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2. Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial

Author

Denton, CP, Goh, NS, Humphries, SM, Maher, TM, Spiera, R, Devaraj, A, Ho, L, Stock, C, Erhardt, E, Alves, M, Wells, AU, and SENSCIS trial investigators

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Objective To assess associations between the extent of fibrotic interstitial lung disease (ILD) and forced vital capacity (FVC) at baseline and change in FVC over 52 weeks in patients with systemic sclerosis-associated ILD (SSc-ILD) in the SENSCIS trial. Material and methods We used generalized additive models, which involve few assumptions and allow for interaction between non-linear effects, to assess associations between the extent of fibrotic ILD on high-resolution computed tomography (HRCT), and the interplay of extent of fibrotic ILD on HRCT and FVC % predicted, at baseline and FVC decline over 52 weeks. Results In the placebo group (n = 288), there was weak evidence of a modest association between a greater extent of fibrotic ILD at baseline and a greater decline in FVC % predicted at week 52 [r: –0.09 (95% CI –0.2, 0.03)]. Higher values of both the extent of fibrotic ILD and FVC % predicted at baseline tended to be associated with greater decline in FVC % predicted at week 52. In the nintedanib group (n = 288), there was no evidence of an association between the extent of fibrotic ILD at baseline and decline in FVC % predicted at week 52 [r: 0.01 (95% CI: -0.11, 0.12)] or between the interplay of extent of fibrotic ILD and FVC % predicted at baseline and decline in FVC % predicted at week 52. Conclusions Data from the SENSCIS trial suggest that patients with SSc-ILD are at risk of ILD progression and benefit from nintedanib largely irrespective of their extent of fibrotic ILD at baseline. Study registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02597933.

Published
2022

3. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

Author

Distler, O, Highland, Kb, Gahlemann, M, Azuma, A, Fischer, A, Mayes, Md, Raghu, G, Sauter, W, Girard, M, Alves, M, Clerisme-Beaty, E, Stowasser, S, Tetzlaff, K, Kuwana, M, Maher, Tm, Bergna, M, Casado, G, Mannucci Walter, P, Proudman, S, Stevens, W, Thakkar, V, Troy, L, Loeffler-Ragg, J, Olschewski, H, Bondue, B, Houssiau, F, Smith, V, Wuyts, W, Johnson, S, Keystone, E, Khalidi, N, Levesque, M, Maturana Rozas, R, Silva Orellana, A, Huang, C, Li, J, Jiang, Z, Liu, Y, Xiao, W, Xu, J, Zeng, X, Zheng, Y, Zou, H, Becvar, R, Madsen, H, Søndergaard, K, Kilpeläinen, M, Myllärniemi, M, Agard, C, Allanore, Y, Bourdin, A, Cottin, V, Crestani, B, Diot, E, Dominique, S, Hachulla, E, Jouneau, S, Leroy, S, Nunes, H, Prevot, G, Wallaert, B, Wemeau, L, Aringer, M, Bewig, B, Blaas, S, Distler, J, Ehrchen, J, Ewert, R, Gläser, S, Henes, J, Hunzelmann, N, König, R, Kötter, I, Kreuter, M, Prasse, A, Schulze-Koops, H, Sfikakis, P, Vlachoyiannopoulos, P, Losonczy, G, Behera, D, Gayathri Devi HJ, Kadel, J, Kawedia, M, Kumar, D, Kumar, U, Lokhande, R, Malpani, A, Mohan, M, Nalawade, A, Parakh, U, Swarnakar, R, Shobha, V, Thangakunam, B, Udwadia, Z, Henry, M, O'Reilly, K, Balbir-Gurman, A, Kramer, M, Litinsky, I, Rosner, I, Cutolo, M, Gabrielli, A, Iaccarino, L, Pesci, A, Riccieri, V, Vettori, S, Funakubo, Y, Inoue, Y, Kawakami, A, Kawaguchi, Y, Kawamura, T, Kondoh, Y, Nanki, T, Nishioka, Y, Nozawa, K, Oguragawa, T, Okamoto, M, Sano, H, Sasai, R, Sasaki, N, Suda, T, Takahashi, H, Takeuchi, T, Tanaka, S, Yamasaki, Y, Ch'Ng, Ss, Cheah, C, Kan, S, Raja Mohamed RB, Selman, M, de Vries-Bouwstra JK, van den Toorn, L, Vonken, M, Voskuyl, Ae, Hoffmann-Vold, Am, Seip, M, Dankiewicz-Fares, I, Olesiejuk, R, Pulka, G, Szepietowski, J, Alves, J, Bernardes, M, Cordeiro, A, Costa, J, Neves, S, Salvador, Mj, Alegre Sancho, J, Carreira Delgado, P, Castellví Barranco, I, Cifrián Martínez, J, Guillén Del Castillo, A, Ovalles, Jg, López-Longo, Fj, Rivera Gallego, A, Freire Dapena MC, Román Ivorra JA, Ekwall, Ah, Maurer, B, Mihai, Cm, Müller, R, Mahakkanukrauh, A, Nantiruj, K, Siripaitoon, B, Denton, Cp, Herrick, A, Madhok, R, West, A, Bascom, R, Criner, G, Csuka, Me, Dematte D'Amico, J, Ettinger, N, Gerbino, A, Gerke, A, Glassberg, M, Glazer, C, Golden, J, Gripaldo, R, Gupta, N, Hamblin, M, Highland, K, Ho, L, Huggins, Jt, Hummers, L, Jones, L, Kahaleh, M, Khanna, D, Kim, H, Lancaster, Lh, Luckhardt, T, Mayes, M, Mendoza Ballesteros, F, Mooney, J, Mohabir, P, Morrissey, B, Moua, T, Padilla, M, Patel, N, Perez, R, Roman, J, Rossman, M, Russell, T, Saketkoo, L, Shah, A, Shlobin, O, Scholand, Mb, Simmssetts, R, Spiera, R, Steen, V, Veeraraghavan, S, Weigt, S., Distler, O, Highland, Kb, Gahlemann, M, Azuma, A, Fischer, A, Mayes, Md, Raghu, G, Sauter, W, Girard, M, Alves, M, Clerisme-Beaty, E, Stowasser, S, Tetzlaff, K, Kuwana, M, Maher, Tm, SENSCIS Trial Investigators., Bergna M, Casado, G, Mannucci Walter, P, Proudman, S, Stevens, W, Thakkar, V, Troy, L, Loeffler-Ragg, J, Olschewski, H, Bondue, B, Houssiau, F, Smith, V, Wuyts, W, Johnson, S, Keystone, E, Khalidi, N, Levesque, M, Maturana Rozas, R, Silva Orellana, A, Huang, C, Li, J, Jiang, Z, Liu, Y, Xiao, W, Xu, J, Zeng, X, Zheng, Y, Zou, H, Becvar, R, Madsen, H, Søndergaard, K, Kilpeläinen, M, Myllärniemi, M, Agard, C, Allanore, Y, Bourdin, A, Cottin, V, Crestani, B, Diot, E, Dominique, S, Hachulla, E, Jouneau, S, Leroy, S, Nunes, H, Prevot, G, Wallaert, B, Wemeau, L, Aringer, M, Bewig, B, Blaas, S, Distler, J, Ehrchen, J, Ewert, R, Gläser, S, Henes, J, Hunzelmann, N, König, R, Kötter, I, Kreuter, M, Prasse, A, Schulze-Koops, H, Sfikakis, P, Vlachoyiannopoulos, P, Losonczy, G, Behera, D, Gayathri Devi, Hj, Kadel, J, Kawedia, M, Kumar, D, Kumar, U, Lokhande, R, Malpani, A, Mohan, M, Nalawade, A, Parakh, U, Swarnakar, R, Shobha, V, Thangakunam, B, Udwadia, Z, Henry, M, O'Reilly, K, Balbir-Gurman, A, Kramer, M, Litinsky, I, Rosner, I, Cutolo, M, Gabrielli, A, Iaccarino, Laura, Pesci, A, Riccieri, V, Vettori, S, Funakubo, Y, Inoue, Y, Kawakami, A, Kawaguchi, Y, Kawamura, T, Kondoh, Y, Nanki, T, Nishioka, Y, Nozawa, K, Oguragawa, T, Okamoto, M, Sano, H, Sasai, R, Sasaki, N, Suda, T, Takahashi, H, Takeuchi, T, Tanaka, S, Yamasaki, Y, Ch'Ng, S, Cheah, C, Kan, S, Raja Mohamed, Rb, Selman, M, de Vries-Bouwstra, Jk, van den Toorn, L, Vonken, M, Voskuyl, Ae, Hoffmann-Vold, Am, Seip, M, Dankiewicz-Fares, I, Olesiejuk, R, Pulka, G, Szepietowski, J, Alves, J, Bernardes, M, Cordeiro, A, Costa, J, Neves, S, Salvador, Mj, Alegre Sancho, J, Carreira Delgado, P, Castellví Barranco, I, Cifrián Martínez, J, Guillén Del Castillo, A, Ovalles, Jg, López-Longo, Fj, Rivera Gallego, A, Freire Dapena, Mc, Román Ivorra, Ja, Ekwall, Ah, Maurer, B, Mihai, Cm, Müller, R, Mahakkanukrauh, A, Nantiruj, K, Siripaitoon, B, Denton, Cp, Herrick, A, Madhok, R, West, A, Bascom, R, Criner, G, Csuka, Me, Dematte D'Amico, J, Ettinger, N, Gerbino, A, Gerke, A, Glassberg, M, Glazer, C, Golden, J, Gripaldo, R, Gupta, N, Hamblin, M, Highland, K, Ho, L, Huggins, Jt, Hummers, L, Jones, L, Kahaleh, M, Khanna, D, Kim, H, Lancaster, Lh, Luckhardt, T, Mayes, M, Mendoza Ballesteros, F, Mooney, J, Mohabir, P, Morrissey, B, Moua, T, Padilla, M, Patel, N, Perez, R, Roman, J, Rossman, M, Russell, T, Saketkoo, L, Shah, A, Shlobin, O, Scholand, Mb, Simmssetts, R, Spiera, R, Steen, V, Veeraraghavan, S, Weigt, S., National Institute for Health Research, British Lung Foundation, University of Zurich, and Distler, Oliver

Subjects
Male, Vital capacity, Indoles, Vital Capacity, Administration, Oral, 2700 General Medicine, 030204 cardiovascular system & hematology, Pulmonary function testing, law.invention, oral, Idiopathic pulmonary fibrosis, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, SENSCIS Trial Investigators, CYCLOPHOSPHAMIDE, Clinical endpoint, scleroderma, 030212 general & internal medicine, Enzyme Inhibitors, 11 Medical and Health Sciences, lung diseases, Lung Diseases, Interstitial -- drug therapy -- etiology -- physiopathology, 10051 Rheumatology Clinic and Institute of Physical Medicine, General Medicine, respiratory system, Sciences bio-médicales et agricoles, Middle Aged, Protein-Tyrosine Kinases, MANIFESTATIONS, Disease Progression, Nintedanib, Female, TYROSINE KINASE INHIBITOR, Life Sciences & Biomedicine, CLINICAL-TRIALS, Adult, Diarrhea, medicine.medical_specialty, FIBROBLASTS, 610 Medicine & health, Placebo, administration, behavioral disciplines and activities, 03 medical and health sciences, FEV1/FVC ratio, Medicine, General & Internal, Double-Blind Method, Internal medicine, General & Internal Medicine, Enzyme Inhibitors -- adverse effects -- therapeutic use, SCORE, medicine, Humans, Indoles -- adverse effects -- therapeutic use, Scleroderma, Systemic -- complications -- drug therapy, Science & Technology, Scleroderma, Systemic, Protein-Tyrosine Kinases -- antagonists & inhibitors, business.industry, MORTALITY, interstitial, PULMONARY-FUNCTION, systemic, STANDARDIZATION, medicine.disease, EFFICACY, respiratory tract diseases, body regions, chemistry, adult, diarrhea, disease progression, double-blind method, enzyme inhibitors, female, humans, indoles, lung diseases, interstitial, male, middle aged, protein-tyrosine kinases, scleroderma, systemic, vital capacity, business, Lung Diseases, Interstitial, Diarrhea -- chemically induced
Abstract

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD., info:eu-repo/semantics/published

Published
2019

4. Digital ulcers: should debridement be a standard of care in systemic sclerosis?

Author

Hughes, M, Alcacer-Pitarch, B, Allanore, Y, Baron, M, Boin, F, Bruni, C, Chung, L, Del Galdo, F, Denton, CP, and Matucci-Cerinic, M

Subjects
integumentary system
Abstract

Digital ulcers are a serious, recurrent complication in patients with systemic sclerosis. They are often slow to heal and exquisitely painful. Local wound care, such as debridement of the wound bed, is an essential component in the management of digital ulcers in systemic sclerosis. However, digital ulcer debridement is not a standard of care, and there is substantial international variation in the use of this approach. In this Viewpoint, we discuss the assessment of the wound bed and different methods of debridement using the model of tissue management, infection and inflammation, moisture control, and wound edge or epidermal advancement, known as TIME. We highlight the challenges in standard practice and the need for research into local wound care for this type of ulceration, before suggesting a potential roadmap to develop a standardised approach to support ulcer debridement in systemic sclerosis. Debridement might be the missing component in optimising the management of digital ulcers and we propose that the approach should be rigorously investigated as a standard of care in this common complication of systemic sclerosis.

Published
2020

5. Proposal of outcome measures to be used on a 12-month open label drug trial in Juvenile Systemic Sclerosis. Results of the 3rd Consensus Meeting in Hamburg December 2018

Author

Foeldvari, I, Torok, K, Ambartsumyan, L, Anton, J, Beyer, C, Blakley, M, Constantin, T, Costa Reis, P, Curran, M, Cutolo, M, del Gado, F, Denton, CP, Fligelstone, K, Hinrichs, B, Höger, A, Ingegnoli, F, Kasapcopur, O, Li, S, Nemcova, D, Orteu, C, Pilkington, C, Smith, V, Stevens, A, Stevens, B, Zhen, A, Khanna, D, and Furst, D

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Juvenile systemic sclerosis (jSSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed. To develop an open label drug trial for the treatment of jSSc patients, it is necessary to clearly define how to evaluate outcomes in this disease,[for full text, please go to the a.m. URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Published
2019
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6. Early treatment with Ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA-Study)

Author

Xanthouli, P, Pan, Z, Marra, A, Benjamin, N, Eichstaedt, C, Blank, N, Bossone, E, Cittadini, A, Coghlan, G, Denton, CP, Distler, O, Egenlauf, B, Fischer, C, Harutyunova, S, Lorenz, HM, and Grünig, E

Subjects
ddc: 610, integumentary system, 610 Medical sciences, Medicine, skin and connective tissue diseases
Abstract

Background: The objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated mPAP. Methods: Thirty-eight SSc-patients with mildly[for full text, please go to the a.m. URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Published
2019
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7. S69 Verification of genetic associations with scleroderma associated interstitial lung disease

Author

Stock, CJW, primary, DeLauretis, A, additional, Visca, D, additional, Daccord, C, additional, Kokosi, M, additional, Kouranos, V, additional, Margaritopoulos, G, additional, George, PM, additional, Molyneaux, PL, additional, Chua, F, additional, Maher, TM, additional, Abraham, DJ, additional, Denton, CP, additional, Ong, V, additional, Wells, AU, additional, and Renzoni, EA, additional

Published
2019
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8. S86 Serum biomarkers in SSc-ILD: association with presence, severity and prognosis

Author

Stock, CJW, primary, Visca, D, additional, DeLauretis, A, additional, Daccord, C, additional, Kokosi, M, additional, Alfieri, V, additional, Kouranos, V, additional, Margaritopoulos, G, additional, George, PM, additional, Molyneaux, PL, additional, Chua, F, additional, Maher, TM, additional, Ong, V, additional, Abraham, DJ, additional, Denton, CP, additional, Wells, AU, additional, and Renzoni, EA, additional

Published
2019
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9. Smoking in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study

Author

Jaeger, VK, Valentini, G, Hachulla, E, Cozzi, F, Distler, O, Airó, P, Czirják, L, Allanore, Y, Siegert, E, Rosato, E, Matucci-Cerinic, M, Caimmi, C, Henes, J, Carreira, PE, Smith, V, del Galdo, F, Denton, CP, Ullman, S, Langhe, ED, Riccieri, V, Alegre-Sancho, JJ, Rednic, S, Müller-Ladner, U, Walker, UA, and EUSTAR coauthors

Subjects
smoking, systemic sclerosis, scleroderma, respiratory tract diseases
Abstract

OBJECTIVE: Data on the role of tobacco exposure in systemic sclerosis (SSc ; scleroderma) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations, based on the European Scleroderma Trials and Research group database. METHODS: Adult SSc patients with data on smoking history and a 12-24-month follow-up visit were included. Associations of severity and progression of organ involvement with smoking history and the Comprehensive Smoking Index were assessed using multivariable regression analyses. RESULTS: A total of 3, 319 patients were included (mean age 57 years, 85% female) ; 66% were never smokers, 23% were ex-smokers, and 11% were current smokers. Current smokers had a lower percentage of antitopoisomerase autoantibodies than previous or never smokers (31% versus 40% and 45%, respectively). Never smokers had a higher baseline forced expiratory volume in 1 second/forced vital capacity (FEV1 /FVC) ratio than previous and current smokers (P < 0.001). The FEV1 /FVC ratio declined faster in current smokers than in never smokers (P = 0.05) or ex-smokers (P = 0.01). The baseline modified Rodnan skin thickness score (MRSS) and the MRSS decline were comparable across smoking groups. Although heavy smoking (>25 pack- years) increased the odds of digital ulcers by almost 50%, there was no robust adverse association of smoking with digital ulcer development. CONCLUSION: The known adverse effect of smoking on bronchial airways and alveoli is also observed in SSc patients ; however, robust adverse effects of smoking on the progression of SSc-specific pulmonary or cutaneous manifestations were not observed.

Published
2018

10. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach

Author

Mukerjee, D, St George, D, Coleiro, B, Knight, C, Denton, CP, Davar, J, Black, CM, and Coghlan, JG

Subjects
Medical research -- Analysis -- Physiological aspects -- Health aspects, Medicine, Experimental -- Analysis -- Physiological aspects -- Health aspects, Patients -- Care and treatment -- Health aspects -- Physiological aspects -- Research -- Analysis, Mortality -- Health aspects -- Causes of -- Prevention -- Prognosis -- Malta -- United Kingdom, Rheumatic diseases -- Health aspects -- Research -- Care and treatment -- Prevention -- Prognosis -- Complications and side effects, Sclerosis -- Health aspects -- Prevention -- Complications and side effects -- Prognosis -- Research -- Care and treatment, Pulmonary artery -- Health aspects -- Physiological aspects -- Research -- Analysis, Cookery -- Health aspects -- Causes of -- Care and treatment -- Research -- Physiological aspects -- Analysis, Hypertension -- Health aspects -- Causes of -- Care and treatment -- Prognosis -- Research -- Complications and side effects -- Prevention, Health
Abstract

Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. Methods: A prospective four year [...]

Published
2003

11. Non-invasive measurement of biomechanical skin properties in systemic sclerosis. (Extended Report)

Author

Balbir-Gurman, A, