scholarly journals SAT0569 “IMAGES ARE MORE THAN PICTURES, THEY ARE DATA” [1] – EXPLORATION OF RADIOMICS ANALYSIS FOR SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1242.2-1243
Author(s):  
J. Schniering ◽  
M. Maciukiewicz ◽  
H. Gabrys ◽  
M. Brunner ◽  
C. Blüthgen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Correlation Analysis ◽  
Lung Disease ◽  
Roc Curve ◽  
Wilcoxon Test ◽  
Grey Level ◽  
Research Support ◽  
Long Run

Background:Interstitial lung disease (ILD) affects 60% of patients with systemic sclerosis (SSc) and is the primary cause of death. Medical imaging is an integral part of the routine work-up for diagnosis and monitoring of SSc-ILD and includes high-resolution computed tomography (HRCT). Radiomics is a novel research area that describes the in-depth analysis of tissue phenotypes in medical images with computational retrieval of quantitative, mineable metadata appropriate for statistical analyses.Objectives:To explore the performance of HRCT-derived radiomic features for the assessment of SSc-associated ILD (i.e. diagnosis, staging, and lung function).Methods:Radiomics analysis was performed on HRCT scans from 98 SSc patients, including n=33 SSc patients without ILD, n=33 with limited and n=32 with extensive ILD as defined by 0%, <20% and ≥20% visual extent of fibrosis on HRCT, respectively. Following semi-automated segmentation of lung tissue on 3D reconstructed HRCT scans, 1386 radiomic features, including 17 intensity, 137 texture, and 1232 wavelet features were extracted using the in-house developed software Z-Rad (Python 2.7). In order to identify robust features, we conducted intra- and inter-reader correlation analysis (ICC) in a subgroup of patients. Only features with good reproducibility (ICC ≥ 0.75) entered subsequent analyses. We applied the Wilcoxon test, followed by Receiver Operating Characteristic ROC) curve analyses, to identify features significantly different between a) ILD and non-ILD and b) limited vs. extensive ILD patients. Spearman rank correlation was performed to reveal significant associations of radiomic features from a) and b) with lung function as measured by percentage of predicted forced vital capacity (FVC% predicted).Results:In total, 1355/1386 radiomic features passed the test of robustness and were eligible for further, exploratory analyses. Radiomic features with good performance (area under the ROC curve (AUC) ≥ 0.7 and p-value ≤ 0.05) were considered as potential candidate discriminators. Under this criterion, we identified 288/1355 (21.3%) radiomic features that were significantly different between ILD and non-ILD patients and 409/1355 (30.2%) features that significantly discriminated between limited and extensive ILD (Fig. 1). For diagnosis, the texture featuredependence count entropywas the top parameter to distinguish ILD patients from healthy controls (AUC = 0.89, p = 1.83x10-10), whereas for staging the wavelet featureHHH long run high grey level emphasisproved to be best suited to separate limited from extensive ILD (AUC = 0.88, p = 7.76x10-9).Fig 1.Correlation analysis of the most significant (best performing) discriminative radiomic features with lung function revealed a significant negative correlation ofdependence count entropy(rho = -0.51, p = 9.89x10-8) andHHH long run high grey level emphasis(rho = -0.51, p = 1.73x10-5) with FVC% predicted.Conclusion:Our study adds novelty to the field of SSc-ILD showing that radiomic features have great potential as quantitative imaging biomarkers for diagnosis and staging of SSc-ILD and that they may reflect lung function. As the next step, we are planning to build predictive models, using machine learning, for diagnosis, staging, and lung function and validate them in external patient cohorts. If validated such models will pave the way for computer-aided management in SSc-ILD and thus improve patients’ outcome.References:[1]Gillies, R. J., Kinahan, P. E. & Hricak, H. Radiomics: Images Are More than Pictures, They Are Data. Radiology 278, 563-577, doi:10.1148/radiol.2015151169 (2016).Disclosure of Interests:Janine Schniering: None declared, Malgorzata Maciukiewicz: None declared, Hubert Gabrys: None declared, Matthias Brunner: None declared, Christian Blüthgen: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Matthias Guckenberger: None declared, Thomas Frauenfelder: None declared, Stephanie Tanadini-Lang: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis

scholarly journals SAT0286 BIOLOGICAL CORRELATES OF RADIOGRAPHIC FEATURES OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS: AN IN DEPTH ANALYSIS OF BRONCHOALVEOLAR PROTEINS OF SCLERODERMA LUNG STUDY I PARTICIPANTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1087.1-1088
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
N. Li ◽  
G. Kim ◽  
J. Goldin ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Research Support ◽  
Radiographic Features ◽  
Depth Analysis ◽  
Specific Proteins ◽  
Clinical Measures ◽  
The Relationship

