scholarly journals Association between immunosuppressive therapy and course of mild interstitial lung disease in systemic sclerosis

Rheumatology ◽  
2019 ◽  
Vol 59 (5) ◽  
pp. 1108-1117 ◽  
Author(s):  
Sabrina Hoa ◽  
Sasha Bernatsky ◽  
Russell J Steele ◽  
Murray Baron ◽  
Marie Hudson ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Disease Duration ◽  
Immunosuppressive Drugs ◽  
Baseline Visit ◽  
Impaired Lung Function ◽  
Risk Of Progression ◽  
One Year ◽  
The One

Abstract Objective Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Little is known about the benefits of immunosuppressive drugs in mild ILD. Our aim was to determine whether use of CYC or MMF was associated with an improved ILD course in patients with normal or mildly impaired lung function. Methods A retrospective cohort of SSc subjects with ILD, disease duration below seven years and no exposure to CYC or MMF prior to the baseline visit was constructed from the Canadian Scleroderma Research Group registry. Subjects were categorized as having mild ILD if baseline forced vital capacity (FVC % predicted) was >85%. The primary exposure was any use of CYC or MMF at the baseline visit. FVC at one year was compared between exposed and unexposed subjects, using multivariate linear regression. Results Out of 294 eligible SSc-ILD subjects, 116 met criteria for mild ILD. In this subgroup, mean (s.d.) disease duration was 3.7 (2.0) years. Thirteen (11.2%) subjects were exposed to CYC or MMF at baseline. The one-year FVC was higher in exposed subjects compared with unexposed subjects, by a difference of 8.49% (95% CI: 0.01–16.98%). None of the exposed subjects experienced clinically meaningful progression over two years, whereas 24.6% of unexposed subjects did. Conclusion In this real-world setting, CYC/MMF exposure at baseline was associated with higher FVC values and a lower risk of progression among subjects with mild ILD. These data suggest a window of opportunity to preserve lung function in SSc-ILD.

Lung function trajectory in progressive fibrosing interstitial lung disease

2021 ◽  
pp. 2101396
Author(s):  
Justin M. Oldham ◽  
Cathryn T. Lee ◽  
Zhe Wu ◽  
Willis S. Bowman ◽  
Janelle Vu Pugashetti ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Trial Design ◽  
Cohort Analysis ◽  
Clinical Trial Design ◽  
Joint Modeling ◽  
Therapeutic Trials ◽  
One Year

Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criterion remains unknown. Because survival is rarely employed as the primary endpoint in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design. A retrospective, multi-center longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centers (test cohort) and one UK center (validation cohort). One-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modeling. Subgroup analyses were performed to determine whether results varied across key subgroups. One thousand two hundred twenty-seven patients were included, with CTD-ILD predominating. Six of nine PF-ILD criteria were associated with differential one-year change in FVC, with radiologic progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiologic pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype. These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.

scholarly journals POS0645 RITUXIMAB THERAPY IN THE INTERSTITIAL LUNG DISEASE OF RHEUMATOID ARTHRITIS: A SYSTEMATIC REVIEW

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 560.3-561
Author(s):  
E. F. Vicente-Rabaneda ◽  
J. De la Macorra ◽  
J. P. Baldivieso ◽  
F. Gutiérrez-Rodríguez ◽  
A. García-Vadillo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Adverse Events ◽  
Lung Disease ◽  
Statistical Significance ◽  
Connective Tissue Diseases ◽  
Case Series ◽  
Original Research ◽  
Case Control Studies

Background:Interstitial lung disease (ILD) is a severe manifestation of rheumatoid arthritis (RA), linked to increased mortality. There is still no consensus on the best therapeutic strategy as there aren’t yet randomized controlled trials.Objectives:To analyze the available scientific evidence on the efficacy and safety of rituximab (RTX) treatment of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA).Methods:A systematic search was carried out in PubMed until April 2020 following the PRISMA recommendations. Studies were selected according to the following inclusion criteria: (1) original research, including case series, case/control studies, cohort studies, and clinical trials; (2) population with RA and associated ILD, either monographically or together with other connective tissue diseases (CTD), provided that individualized data on patients with RA were provided; (3) patients treated with RTX; (4) objective and quantifiable results on the evolution of ILD after treatment with available data of FVC, DLCO and/or HRCT.Results:Of the 64 papers identified, 9 articles were selected. The studies showed great heterogeneity in design, both in the sample selection criteria and in the objectives of the analysis. Most were observational, retrospective (n = 6) or prospective (n = 2) studies, with only one open prospective experimental study. Those focused on RA predominated, but 3 of them also included patients with other CTDs. The mean age of the patients in the different studies ranged between 52 and 70 years, predominantly women. 40-79% had a history of smoking and were mostly positive for rheumatoid factor (83-100%) and anti-CCP (82-100%). The most frequent radiological patterns were NSIP, UIP and undefined. The outcome measures were diverse: changes in respiratory function tests (LTF) and HRCT, incidence of pulmonary dysfunction, mortality rates, effect on glucocorticoid deprivation, delay in inclusion in the lung transplant list and/or serious adverse events. The initiation of RTX was motivated by pulmonary and/or joint pathology, in patients with failure to other synthetic or biological DMARDs. A total of 393 treatment cycles were collected in 114 patients, with a mean of 3.45 cycles per patient. The RTX regimen was 2 infusions of 1g 2 weeks apart in all patients, except for 1 who received the lymphoma-like regimen. With regard to the efficacy of the treatment with RTX, improvement and especially stabilization of HRCT and LFT predominated, with numerically greater improvement for DLCO than for FVC. There was also a favorable trend in the evolution of patients treated with RTX compared to controls, although it did not reach statistical significance, and a lower risk of deterioration of lung function in patients treated with RTX versus those who had received other DMARDs. The mortality rate found at 5 years was lower than that previously described for the disease and half for the patients treated with RTX compared to those treated with anti-TNF. The adverse events described in the studies did not show additional safety alerts to those already described for RTX.Conclusion:RTX seems to be postulated as a promising therapy for patients with ILD associated with RA, showing a stabilizing effect on the lung function, with an acceptable safety profile. However, further research of higher methodological quality prospective studies is needed to confirm these favorable preliminary results.Disclosure of Interests:None declared

scholarly journals OP0009 DERIVATION AND VALIDATION OF THE SCLERODERMA LUNG 3-STAGE INDEX (SL3SI), A NEW FUNCTIONAL INDEX FOR INTERSTITIAL LUNG DISEASE WITH PROGNOSTIC IMPLICATIONS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 7.2-7
Author(s):  
A. Santaniello ◽  
C. Bellocchi ◽  
L. Bettolini ◽  
M. Cassavia ◽  
G. Montanelli ◽  
...  
Keyword(s):  
At Risk ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Disease Severity ◽  
Disease Duration ◽  
Functional Model ◽  
Severity Scale ◽  
Predictive Capability ◽  
Patients At Risk ◽  
Disease Severity Scale

