AB0584 DOES ANTI-ACID TREATMENT INFLUENCE DISEASE PROGRESSION IN SYSTEMIC SCLEROSIS INTERSTITIAL LUNG DISEASE (SSC-ILD)? DATA FROM THE GERMAN SSC-NETWORK

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1589-1589
Author(s):  
M. Kreuter ◽  
F. Bonella ◽  
G. Riemekasten ◽  
U. Müller-Ladner ◽  
J. Henes ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Disease Progression ◽  
Acid Treatment ◽  
Current Analysis ◽  
Research Support ◽  
Steroid Use ◽  
Acid Therapy ◽  
Scientific Support ◽  
Significant Difference ◽  
Baseline Characteristics

Background:Gastroesophageal reflux (GER) is common in SSc and thus treatment with anti-acid therapy (AAT) is frequent. An association between GER and the development / progression of SSc-ILD has been hypothesized. However, outcomes of AAT on disease progression in SSc-ILD has only sparsely been studied.Objectives:Methods:The German Network for Systemic Scleroderma (DNSS), which includes SSc pts. prospectively, was analyzed for SSc-ILD. Those without progression at ILD 1stdiagnosis were categorized in AAT vs. no-AAT users and disease outcome was assessed.Results:SSc-ILD was reported in 1165 (28.2%) out of 4131 pts. 712 of SSc-ILD pts had no disease progression at ILD 1stdiagnosis. 567 used AAT while 145 did not. Baseline characteristics were similar between groups with regards to age (mean 54.7 years), BMI, time since SSc diagnosis and immunosuppressant use. Significant differences in no-AAT vs. AAT were found for gender (male 18% vs. 25%, p=0.05), SSc subtype (p=0.002, diffuse more common in AAT), lung function (DLCO 66% vs. 58%, p=0.001; FVC 86% vs. 77%, p=0.001), mRSS (8 vs. 11.5, p<0.01), esophageal involvement (32% vs. 56%, p<0.01) and steroid use (30% vs. 43%, p=0.005). While mortality did not differ between groups (3.9%, p= 0.59), disease progression was more common in the AAT group than in no-AAT users (24.5% vs. 13%, p=0.03). Furthermore, there was a significant difference in decline of FVC≥10% with 30% in the AAT compared to 14% in no-AAT (p=0.018); a decline in DLCO≥15% was more common in the AAT group by trend (23% vs. 14%, p=0.087).Conclusion:While results may have partially been biased by differences in baseline characteristics, this current analysis disfavors the approach of AAT use for SSc-ILD.Disclosure of Interests:Michael Kreuter Grant/research support from: Roche, Boehringer, Consultant of: Roche, Boehringer, Speakers bureau: Boehringer, Roche, Francesco Bonella Grant/research support from: Boehringer, Consultant of: Boehringer, Roche, Bristol MS, Galapagos, Speakers bureau: Boehringer, Roche, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Ulf Müller-Ladner Speakers bureau: Biogen, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, Elise Siegert Grant/research support from: Actelion, Consultant of: AEC, Speakers bureau: NA, Claudia Guenther: None declared, Ina Koetter Grant/research support from: Novartis, Roche, Speakers bureau: Abbvie, Actelion, Celgene, MSD, UCB, Sanofi, Lilly, Pfizer, Novartis, Chugai, Roche, Boehringer, Norbert Blank Speakers bureau: Actelion, Roche, Boehringer, Pfizer, Chugai, Christiane Pfeiffer: None declared, Marc Schmalzing: None declared, Gabriele Zeidler: None declared, PETER KORSTEN Grant/research support from: Novartis, Juarms GmbH, Consultant of: Abbvie, Pfizer, Lilly, BMS, Speakers bureau: Abbvie, Pfizer, chugai, BMS, Lilly, Sanofi aventis, Laura Susok: None declared, Aaron Juche: None declared, Margitta Worm Consultant of: Mylan Gemany, Bencard Allergie, BBV Technologies S.A., Novartis, Biotest, Sanofi, Aimmune Therapies, Regeneron, Speakers bureau: ALK-Abello, Novartis, Sanofi, Biotest, Mylan, Actelion, HAL Allergie, Aimmune Bencard Allergie, Ilona Jandova: None declared, Jan Ehrchen: None declared, Cord Sunderkoetter: None declared, Gernot Keyszer: None declared, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Alexander Kreuter Speakers bureau: Sanofi, Abbvie, Merck Sharp&Dohme, Boehringer, Kathrin Kuhr: None declared, Hanns-Martin Lorenz Grant/research support from: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly. Scientific support and/or educational seminars and/or clinical studies: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, Thermo Fisher., Consultant of: see above, Pia Moinzadeh: None declared, Nicolas Hunzelmann Speakers bureau: Actelion, Boehringer

THU0330 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED ILD (SSC-ILD) AND DIFFERING EXTENTS OF SKIN FIBROSIS: FURTHER ANALYSES OF THE SENSCIS TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 395-396
Author(s):  
Y. Allanore ◽  
V. Steen ◽  
M. Kuwana ◽  
C. Denton ◽  
M. Matucci-Cerinic ◽  
...  
Keyword(s):  
Placebo Group ◽  
Systemic Sclerosis ◽  
Topoisomerase I ◽  
Statistical Testing ◽  
Skin Fibrosis ◽  
Annual Rate ◽  
Research Support ◽  
High Resolution Computed Tomography ◽  
Significant Difference ◽  
Rate Of Decline

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD compared with placebo, as shown by a significantly lower rate of decline in forced vital capacity (FVC) over 52 weeks. There was no significant difference between treatment groups in change in modified Rodnan skin score (mRSS) at week 52. An mRSS of 18–25 has been proposed as an upper cut-off to enrich a cohort for skin-progressive patients. Progression of skin fibrosis has been associated with later progression of ILD.Objectives:To assess the effects of nintedanib on the rate of FVC decline and change in mRSS in the SENSCIS trial in subgroups by mRSS <18 and ≥18 at baseline.Methods:Patients with SSc-ILD with onset of first non-Raynaud symptom <7 years before screening and ≥10% fibrosis of the lungs on a high-resolution computed tomography scan were randomised to receive nintedanib or placebo. We analysed the rate of decline in FVC (ml/year) over 52 weeks and the change from baseline in mRSS at week 52 in subgroups by mRSS (<18; ≥18) at baseline.Results:In the nintedanib and placebo groups, respectively, 219/288 (76.0%) and 226/288 (78.5%) patients had mRSS <18 at baseline. Compared with those with mRSS <18, patients with mRSS ≥18 had a lower mean FVC % predicted (68.3% vs 73.7%) and greater proportions were taking mycophenolate at baseline (58.1% vs 45.6%), were anti-topoisomerase I antibody positive (67.4% vs 58.7%) and had diffuse cutaneous SSc (100% vs 37.8%). The mean (SE) annual rate of decline in FVC in the placebo group was numerically greater in patients who had mRSS ≥18 than mRSS <18 at baseline (-131.7 [29.2] mL/year vs -81.4 [15.4] mL/year). The effect of nintedanib vs placebo on reducing the annual rate of decline in FVC was numerically more pronounced in patients with mRSS ≥18 (difference: 88.7 mL/year [95% CI 7.7, 169.8]) than mRSS <18 (difference: 26.4 mL/year (95% CI -16.8, 69.6) at baseline, but statistical testing did not indicate heterogeneity in the treatment effect of nintedanib between subgroups (p=0.18 for treatment-by-time-by-subgroup interaction) (Figure). In the nintedanib and placebo groups, respectively, changes in mRSS at week 52 were -2.2 (0.3) and -2.1 (0.3) (difference -0.1 [95% CI -1.0, 0.7]) in patients with mRSS <18 at baseline and -2.1 (0.7) and -1.6 (0.7) (difference -0.6 [95% CI -2.1, 1.0]) in patients with mRSS ≥18 at baseline (p=0.62 for treatment-by-visit-by-subgroup interaction).Conclusion:In the placebo group of the SENSCIS trial, the rate of decline in FVC over 52 weeks was numerically greater in patients with mRSS ≥18 than <18 at baseline, while reductions in mRSS were similar. A lower rate of FVC decline was observed in patients treated with nintedanib than placebo both in patients with mRSS ≥18 and <18 at baseline.Acknowledgments:The SENSCIS trial was funded by Boehringer IngelheimDisclosure of Interests:Yannick Allanore Grant/research support from: Yannick Allanore has received grants from Inventiva, Roche and Sanofi, Consultant of: Yannick Allanore has received fees from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Curzion, Inventiva, Roche, Sanofi, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Elizabeth Volkmann Grant/research support from: Forbius, Corbus Pharmaceuticals, Consultant of: Boehringer Ingelheim, Forbius, Speakers bureau: Boehringer Ingelheim, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB, Daniel Wachtlin Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, 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

scholarly journals OP0272 68GA-FAPI-04 PET/CT STUDY EXTENSION FOR THE ASSESSMENT OF FIBROBLAST ACTIVATION AND RISK EVALUATION IN SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 165.1-166
Author(s):  
C. Bergmann ◽  
J. H. W. Distler ◽  
C. Treutlein ◽  
K. Tascilar ◽  
A. T. Mueller ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Disease Progression ◽  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Control Group ◽  
Research Support ◽  
Fibroblast Activation ◽  
Pet Ct

Background:Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis (SSc). To date, the progression of SSc-ILD is judged by the accrual of lung damage on computed tomography (CT) and functional decline (forced vital capacity). However, this approach does not directly assess the activity of tissue remodeling. Moreover, prediction of the course of ILD in individual SSc patients remains challenging. Fibroblast Activation Protein (FAP) is a specific, ex vivo validated marker for activated fibroblasts.Objectives:The aims of this study were: 1. To assess differences in the uptake of 68GA-FAPI 04 in SSc-ILD patients compared to controls, to analyze 2. whether 68GA-FAPI 04 uptake at baseline correlates with other risk factors of disease progression and 3. Whether 68GA-FAPI 04 uptake is associated with the course of SSc-ILD.Methods:Between September 2018 and April 2020, 21 patients with SSc-ILD confirmed by HRCT and onset of SSc-ILD within ≤ 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET/CT imaging and standard-of-care procedures including HRCT and lung function testing (PFT) at baseline. Patients with SSc-ILD patients were followed-up for 6 months with HRCT and PFT. Follow-up 68Ga-FAPI-04 PET/CT scans were obtained in a subset of patients treated with nintedanib. We compared baseline 68Ga-FAPI-04 PET/CT uptake to standard diagnostic tools and currently used predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in FVC was analyzed using mixed-effects models.Results:68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in SSc-ILD compared to controls with a median (q1-q3 interval) wlSUVmean of 0.8 (0.6 to 2.1) in the SSc-ILD group and 0.5 (0.4 to 0.5) in the control group (p<0.0001 with Mann-Whitney test) and a median whole lung maximal standardized uptake value (wlSUVmax) of 4.4 (3.05 to 5.2) in the SSc-ILD group compared to 0.7 (0.65 to 0.7) in the control group (p<0.0001). wlFAPI-MAV and wlTL-FAPI were not measurable in control subjects, as no 68Ga-FAPI-04 uptake above background level was observed. In the SSc-ILD group the median wlFAPI-MAV was 254cm3 (163.4 to 442.3) and the median wlTL-FAPI was 183.6 cm3 (98.04 to 960.7). 