Background:Systemic sclerosis-related interstitial lung disease (SSc-ILD) involves a combination of inflammation, fibrosis and vascular pathology that is typically assessed on CT imaging as a mixture of ground-glass opacification (GGO) and fibrotic changes. We hypothesized that proteins recovered from bronchoalveolar lavage (BAL) could be used to probe the underlying pathobiology associated with GGO and fibrotic changes.Objectives:(1) To assess the relationship between 68 unique BAL proteins measured in participants of Scleroderma Lung Study (SLS) I1and radiographic and physiologic measures of ILD; (2) To identify inter-correlations among specific proteins to enlighten our understanding of how specific biological pathways contribute to SSc-ILD.Methods:Bronchoscopy was performed on 144 of the 158 participants in SLS I with 103 BAL samples available for analysis. BAL was lyophilized, concentrated 10X and used in a multiplex protein analysis for 68 different cytokines, chemokines and other factors. Kendall tau correlations were performed to assess the relationship between individual proteins and baseline measures of pulmonary function and quantitative CT scores for fibrosis, GGO and total ILD. Those proteins found to correlate significantly with at least 2 clinical measures of ILD were entered into a cluster analysis with inter-correlations expressed as a heatmap.Results:Significant correlations were observed between fibrosis scores and several biologic pathways including pro-fibrotic factors (transforming growth factor beta [TGF-β], platelet-derived growth factor [PDGF]), proteins involved in tissue remodeling (Matrix metallopeptidase [MMP]-1,7,8,9; Hepatocyte growth factor [HGF]), and those involved in monocyte/macrophage migration and activation (Monocyte chemoattractant protein [MCP]-1,3; macrophage colony-stimulating factor [MCSF]). These same pathways correlated with the diffusing capacity for carbon monoxide (DLCO). In contrast, GGO scores correlated primarily with immune and inflammatory mediators (interleukin [IL]-5,8,13,15, IL-1 receptor antagonist and interferon gamma) with only limited overlap to proteins that related to fibrosis. Vascular endothelial growth factor (VEGF) levels were lower in patients with more extensive GGO, fibrosis and diffusion impairment, suggesting that vascular changes are a central feature of SSc-ILD. Specific proteins were highly correlated with one another in a pattern suggesting biologically-related networks (Figure) that might provide additional insight regarding disease pathogenesis.Conclusion:Combining a diverse analysis of BAL proteins with the rich dataset available from SSc-ILD patients participating in SLS I, the study findings suggest the involvement of distinct biologic pathways, inter-related networks, and specific biologic signatures associated with unique radiographic features of ILD. The relationship of these factors to other SSc disease features, patient outcomes and as predictors of treatment responses will be studied in future analyses.References:[1]Tashkin DP, et al. NEJM 2006.Figure.Correlation heatmap of BAL proteins associated with at least 2 clinical measures of ILD in SSc patients. Absolute correlations are depicted, and darker colors signify stronger correlations.Disclosure of Interests:Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Donald Tashkin: None declared, Ning Li: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Airi Harui: None declared, Michael Roth Grant/research support from: Genentech/Roche

scholarly journals OP0268 TREATMENT STATUS AFFECTS HOW PULMONARY BIOMARKERS PREDICT PROGRESSION OF SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 163.1-163
Author(s):  
E. Volkmann ◽  
D. Tashkin ◽  
M. Leng ◽  
N. LI ◽  
G. Kim ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Transforming Growth Factor ◽  
Selection Process ◽  
Linear Regression Models ◽  
Research Support ◽  
Gm Csf ◽  
Treatment Status

Background:The course of interstitial lung disease (ILD) varies considerably in patients with systemic sclerosis (SSc), and no biomarkers have been found to consistently predict ILD progression in this population. Treatment may affect how a candidate biomarker correlates with improvement/worsening of SSc-ILD. We hypothesized that specific proteins recovered from bronchoalveolar lavage (BAL) would differentially predict progression of SSc-ILD based on whether a patient was receiving ILD therapy.Objectives:(1) To assess the relationship between 68 unique BAL proteins measured in participants of Scleroderma Lung Study (SLS) I1 and changes in radiographic extent of SSc-ILD; (2) To determine if treatment affects whether a specific protein predicts improvement or worsening of SSc-ILD.Methods:Bronchoscopy was performed on 144 of the 158 participants in SLS I (Cyclophosphamide [CYC] vs. placebo) with 103 BAL samples available for analysis. BAL was lyophilized, concentrated 10X and used in a multiplex protein analysis of 68 distinct cytokines, chemokines and growth factors. Quantitative imaging analysis (QIA) was used to calculate the extent of radiographic fibrosis (QLF) in the whole lung using HRCT of the chest at baseline and 12 months. Multivariable linear regression models were created to determine the key BAL proteins associated with change in QLF scores using a backward selection process adjusting for treatment arm and ILD severity. The bootstrap procedure was employed for internal validation.Results:A number of BAL proteins were significantly associated with change in QLF scores at 12 months; however, the directionality of these associations was often based on the presence/absence of treatment. For example, increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, monocyte chemoattractant protein (MCP)-3, chemokine ligand (CCL)-5, transforming growth factor (TGF)-β, hepatocyte growth factor (HGF), stem cell factor (SCF), IL-4, TGF-α, were associated with worse QLF scores in patients who received placebo; whereas, increased levels of these same proteins were associated with improved QLF scores in patients who received CYC (Figure). Increased levels of Fractalkine were associated with worse in QLF scores, and increased levels of IL-7 were associated with improved QLF scores, regardless of treatment arm. In the multivariable model adjusting for treatment arm and baseline severity of ILD, IL-1, MCP-3, surfactant protein C, IL-7, and CCL-5 were independently associated with change in QLF scores.Figure 1.Example of a specific BAL protein (GM-CSF) that predicts worse QLF scores in patients receiving placebo (Group B, Red dotted line) and improved QLF scores in patients receiving CYC (Group A, Blue solid line). Shaded areas represent 95% confidence intervals.Conclusion:Proteins that mediate both inflammation and fibrosis differentially affected progression of SSc-ILD based on treatment status. Higher levels of certain proteins predicted worsening of ILD in patients receiving placebo, but improvement in patients receiving CYC. Measuring these proteins could help to identify patients who: (1) are at risk for ILD progression, and (2) may preferentially benefit from treatment with immunosuppression.References:[1]Tashkin DP, et al. NEJM 2006.Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Donald Tashkin: None declared, Mei Leng: None declared, Ning Li: None declared, Grace Kim: None declared, Jonathan Goldin: None declared, Airi Harui: None declared, Michael Roth Grant/research support from: Genentech/Roche

scholarly journals POS0866 TWO-DIMENSIONAL HRCT-BASED RADIOMIC FEATURES IN SSC-ILD DISTINGUISH DRUG RESPONDERS FROM NON-RESPONDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 688-689
Author(s):  
C. Meier ◽  
M. Maciukiewicz ◽  
M. Brunner ◽  
J. Schniering ◽  
H. Gabrys ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Linear Regression ◽  
Lung Disease ◽  
Treatment Response ◽  
Two Dimensional ◽  
Research Support ◽  
Pre Treatment

