors of interstitial lung disease progression are lacking. The present review describes our current approach to monitoring systemic sclerosis-associated interstitial lung disease progression in clinical practice. To illustrate the marked heterogeneity that exists in interstitial lung disease progression rates in systemic sclerosis, this review presents the individual disease course of five unique patients with systemic sclerosis-associated interstitial lung disease who participated in the Scleroderma Lung Study II. These cases illustrate that treatment response rates vary in systemic sclerosis-associated interstitial lung disease and more research is needed to determine how to predict treatment response in systemic sclerosis-associated interstitial lung disease and to develop personalized treatment approaches for patients with this devastating disease.

Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts

ObjectiveTo assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomised 158...

Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II.

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval. Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe). At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26). Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

Reliability and minimal clinically important differences of forced vital capacity: Results from the Scleroderma Lung Studies (SLS-I and SLS-II).

To assess the reliability and the minimal clinically important differences (MCID) for FVC% predicted in the Scleroderma Lung Study I and II. Using data from SLS I and II (N=300), we evaluated the test-retest reliability for FVC% predicted (FVC%; screening vs. baseline) using intra-class correlation (ICC). MCID estimates at 12 months were calculated in the pooled cohort (SLS-I and II) using 2 anchors: Transition Dyspnea Index (≥change of 1.5 units for improvement and worsening, respectively) and the SF-36 Health Transition question: "Compared to one year ago, how would you rate your health in general now?", where "somewhat better" or "somewhat worse" were defined as the MCID estimates. We next assessed the association of MCID estimates for improvement and worsening of FVC% with patient reported outcomes (PROs) and computer-assisted quantitation of extent of fibrosis (QLF) and of total ILD (QILD) on HRCT. Reliability of FVC%, assessed at a mean of 34 days, was 0.93 for the pooled cohort. The MCID estimates for the pooled cohort at 12 months for FVC% improvement ranged from 3.0 % to 5.3% and for worsening from -3.0% to -3.3%. FVC% improvement by ≥MCID was associated with either statistically significant or numerical improvements in some PROs, QILD, and QLF, while FVC% worsening ≥MCID was associated with statistically significant or numerical worsening of PROs, QILD, and QLF. FVC% has acceptable test-retest reliability, and we have provided the MCID estimates for FVC% in SSc-ILD based changes at 12 months from baseline in two clinical trials. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT00004563 and NCT00883129.

Managing Systemic Sclerosis-Related Interstitial Lung Disease in the Modern Treatment Era

Interstitial lung disease (ILD) affects the majority of patients with systemic sclerosis (SSc) and is the leading cause of death in SSc. Traditionally, treatments for SSc-ILD have targeted broad suppression of the immune system with agents such as cyclophosphamide and mycophenolate. The recently published Scleroderma Lung Study (SLS) II demonstrated that treatment with either oral cyclophosphamide or mycophenolate led to similar improvement in lung function, dyspnea and radiographic extent of fibrosis. However, with the emergence of anti-fibrotic therapy for the treatment of idiopathic pulmonary fibrosis, the repurposing of biologic agents used to treat other connective tissue diseases, and the introduction of hematopoetic stem-cell transplantation for patients with early diffuse SSc, options for managing SSc-ILD have increased. For the first time ever, patients and physicians have choices for how to treat SSc-ILD. At the same time, the study and administration of these novel therapeutic agents have raised important clinical research questions that warrant further investigation. This review describes the current and experimental therapies available for SSc-ILD. This review also explores unanswered questions directly relevant to patient care and future research efforts in this area, including questions on indications for initiation of SSc-ILD therapy, the use of maintenance SSc-ILD therapy and the duration of SSc-ILD therapy. Conducting studies designed to answer these important questions is central to advancing SSc-ILD research and improving outcomes for patients with this devastating disease.

Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II

Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied. We investigated frequent cough (FC) in patients with SSc-ILD (N= 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial. Study participants who reported FC at baseline (61.3%) reported significantly more dyspnea, exhibited more extensive ILD on high-resolution CT, had a lower diffusing capacity for carbon monoxide, and reported more GERD symptoms than did those without FC. Cough-specific QoL was modestly impaired in patients with FC (total LCQ score, 15.4 ± 3.7; normal range, 3-21 [higher scores indicate worse QoL]). The proportion of patients with FC at baseline declined by 44%and 41%over 2 years in the CYC and MMF treatment arms, respectively, and this decline was significantly related to changes in GERD and ILD severity. FC occurs commonly in SSc-ILD, correlates with both the presence and severity of GERD and ILD at baseline, and declines in parallel with improvements in both ILD and GERD over a 2-year course of therapy. Frequent cough might serve as a useful surrogate marker of treatment response in SSc-ILD trials. ClinicalTrials.gov; No.: NCT00883129; URL: www.clinicaltrials.gov.

Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease.

BackgroundIncreased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD.MethodsA total of 142 SSc-ILD patients from Scleroderma Lung Study (SLS) II were randomized in a double-blind, parallel-arm trial, to receive mycophenolate (MMF) for 2 years or oral cyclophosphamide (CYC) for 1 year followed by 1 year of placebo. Plasma CXCL4 levels were measured at baseline, 12 months, and 24 months in SLS II participants (N = 136) and at a single time point in healthy controls (N = 67). A mixed-effects model evaluated the relationship between change in CXCL4 levels and SSc-ILD progression. The primary outcome was the course of the forced vital capacity.ResultsBaseline CXCL4 levels were significantly higher in SSc-ILD patients compared with healthy controls (2699 ± 1489 ng/ml vs 2233 ± 1351 ng/ml (mean ± SD); P = 0.019). However, no significant correlations were identified between CXCL4 levels and extent of ILD at baseline, as measured by the forced vital capacity, diffusing capacity of carbon monoxide, or radiographic extent of ILD. Plasma CXCL4 decreased significantly from baseline to 12 months in all patients (CYC: P < 0.001; MMF: P = 0.006) with no between-treatment differences (CYC vs MMF). Patients with the largest decline in CXCL4 levels during the first 12 months had an improved course of forced vital capacity %-predicted from 12 to 24 months (P = 0.040), even after adjusting for baseline disease severity and treatment arm assignment.ConclusionsLevels of CXCL4 were higher in patients with SSc-ILD compared with controls and decreased in all patients treated with immunosuppressive therapy. While CXCL4 levels were not correlated with extent of ILD at baseline, changes in CXCL4 at 12 months predicted future progression of SSc-ILD from 12 to 24 months. These findings suggest that intermediate-term changes in CXCL4 may have predictive significance for long-term progression of SSc-ILD in patients receiving immunosuppressive therapy.Trial registrationClinicalTrials.gov NCT00883129. Registered 16 April 2009.

Treatment of Systemic Sclerosis-related Interstitial Lung Disease: A Review of Existing and Emerging Therapies.

Although interstitial lung disease accounts for the majority of deaths of patients with systemic sclerosis, treatment options for this manifestation of the disease are limited. Few high-quality, randomized, controlled trials exist for systemic sclerosis-related interstitial lung disease, and historically, studies have favored the use of cyclophosphamide. However, the benefit of cyclophosphamide for this disease is tempered by its complex adverse event profile. More recent studies have demonstrated the effectiveness of mycophenolate for systemic sclerosis-related interstitial lung disease, including Scleroderma Lung Study II. This review highlights the findings of this study, which was the first randomized controlled trial to compare cyclophosphamide with mycophenolate for the treatment of systemic sclerosis-related interstitial lung disease. The results reported in this trial suggest that there is no difference in treatment efficacy between mycophenolate and cyclophosphamide; however, mycophenolate appears to be safer and more tolerable than cyclophosphamide. In light of the ongoing advances in our understanding of the pathogenic mechanisms underlying interstitial lung disease in systemic sclerosis, this review also summarizes novel treatment approaches, presenting clinical and preclinical evidence for rituximab, tocilizumab, pirfenidone, and nintedanib, as well as hematopoietic stem cell transplantation and lung transplantation. This review further explores how reaching a consensus on appropriate study end points, as well as trial enrichment criteria, is central to improving our ability to judiciously evaluate the safety and efficacy of emerging experimental therapies for systemic sclerosis-related interstitial lung disease.