68Ga-FAPI-04 uptake was higher in patients with extensive disease, with previous ILD progression or high EUSTAR activity scores. Increased 68Ga-FAPI-04 uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive 68Ga-FAPI-04-PET/CTs, changes in 68Ga-FAPI-04 uptake was concordant with the observed response to the fibroblast-targeting antifibrotic agent nintedanib.Conclusion:Our study presents first in human evidence that 68Ga-FAPI-04-fibroblast uptake correlates with fibrotic activity and disease progression in the lungs of SSc-ILD patients and that 68Ga-FAPI-04-PET/CT may be of potential to improve risk assessment of SSc-ILD.Figure 1.A and B:68Ga-FAPI-04 PET/CT scan from a patient with SSc-ILD with selective 68Ga-FAPI-04 uptake in fibrotic areas of the left- and right lower lung lobes (red arrows), but not in non-fibrotic areas such as the middle lobe (green arrow). B Corresponding CT component.Acknowledgements:We gratefully acknowledge Prof. Uwe Haberkorn (University Hospital Heidelberg and DKFZ, Heidelberg, Germany) and iTheranostics Inc. (Dulles, VA, USA) for providing the precursor FAPI-04.Disclosure of Interests:Christina Bergmann: None declared, Jörg H.W. Distler Speakers bureau: Actelion, Anamar, ARXX, Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Christoph Treutlein: None declared, Koray Tascilar Speakers bureau: Gilead sciences GmbH, Pfizer Turkey, UCB Turkey, Anna-Theresa Mueller: None declared, Armin Atzinger: None declared, Alexandru-Emil Matei: None declared, Johannes Knitza: None declared, Andrea-Hermina Györfi: None declared, Anja Lueck: None declared, Clara Dees: None declared, Alina Soare: None declared, Andreas Ramming: None declared, Verena Schönau: None declared, Oliver Distler Speakers bureau: Arxx Therapeutics, Baecon Discovery, Blade Therapeutics,Bayer, Böhringer Ingelheim, Catenion,Competitive Drug Development International Ltd, Corbuspharma, CSL Behring, ChemomAb, Horizon Pharmaceuticals, Ergonex, Galaapagos NV, Glenmark Pharmaceuticals,GSK, Inventiva, Italfarmaco, IQvia, Kymera, Lilly, Medac, Medscape, MSD, Novartis, Pfizer, Roche, Sanofi, Taget Bio Sciencec, UCB, Grant/research support from: Bayer,Böhringer Ingelheim, Mitsubishi Tanabe Pharma, Olaf Prante: None declared, Philipp Ritt: None declared, Theresa Ida Goetz: None declared, Markus Koehner: None declared, Michael Cordes: None declared, Tobias Baeuerle: None declared, Torsten Kuwert Speakers bureau: Honoraria for occasional lectures by Siemens Healthineers, Grant/research support from: Research grant to the Clinic of Nuclear Medicine by this entity covering projects in the field of SPECT/CT, Georg Schett: None declared, Christian Schmidkonz: None declared

Does anti-acid treatment influence disease progression in SSc-ILD? Data form the German SSc-network

2020 ◽  
Author(s):  
M Kreuter ◽  
F Bonella ◽  
N Blank ◽  
E Siegert ◽  
J Henes ◽  
...  
Keyword(s):  
Disease Progression ◽  
Acid Treatment ◽  
Data Form

scholarly journals Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Andréa Tavares Dantas ◽  
Sayonara Maria Calado Gonçalves ◽  
Anderson Rodrigues de Almeida ◽  
Rafaela Silva Guimarães Gonçalves ◽  
Maria Clara Pinheiro Duarte Sampaio ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Vascular Involvement ◽  
Digital Ulcers ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Significant Difference ◽  
Skin Biopsies

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

scholarly journals AB0566 NAILFOLD EXTENT OF REDUCED CAPILLARY DENSITY IS ASSOCIATED WITH DIGITAL ULCERS AND WITH AN INCREASED RISK OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1580.2-1580
Author(s):  
R. De Angelis ◽  
F. Salaffi
Keyword(s):  
Systemic Sclerosis ◽  
Laboratory Data ◽  
Quantitative Measure ◽  
Capillary Density ◽  
Optical Probe ◽  
Typical Feature ◽  
Slight Reduction ◽  
Digital Ulcers ◽  
Increased Risk ◽  
Significant Difference

Background:A growing evidence supports the role of microvasculopathy as a primary pathogenic event in systemic sclerosis (SSc). The most commonly used imaging technique to identify microangiopathy in SSc is high magnification videocapillaroscopy (NVC), and reduced capillary density and/or capillary loss, which is a typical feature of “scleroderma microangiopathy”, easily identified by NVC, has been associated with digital ulcers (DUs). Different approaches have been proposed to measure capillary density or capillary loss. Some of these were qualitative methods, others semi-quantitative, others only concerned a limited nailfold area, without ever evaluating the overall density, which is more suitable for quantitative estimate.Objectives:To assess the association between the extent of different values of nailfold capillary density and the presence of DUs and to identify the risk of developing DUs, based on quantitative parameters.Methods:The study involved 54 SSc selected patients (47 women and 7 men, mean age 59.5 years, 50 with limited and 4 with diffuse). The study population came from an ongoing database, that includes clinical and laboratory data of patients with definite SSc. A videocapillaroscope (VideoCap® 3.0, DS Medica, Milan, Italy) with a 200x optical probe was used. During examination, eight fingers (fingers 2–5 of each hand), 4 fields per finger, according to the standard literature were assessed. For each patient, a total of 32 images were collected, then classified as having either “normal”, “non-specific” or the “scleroderma pattern” (SP). Capillary density was defined as the number of capillaries/mm in the distal row, regardless of its shape and morphology. Avascular areas were defined by the absence of loops within a width/area extending over more than 500 microns. For each patient, the SP images were further graded with no/slight reduction of the capillary density (7-9 loops/mm) (NOR), with a well-defined reduction of capillary density (6-4 loops/mm) (RED) and with loss of capillaries (<4) plus avascular areas (AA). Then, the overall percentages were calculated (the number with SP, the number with NOR, with RED and with AA, respect to 32), thus obtaining the quantitative measures. All data were analysed using the MedCalc® version 18.6; 64-bit (MedCalc Software, Mariakerke, Belgium).Results:A total of 1728 images were analyzed. Patients with DUs were 16/54 (29.6%). All patients had a SP, but only five patients showed a SP along the entire nailfold. A comparison between patients with or without DUs showed a significant difference both for the overall extent of AA (p=0.032), and particularly for the overall extent of RED (p<0.001). No significant difference was found regarding the overall extent of the SP (p=0.085). Factor significantly associated with DUs in multivariate analysis was the overall extent of RED (p=0.0286). The ROC curve was very effective at discriminating the capillary feature able to distinguish patients with DUs from patients without DUs. The discriminatory power of the overall extent of RED was very good, with an AUC of 0.948 (95 % CI 0.852 ± 0.990). Then, we calculated the cut-off values of the overall extent of RED for presence/absence of DUs with the highest combination of sensitivity and specificity. The resulting cut-off value (Yourden index of 0.825) was >68.7 (sensitivity 92.31 %; specificity 90.24 %) with a LR+ of 9.46.Conclusion:Our data strongly support that the capillary density between 4 and 6 loops/mm is the best capillaroscopic quantitative measure associated with DUs and able to discriminate the probability of having DUs. If all SSc-specific antibodies and/or other laboratory/clinical parameters are not yet available, the overall capillary density can allow physicians to assess SSc patients easily, regarding DUs and risk for developing DUs.Disclosure of Interests:None declared

scholarly journals New risk model is able to identify patients with a low risk of progression in systemic sclerosis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001524
Author(s):  
Nina Marijn van Leeuwen ◽  
Marc Maurits ◽  
Sophie Liem ◽  
Jacopo Ciaffi ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
High Risk ◽  
Disease Progression ◽  
Risk Model ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Expert Assessment ◽  
Risk Of Progression

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

scholarly journals Risk of COVID-19 Infection Among Chronic Rhinosinusitis Patients Receiving Oral Corticosteroids

2021 ◽  
pp. 019459982110069
Author(s):  
Lauren E. Miller ◽  
Neil Bhattacharyya
Keyword(s):  
Conservative Treatment ◽  
Chronic Rhinosinusitis ◽  
Treatment Regimen ◽  
Medical Management ◽  
Steroid Use ◽  
Positive Diagnosis ◽  
Increased Risk ◽  
Significant Difference ◽  
Oral Corticosteroids

Chronic rhinosinusitis (CRS) management frequently comprises conservative treatment, including a combination of topical and oral corticosteroids (OCSs). However, in the midst of the coronavirus disease 2019 (COVID-19) pandemic, providers may have been reluctant to prescribe OCSs out of possible concern for an increased risk of contracting COVID-19 or developing more severe COVID-19 symptoms. This study thus sought to explore the association between the use of OCSs and the development of COVID-19 in patients with CRS. We found no statistically significant difference in the rates of patients with a positive diagnosis of COVID-19 who underwent an OCS treatment regimen compared to those who did not, both within 28 days ( P = .389) and 14 days ( P = .676) prior to the COVID-19 test. Given OCSs are often a major component of medical management of CRS, this study proves helpful in counseling patients on risks of steroid use in CRS treatment during the COVID-19 pandemic.

scholarly journals AB0132 THE STUDY OF SUBCLINICAL SYNOVITIS DETECTED BY ULTRASONOGRAPHY AND MRI IN RA PATIENTS AFTER REACHING CLINICAL REMISSION ON PATIENT’S SUBJECTIVE SYMPTOMS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1094.2-1094
Author(s):  
M. Nawata ◽  
K. Someya ◽  
T. Aritomi ◽  
M. Funada ◽  
K. Nakamura ◽  
...  
Keyword(s):  
Clinical Remission ◽  
Research Funding ◽  
Morning Stiffness ◽  
Univariate Analysis ◽  
P Value ◽  
Research Support ◽  
Residual Symptoms ◽  
Logistic Analysis ◽  
Significant Difference ◽  
Multivariate Logistic Analysis

Background:The goal of treatment in rheumatoid arthritis (RA) is to achieve remission. There is the patient with residual symptoms in the Japanese RA patient who achieved clinical remission. There are not many studies to examine the relation between everyday life, social activity and evaluation of disease activities using high-sensitivity image examinations (musculoskeletal ultrasound (MSKUS) and MRI).Objectives:To examine the relationship between subjective residual symptoms and imaging examinations in RA patients who have achieved clinical remission.Methods:30 RA patients who achieved SDAI remission during RA treatment. Age, sex, disease duration, physical findings, serological markers, disease activity, HAQ, EQ-5D-5L, FACIT-F, Patient Reported Outcomes (PROs), EGA and medications were evaluated. 44 joints were assessed by MSKUS with gray scale (GS) and power doppler (PD) and contrast-enhanced bilateral joint MRI scoring with OMERACT-RAMRIS scoring.Results:1. The mean SDAI of the 30 RA patients was 1.3. 2.In the analysis of the presence or absence of subjective residual symptoms that led to remission of SDAI (Table 1).Table 1.Subjective residual symptoms/presence (N=17)Subjective residual symptoms/absence (N=13)Univariate analysisp valueMultivariate logistic analysisp valueTJC0.0±0.00.3±0.50.0173HAQ0.4±0.40.05±0.10.00950.00181EQ5D-5L0.8±0.10.9±0.00.0001FACIT-F14.5±9.84.6±4.30.0233Morning stiffness (min)256.5±564.80.0±0.00.0210Pain (VAS) (mm)9.2±9.50.9±1.50.00440.0455PGA (mm)7.7±9.00.5±1.10.0013(1). In the univariate analysis, the number of tender joints, HAQ, EQ-5D-5L, FACIT-F, morning stiffness, and pain VAS were extracted with significant differences.(2). In multivariate logistic analysis, HAQ and pain VAS were extracted as independent factors with significant differences. 3.In univariate analysis of the association between HAQ and pain VAS extracted in multivariate logistic analysis and imaging examinations (MSKUS/MRI), MRI-synovitis was extracted with a significant difference in HAQ.Conclusion:1. It was suggested that Pain VAS and HAQ due to RA could be identified in patients reaching SDAI remission. 2. In patients reaching SDAI remission, Pain VAS ≤10 or HAQ ≤0.5 suggested that subjective residual symptoms may be eliminated. 3. HAQ ≤ 0.5 suggests that synovitis is less likely to be detected on MRI. 4. In patients who have reached SDAI remission, little residual inflammation was observed on US, suggesting that induction of remission is important not only to prevent joint destruction, but also to improve and maintain long-term QoL.Disclosure of Interests:MASAO NAWATA Grant/research support from: I have received research funding from Eli Lilly Japan K.K., Kazuki Someya: None declared, Takafumi Aritomi: None declared, Masashi funada: None declared, Katsumi Nakamura: None declared, SAITO KAZUYOSHI Grant/research support from: I have received research funding from Eli Lilly Japan K.K., Yoshiya Tanaka Speakers bureau: I have received speaking fees from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen, Consultant of: I have received consulting fees from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, Bristol-Myers, Astellas, Eisai, Janssen, Pfizer, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, and Santen, Grant/research support from: I have received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, and Bristol-Myers

scholarly journals THU0351 MUSCLE INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTI-PM/SCL+ ANTIBODIES IS ASSOCIATED WITH CARDIAC AND PULMONARY INVOLVEMENT. ANALYSIS OF THE MULTICENTRE EUSTAR COHORT.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 407.1-407
Author(s):  
M. G. Lazzaroni ◽  
S. Zingarelli ◽  
P. Airò ◽  
Y. Allanore ◽  
O. Distler
Keyword(s):  
Systemic Sclerosis ◽  
Cardiac Involvement ◽  
Severe Disease ◽  
Disease Onset ◽  
Pulmonary Involvement ◽  
Left Ventricular ◽  
Research Support ◽  
Muscle Involvement ◽  
Group A ◽  
Tendon Friction Rubs

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, 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

scholarly journals AB0436 OUTCOMES OF DOSE-REDUCTION OR DISCONTINUATION OF TOCILIZUMAB IN PATIENTS WITH EARLY DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1246.3-1247
Author(s):  
Y. Isomura ◽  
Y. Yamasaki ◽  
Y. Shirai ◽  
M. Kuwana
Keyword(s):  
Systemic Sclerosis ◽  
Dose Reduction ◽  
Clinical Outcomes ◽  
Inflammatory Markers ◽  
Topoisomerase I ◽  
Phase Iii ◽  
Optimal Timing ◽  
Skin Thickness ◽  
Research Support ◽  
Diffuse Cutaneous Systemic Sclerosis

Background:Potential efficacy and favorable safety profiles of tocilizumab (TCZ) have been demonstrated in patients with diffuse cutaneous systemic sclerosis (dcSSc) [1, 2]. However, clinical outcomes after dose-reduction or discontinuation of TCZ due to an improvement of skin thickness remain unclear.Objectives:To investigate the clinical outcomes after dose-reduction or discontinuation of TCZ in patients with dcSSc in a real-world setting.Methods:This is a single-center, retrospective, observational study using a database of consecutive SSc patients who visited our center between April 2014 and October 2020. For this study, we selected eligible patients from the database based on the following criteria: patients who (i) fulfilled the ACR/EULAR classification criteria, (ii) were classified as having dcSSc, (iii) had been treated with TCZ for at least 6 months, and (iv) were follow-up >6 months after TCZ introduction. Clinical information including demographic and clinical characteristics at TCZ introduction; dosing, administration route, and adherence of TCZ; and serial clinical parameters (modified Rondan total skin thickness score [mRSS], and percent predicted forced vital capacity [%FVC]), safety profiles, and outcomes after TCZ introduction regardless of TCZ continuation were extracted from the database.Results:Of 404 patients enrolled in the database, 13 dcSSc patients were eligible for this study. Baseline characteristics included a mean age of 51 ± 9 years, 85% female, disease duration of 27 ± 24 months, and mRSS of 19.5 ± 10.6. Seven patients (54%) had HRCT-confirmed ILD at baseline, and 9 (69%) were positive for anti-topoisomerase I antibody. Two (14%) and 11 (85%) were on mycophenolate mofetil and low-dose prednisolone (7.2 ± 6.0 mg/day), respectively. Seven patients (54%) each had active skin disease and elevated inflammatory markers defined in the phase III clinical trial [2], while only 4 (31%) fulfilled the inclusion criteria. TCZ was initially administered intravenously (8 mg/kg every 4 weeks) in 8 patients and subcutaneously in 5 (162 mg every 2 weeks in 4 and every week in one). At one year, mRSS was improved from 20.9 ± 11.4 to 10.7 ± 8.9 in 11 patients (p = 0.007), and %FVC was stable in 7 patients with ILD (76.8 ± 15.0 to 78.6 ± 16.1). During the observation period of 60.4 ± 26.7 months, 4 patients were treated with a stable dose of TCZ, while TCZ dose was reduced and/or discontinued in 9. Four of them discontinued TCZ due to adverse events (n = 2; acute lung injury and phlegmon) or prominent improvement of skin thickening (n = 2). Of 9 patients with dose reduction/discontinuation of TCZ, 4 patients who discontinued TCZ (n = 3) or received dose reduction of TCZ (n = 1) experienced a recurrence of progressive skin thickening together with inflammatory complications, including edematous induration of the skin, progression of ILD, polyarthritis, and/or pericarditis with increased inflammatory markers. The interval between dose-reduction/discontinuation of TCZ and clinical worsening ranged from 2 to 11 months. These manifestations were promptly improved by dose-escalation or resumption of TCZ in all patients except one who experienced progressive ILD and died of respiratory failure 27 months later.Conclusion:In dcSSc patients who experienced improvement of skin thickness during treatment with TCZ, dose-reduction or discontinuation of TCZ may result in a recurrence of the disease. Randomized comparative studies are necessary to examine optimal timing for dose-reduction or discontinuation of TCZ in dcSSc patients after improvement of skin thickness.References:[1]Khanna, D., et al., Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis, 2018. 77(2):212-220.[2]Khanna, D., et al., Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med, 2020; 8(10): 963-974.Disclosure of Interests:Yohei Isomura: None declared, Yoshioki Yamasaki Speakers bureau: Boehringer-Ingelheim, Nippon Shinyaku, Bristol Myers, Yuichiro Shirai Speakers bureau: Janssen, Grant/research support from: Janssen, Masataka Kuwana Speakers bureau: Abbie, Astellas, Asahi Kasei Parma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, MBL, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Tanabe-Mitsubishi, Consultant of: Boehringer-Ingelheim, Chugai, Corbus, MBL, Mochida, Grant/research support from: Boehringer-Ingelheim, Chugai, Eisai, MBL, Ono Pharmaceuticals, Tanabe-Mitsubishi

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