Background:Management of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is complicated by high inter-patient variability. To date, no validated predictors of treatment response are available for routine use. High resolution computed tomography (HRCT)-based radiomics, i.e. the high-dimensional, quantitative analysis of imaging metadata, have previously been shown to be successful in discriminating (SSc-)ILD phenotypes in preclinical and clinical studies1. Since HRCT is an integral part of the routine work-up in SSc, HRCT-based radiomic features may hold potential as non-invasive biomarkers.Objectives:To predict treatment response using two-dimensional (2D) HRCT-based radiomics in SSc-ILD patients from a prospectively followed cohort.Methods:Inclusion criteria were diagnosis of SSc-ILD in HRCT, availability of a suitable chest HRCT scan within 12 months prior to initiation of a new treatment, and availability of clinical baseline and follow-up information. Treatment response was defined as the absence of all of the following over a follow-up period of 12-24 months: relative decrease in forced vital capacity (FVC) ≥5%, increase of ILD in HRCT as assessed by a radiologist, change in treatment regimen due to insufficient response, ILD-related death or lung transplantation. Of each pre-treatment HRCT, 6 slices (15±5 mm apart, starting from the basal lung margin) were manually segmented and 1513 2D radiomic features were extracted using the in-house software Z-Rad (Python 2.7). Features were Z-score transformed and pre-filtered for inter- and intra-reader robustness (intraclass correlation coefficient >0.85) and inter-feature correlation (Spearman’s rho <0.9). A categorical linear regression model was created using 3-fold cross-validated elastic nets for feature selection. Features were then summarized and divided by their number. For generation of a score cut-off, Youden’s score was used. For two-group analyses of continuous variables, Wilcoxon’s test was performed, whereas categorical data was assessed using Fisher’s exact test.Results:A total of 64 pre-treatment HRCTs from 54 patients were analyzed. In 9 patients, >1 asynchronous treatments were assessed, while 45 patients had only 1 eligible treatment approach. The response rate within the assessed follow-up period was 45.3% (n=29). For score generation, 13 radiomic features were selected and an optimal cut-off value of -0.1589 was determined. Univariate linear regression showed significant association between our categorical radiomics-based score and treatment response (p=0.007, area under the curve = 0.65 (0.51-0.79), sensitivity=0.90, specificity=0.43), whereby a high score was predictive for treatment response.No differences between patients with high (n=46) or low (n=18) scores were detected for baseline age (mean±SD=55.5±12.0 and 55.5±13.6 years, p=0.84), duration of SSc (mean±SD=6.2±8.4 and 4.7±4.4 years, p=0.79), time since ILD diagnosis (2.7±2.9 and 2.4±3.1 years, p=0.59), FVC (77.6±20.6 and 80.1±17.9, p=0.41) or DLco (54.4±21.0 and 57.6±18.9, p=0.40). Distribution of anti-Scl-70 positivity (45.7% vs. 55.6%, p=0.58) and diffuse cutaneous disease (47.7% vs. 61.1%, p=0.41) was not significantly different between patients with high and low scores, respectively, although a trend towards higher percentages in the high score group was observed.Conclusion:Our results indicate that, following validation in external cohorts, radiomics may be a promising tool for future pre-treatment patient stratification. Moreover, our radiomics-based score seems not to be associated with commonly studied clinical predictors such as anti-Scl-70 positivity or lung function, underlining a possible additive value to ‘traditional’ clinical parameters.References:[1]Schniering, J., et al. Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics. medRxiv [Preprint] doi:10.1101/2020.06.09.20124800 (2020).Disclosure of Interests:Chantal Meier: None declared, Malgorzata Maciukiewicz: None declared, Matthias Brunner: None declared, Janine Schniering: None declared, Hubert Gabrys: None declared, Anja Kühnis: None declared, Oliver Distler Speakers bureau: Speaker fee on Scleroderma and related complications: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche. Speaker fee on rheumatology topic other than Scleroderma: MSD, iQone, Novartis, Pfizer, Roche, Consultant of: Consultancy fee for Scleroderma and its complications: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Horizon Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Roivant Sciences, Sanofi, UCB. Consultancy fee for rheumatology topic other than Scleroderma: Abbvie, Amgen, Lilly, Pfizer, Grant/research support from: Research Grants to investigate the pathophysiology and potential treatment of Scleroderma and its complications: Kymera Therapeutics, Mitsubishi Tanabe, Thomas Frauenfelder: None declared, Stephanie Tanadini-Lang: None declared, Britta Maurer Speakers bureau: Speaker fees from Boehringer-Ingelheim, Grant/research support from: Grant/research support from AbbVie, Protagen, Novartis Biomedical Research, congress support from Pfizer, Roche, Actelion, mepha, and MSD

scholarly journals Impact of Lung Function Decline on Time to Hospitalisation Events in Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD): a Joint Model Analysis

2021 ◽  
Author(s):  
Michael Kreuter ◽  
Francesco Del Galdo ◽  
Corinna Miede ◽  
Dinesh Khanna ◽  
Wim A. Wuyts ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Fold Increase ◽  
Phase Iii ◽  
Lung Function Decline ◽  
Related Hospitalisation ◽  
The Relationship ◽  
Increase In Risk

Abstract Background: Interstitial 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.Methods: We 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.Results: There 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®.Conclusions: The 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 registration: Clinialtrials.gov, NCT02597933. Registered 8 October 2015, https://clinicaltrials.gov/ct2/show/study/NCT02597933.

scholarly journals Lung Function and Survival in Systemic Sclerosis Interstitial Lung Disease

2014 ◽  
Vol 41 (11) ◽  
pp. 2326-2328 ◽  
Author(s):  
SAMAR SHADLY AHMED ◽  
SINDHU R. JOHNSON ◽  
CHRISTOPHER MEANEY ◽  
CATHY CHAU ◽  
THEODORE K. MARRAS
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease

FRI0254 The Effect of Cyclophosphamide on Lung Function in Different Stages of Interstitial Lung Disease Associated To Systemic Sclerosis: Table 1.

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 526.1-526
Author(s):  
W.M.T. Van Den Hombergh ◽  
E. Teesselink ◽  
H.K.A. Knaapen-Hans ◽  
S.O. Simons ◽  
F.H.J. van den Hoogen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease

scholarly journals Predictors of lung function test severity and outcome in systemic sclerosis-associated interstitial lung disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0181692 ◽  
Author(s):  
Noémie Le Gouellec ◽  
Alain Duhamel ◽  
Thierry Perez ◽  
Anne-Lise Hachulla ◽  
Vincent Sobanski ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Lung Function Test ◽  
Function Test

scholarly journals POS0858 POTENTIAL EFFICACY PREDICTORS OF ANTI-B-CELL THERAPY IN THE PATIENTS WITH SYSTEMIC SCLEROSIS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 683.2-684
Author(s):  
O. Koneva ◽  
L. P. Ananyeva ◽  
L. Garzanova ◽  
O. Desinova ◽  
O. Ovsyannikova ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Correlation Analysis ◽  
Cell Therapy ◽  
Lung Disease ◽  
B Cell ◽  
Disease Duration ◽  
Potential Efficacy ◽  
Group A ◽  
Group B

Background:Rituximab (RTM) is considered as a promising therapeutic agent for treatment of With Interstitial Lung Disease (ILD) in the patients with systemic sclerosis (SSc). However, the limited number of RTM-treated patients, considerably varying dose regimens, cumulative doses and observation periods, lack of data on potential predictors of RTM therapy response do not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc.Objectives:The study of potential efficacy predictors of anti-B-cell therapy in the patients with SSc associated with ILD.Methods:90 patients with SSc-ILD verified by multispiral computed tomography were enrolled to the study and received RTM therapy for 12-42 months at cumulative dose 2.9±1.1 grams (disease duration 5.9±4.8 years, diffused/limited SSc 1.3/1, average age 47 ± 13.6 years, females 83%). All patients received low or moderate dose glucocorticoids. 45 patients received RTM in addition to immunosuppressive therapy (cyclophosphamide and mycophenolate mofetil) because of inadequate efficacy of immunosuppressants. After evaluation of FVC trends in the patients receiving RTM the overall study population was divided into two patient groups for the analysis: group A (n=35) comprised the patients with ≥10% FVC increase (disease duration 6.1±5.8 years, diffused/limited SSc 1,3/1, average age 50±12 years, females 86%, cumulative RTM dose 3.2±1.24 grams), and group B (n=11) comprised the patients with ≥5% FVC decrease (disease duration 5.2±4, diffused/limited SSc 0.8/1, average age 43±16, females 72%, cumulative RTM dose 2.5±0.99 grams). Subsequently correlation analysis was made to clarify the association between delta FVC and a number of clinical (age, gender, duration and form of SSc, modified skin count, presence of gastroesophageal reflux, mPAP, SSc activity (EScSG, points), cumulative RTM dose, immunosuppressive therapy) and laboratory parameters (ESR, ANA-НЕР-2, a-Scl-70, CRP, B cell count).Results:In the overall patient population RTM therapy was associated with significant FVC increase from 77.0±19.9 % to 84.7±20.9% (р=0.000000), with median FVC increment 6.6% [0;14.1].In group A FVC increased from 75.3±19.9 to 94.3±20.4) (р=0.000000), with median FVC increment 16.3 [12.6; 24.7].In group B FVC decreased from 82.5 ±23.2 to 72,3±19.4 (р=0,000176), with median FVC decrement 10.4% [-13.4; -6].Correlation analysis in groups A and B showed significant association of between delta FVC and the patient age (R=0.36), cumulative RTM dose (R=0.34) and EScSG during the last examination (1.2±.,0 and 3.1±1.4 in groups A and B, respectively; R=-0.42).No significant correlation between delta FVC and any other tested parameters was found.Conclusion:Therefore, older patients who received the cumulative rituximab dose more than 3 grams with suppressed SSc activity achieved greater FVC increase at the background of therapy. These data allow to consider the above parameters as potential predictors of response to anti-B-cell therapy in the patients with SSc-ILD.Disclosure of Interests:None declared

Sign in / Sign up

Export Citation Format

Share Document