Frequent Cough in Scleroderma-Related Interstitial Lung Disesae (SSc-ILD): Characterisitcs and Response to Potentially Disease-Modifying Therapy in a Randomized Controlled Trial (RCT) (Scleroderma Lung Study II)

Frequent Cough in Scleroderma-Related Interstitial Lung Disesae (SSc-ILD): Characterisitcs and Response to Potentially Disease-Modifying Therapy in a Randomized Controlled Trial (RCT) (Scleroderma Lung Study II)

P014 Quantitative CT as an Outcome Measure in the Scleroderma Lung Study II

P014 <break /> Quantitative CT as an Outcome Measure in the Scleroderma Lung Study II

Transitions to different patterns of interstitial lung disease in scleroderma with and without treatment

ObjectivesThe aim is to investigate whether the 12-month quantitative changes in high-resolution CT (HRCT) measures of interstitial lung disease (ILD) are different, and to understand how they change, in patients...

Predictors of lung function decline in scleroderma-related interstitial lung disease based on high-resolution computed tomography: implications for cohort enrichment in systemic sclerosis-associated interstitial lung disease trials.

BackgroundThe extent of lung involvement visualized by high-resolution computed tomography (HRCT) is a predictor of decline in forced vital capacity (FVC) in scleroderma–interstitial lung disease. Our objective was to evaluate the performance of three different HRCT-defined staging systems in the Scleroderma Lung Study I (SLS I) over a 1-year period.MethodsWe assessed two visual semiquantitative scores: the maximum fibrosis score (MaxFib, the fibrosis score in the zone of maximal lung involvement) and visual assessment of total lung involvement (TLI) as proposed by Goh and Wells. In addition, we evaluated the computer-aided diagnosis and calculated the quantitative percentage with fibrosis (QLF) and TLI.ResultsThe mean duration of the disease was 3.2 years, and the mean FVC was 67.7 %. Regardless of the staging system used, a greater degree of fibrosis/TLI on HRCT scans was associated with a greater decline in FVC in the placebo group. Using the MaxFib and QLF, the mean absolute changes in FVC from baseline were 0.1 % and −1.4 %, respectively, in <25 % lung involvement vs. a change of −6.2 % and −6.9 %, respectively, with >25 % involvement (negative score denotes worsening in FVC). Conversely, cyclophosphamide was able to stabilize decline in FVC in subjects with greater degree of involvement detected by HRCT. Using the visual MaxFib and QLF, the mean absolute improvements in FVC were 1.2 and 1.1, respectively, with >25 % involvement.ConclusionsHRCT-defined lung involvement was a predictor of decline in FVC in SLS I. The choice of staging system for cohort enrichment in a clinical trial depends on feasibility.Trial registrationClinicalTrials.gov identifier: NCT00004563 (Scleroderma Lung Study I)ISRCTN15982171. Registered 19 Aug 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0872-2) contains supplementary material, which is available to authorized users.

Efficacy and Safety of Mycophenolate (MMF) Vs Oral Cyclophosphamide (CYC) for Treatment of Scleroderma-Interstitial Lung Disease (Ssc-ILD): Results of Scleroderma Lung Study II

Efficacy and Safety of Mycophenolate (MMF) Vs Oral Cyclophosphamide (CYC) for Treatment of Scleroderma-Interstitial Lung Disease (Ssc-ILD): Results of Scleroderma Lung Study II

Development of a Composite Outcome Measure for Systemic Sclerosis Related Interstitial Lung Disease.

While systemic sclerosis-related interstitial lung disease (SSc-ILD) trials predominantly use forced vital capacity (FVC) as the primary outcome, combining individual outcomes may lead to a more comprehensive measure of treatment response and minimize the risk of type 1 error. The present analysis aimed to develop a composite outcome measure to assess treatment response in SSc-ILD patients. We used data from the Scleroderma Lung Study I (SLS-I) to create the composite outcome measure. SLS I was a multi-institutional, double-blind clinical trial, in which 158 patients with SSc-ILD were randomized to receive either oral cyclophosphamide (CYC) (titrated to 2.0 mg/kg once daily) or matching placebo for one year. To select the variables for inclusion in the composite outcome, we first performed a univariate analysis using all of the outcome variables measured in SLS I. We subsequently combined the variables with significant treatment effects (p<0.05) in a principal component analysis (PCA) to assess the difference between treatment groups. These variables included the FVC% predicted, computer-based score for quantitative lung fibrosis in the zone of maximum fibrosis (QLF-ZM) from thoracic high-resolution computer tomography (HRCT) scans, transitional dyspnea index (TDI), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 12 months. Of the 158 patients, 82 had complete outcome data and were included in this analysis. There were no significant differences in baseline characteristics between the 82 patients included in this analysis and the remaining 76 patients. The regression model with the first principal component for FVC% predicted, QLF-ZM, TDI and HAQ-DI as the composite outcome demonstrated a significant treatment effect favoring cyclophosphamide (Estimate 0.7 [SE 0.2]; p=0.005). Eliminating FVC% predicted from the composite outcome model did not change the overall treatment effect (Estimate 0.8 [SE 0.2]; p=0.004). The CYC treatment effect observed from using the composite outcome of FVC% predicted, QLF-ZM, TDI and HAQ-DI was stronger than the effect observed using FVC% predicted alone. These findings suggest that combining patient-reported outcomes with structural and physiologic outcomes into a single outcome may serve as a more robust measure of treatment response compared with FVC alone in SSc-ILD trials.

Relationship between quantitative radiographic assessments of interstitial lung disease and physiological and clinical features of systemic sclerosis

ObjectivesExtent of systemic sclerosis (SSc)-related interstitial lung disease (ILD) assessed from thoracic high-resolution CT (HRCT) predicts disease course, mortality and treatment response. While quantitative HRCT analyses of extent of lung...

The Ambitious Goal of Validating Prognostic Biomarkers for Systemic Sclerosis-related Interstitial Lung Disease

Interstitial lung disease (ILD) often complicates the course of systemic sclerosis (SSc), mainly in patients with the diffuse subset of disease and with anti-Scl70 antibody positivity1,2. Postmortem examination gives evidence that nearly all patients with SSc develop pulmonary fibrosis, although to a very different extent individually; high-resolution computed tomography (HRCT) shows interstitial lung involvement in about two-thirds of the cases2. Together with pulmonary arterial hypertension, severe pulmonary fibrosis is the leading cause of SSc-related death, as demonstrated by Steen and Medsger among the very large Pittsburgh cohort3. These data were confirmed by a study of the SSc population included in the European League Against Rheumatism Scleroderma Trials and Research group database4. With regard to the course of ILD, some patients develop severe and rapidly progressive interstitial lung involvement during the early phase of the disease, while others may show an indolent course without a relevant influence on pulmonary function or survival1,5. Assessment of lung involvement and close monitoring of lung function are therefore mandatory. During the last decade efforts have been undertaken to identify predictors of rapid deterioration in SSc lung interstitial involvement. The Scleroderma Lung Study (SLS) and the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) assembled the largest cohorts for this purpose6,7. These efforts were intended mainly to drive treatment choice, but also to avoid serial HRCT scans for patient followup to reduce radiation exposure. One of the most important findings was that, similar to idiopathic pulmonary fibrosis8, the decline in forced vital capacity (FVC) and DLCO turned out to mirror the degree of changes observed on HRCT9. An accelerated rate of decline in FVC is associated with poor survival7. Despite these attempts, … Address correspondence to Dr. F. Bonella, Department of Pneumology and Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Tüschener Weg 40, 45239 Essen, Germany. E-mail: francesco.bonella{at}ruhrlandklinik.uk-essen.de

FRI0396 Double-blind comparison of mycophenolate mofetil and oral cyclophosphamide for treatment of scleroderma-related interstitial lung disease (scleroderma lung study [SLS] II): rationale, design, methods, baseline characteristics and patient disposition

BackgroundCyclophosphamide (CYC), is the only therapy that has been shown thus far to be efficacious in scleroderma-related interstitial lung disease (SSc-ILD). However, the utility of CYC is constrained by its...