Background:The staging of interstitial lung disease (ILD) is important to monitor disease progression and for prognostication. A disease severity scale of Systemic Sclerosis (SSc)-related lung disease has long been proposed (i.e. Medsger’s severity scale). This scale was mostly developed by discussion and consensus and stage thresholds were not computed by a data-driven approach. Hidden Markov models (HMM) are methods to estimate population quantities for chronic diseases with a staged interpretation which are diagnosed by markers measured at irregular intervals.Objectives:To build a SSc-ILD specific disease severity scale with prognostic relevance via HMM modeling.Methods:A total of 358 SSc patients at risk for or with ILD were enrolled in a discovery (207 cases, Milan1) and in a validation (151 cases, Milan2, Pavia and Rome) cohort. Patients were included if satisfied the following criteria: 1) Diagnosis of SSc according to the EULAR/ACR 2013 criteria, 2) absence of anticentromere antibodies, 3) dcSSc subset or 4) other subsets with either 4a) ILD-related antibodies (Scl70, PmScl, Ku) or 4b) evidence of ILD on HRCT, 5) disease duration < 5 years at the time of the first pulmonary function test (PFT). Serial PFTs were retrieved and the time up to the last available visit -if the patient alive-, or to death due to pulmonary complications, was recorded. HMM were used to estimate the threshold of a 3-stage model (SL3SI, Scleroderma Lung 3-Stage Index) based on PFT functional values (normal/mild, moderate, severe involvement) in the discovery cohort. Survival estimates of the SL3SI model were compared to Medsger’s severity classes estimates and their predictive capability evaluated via the explained residual variation (R2) of prediction errors (the higher the better). One-hundred random replicates were generated to simulate the prediction effort in patients with different disease duration and lung severity.Results:Patients characteristics are summarized in the Table. Fifteen-years survival estimates for Mesdger’s classes in the discovery set were: normal=0.88, mild=0.86, moderate=0.84 and severe=0.71. The SL3SI was defined by the following thresholds: normal/mild, FVC and DLco >=75%; moderate FVC or DLco 74-55%; severe, FVC or DLco <55%. SL3SI 15-yrs survival estimates were: normal/mild=0.89, moderate=0.82 and severe=0.63. Prediction analysis showed a higher R2values at 15 yrs for the SL3SI compared to Medsger’s classes, providing evidence for a better predictive capability of the former (discovery: 0.31 vs 0.25; validation: 0.28 vs 0.19).Conclusion:The SL3SI, a simplified 3-stage functional model of SSc-ILD, yields better survival estimates and long-term prognostic information than Medsger’s classes. Its reproducibility and ease of use make it a useful tool for the functional and prognostic evaluation of SSc patients at risk for or with ILD.Table:VariablesDiscovery (n=207)Replication (n=151)DcSSc62 (30%)98 (64%)Age at first PFR48.6±1249.1±14.4Disease duration at first PFR1.7±1.61.3±2.4FVC90.5±18.191.1±20.2DLco70.7±19.861.3±20.1ILD on HRCT179 (86%)125 (80%)Scl70157 (76%)153 (78%)SSA63 (30%)32 (21%)n of visits38571473Follow-up time, yrs11±5.610.6±5.7Deaths27 (13%)23 (15%)Disclosure of Interests:Alessandro Santaniello: None declared, Chiara Bellocchi: None declared, Luca Bettolini: None declared, Marcello Cassavia: None declared, Gaia Montanelli: None declared, Adriana Severino: None declared, Monica Caronni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Paolo Delvino: None declared, Claudio Tirelli: None declared, Lorenzo Cavagna: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Silvia Laura Bosello: None declared, Lorenzo Beretta Grant/research support from: Pfizer

AB0796 THE EVALUATION OF LUNG DIAGNOSTIC PROCEDURE AT THE ONSET OF INFLAMMATORY RHEUMATIC DISEASES WITH INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1422.3-1423
Author(s):  
T. Hoffmann ◽  
P. Oelzner ◽  
F. Marcus ◽  
M. Förster ◽  
J. Böttcher ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Sensitivity And Specificity ◽  
Lung Function Test ◽  
Inflammatory Rheumatic Diseases ◽  
X Ray ◽  
Function Test ◽  
Chest X Ray

Background:Interstitial lung disease (ILD) in inflammatory rheumatic diseases (IRD) is associated with increased mortality. Moreover, the lung is one of the most effected organs on IRD. Consequently, screening methods were required to the detect ILD in IRD.Objectives:The objective of the following study is to evaluate the diagnostic value of lung function test, chest x-ray and HR-CT of the lung in the detection of ILD at the onset of IRD.Methods:The study is designed as a case-control study and includes 126 patients with a newly diagnosed IRD. It was matched by gender, age and the performance of lung function test and chest x-ray. The sensitivity and specificity were verified by crosstabs and receiver operating characteristic (ROC) curve analysis. The study cohort was divided in two groups (ILD group: n = 63 and control group: n = 63). If possible, all patients received a lung function test and optional a chest x-ray. Patients with pathological findings in the screening tests (chest x-ray or reduced diffusing capacity for carbon monoxide (DLCO) < 80 %) maintained a high-resolution computer tomography (HR-CT) of the lung. Additionally, an immunological bronchioalveolar lavage was performed in the ILD group as gold standard for the detection of ILD.Results:The DLCO (< 80 %) revealed a sensitivity of 83.6 % and specificity of 45.8 % for the detection of ILD. Other examined parameter of lung function test showed no sufficient sensitivity as screening test (FVC = Forced Vital Capacity, FEV1 = Forced Expiratory Volume in 1 second, TLC = Total Lung Capacity, TLCO = Transfer factor of the Lung for carbon monoxide). Also, a combination of different parameter did not increase the sensitivity. The sensitivity and specificity of chest x-ray for the verification of ILD was 64.2 % versus 73.6 %. The combination of DLCO (< 80 %) and chest x-ray showed a sensitivity with 95.2 % and specificity with 38.7 %. The highest sensitivity (95.2 %) and specificity (77.4 %) was observed for the combination of DLCO (< 80 %) and HR-CT of the lung.Conclusion:The study highlighted that a reduced DLCO in lung function test is associated with a lung involvement in IRD. DLCO represented a potential screening parameter for lung manifestation in IRD. Especially patients with suspected vasculitis should receive an additional chest x-ray. Based on the high sensitivity of DLCO in combination with chest x-ray or HR-CT for the detection of ILD in IRD, all patients with a reduced DLCO (< 80%) should obtained an imaging of the lung.Disclosure of Interests:None declared

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 Biomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1534-1546 ◽  
Author(s):  
Olivier Bonhomme ◽  
Béatrice André ◽  
Fanny Gester ◽  
Dominique de Seny ◽  
Catherine Moermans ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Wide Spectrum ◽  
Unknown Origin ◽  
Multiple Organ ◽  
Correct Identification ◽  
Review Of The Literature ◽  
Clinical Value ◽  
Diagnosis And Prognosis ◽  
Risk Of Progression

Abstract SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classified according to the different biological pathways involved. The purpose of this article is to describe the main biomarkers thought to be of interest with clinical value in the diagnosis and prognosis of SSc-interstitial lung disease.

scholarly journals Determinants of health-related quality of life decline in interstitial lung disease

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Phillen Nozibuyiso Maqhuzu ◽  
Boglarka L. Szentes ◽  
Michael Kreuter ◽  
Thomas Bahmer ◽  
Nicolas Kahn ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Psychological Impact ◽  
Health Related Quality ◽  
Lower Baseline ◽  
Related Quality ◽  
Health Related

Abstract Background Health-related quality of life (HRQL) in interstitial lung disease (ILD) patients is impaired. We aimed to identify baseline predictors for HRQL decline within a 12-month observation period. Methods We analyzed 194 ILD patients from two German ILD-centers in the observational HILDA study. We employed the disease-specific King’s Brief Interstitial Lung Disease questionnaire (K-BILD) with the subdomains ‘psychological impact’, ‘chest symptoms’ and ‘breathlessness and activities’, and the generic EQ-5D Visual Analog Scale (VAS). We evaluated how many patients experienced a clinically meaningful decline in HRQL. Subsequently, we investigated medical and sociodemographic factors as potential predictors of HRQL deterioration. Results Within the study population (34.0% male, Ø age 61.7) mean HRQL scores hardly changed between baseline and follow up (K-BILD: 52.8 vs. 52.5 | VAS: 60.0 vs. 57.3). On the intra-individual level, 30.4% (n = 59) experienced a clinically relevant deterioration in K-BILD total score and 35.4% (n = 68) in VAS. Lower baseline forced vital capacity (FVC) % predicted determined HRQL decline in K-BILD total score (ß-coefficient: − 0.02, p = 0.007), VAS (ß-coefficient: − 0.03, p < 0.0001), and in the subdomain ‘psychological impact’ (ß-coefficient: − 0.02, p = 0.014). Lower baseline diffusing capacity of carbon monoxide (DLCO) % predicted determined deterioration in ‘breathlessness and activities’ (ß-coefficient: − 0.04, p = 0.003) and ‘chest symptoms’ (ß-coefficient: − 0.04, p = 0.002). Additionally, increasing age predicted decline in ‘psychological impact’ (ß-coefficient: 0.06, p < 0.007). Conclusion Around a third of ILD patients experienced a clinically relevant HRQL deterioration in a 12-month period, which was associated with baseline lung function values in all K-BILD domains. As lung function values are time-dependent variables with possible improvements, in contrast to age and ILD subtype, it, thus, seems important to improve lung function and prevent its decline in order to maintain HRQL on the possibly highest level.

Sign in / Sign up

Export Citation Format

Share Document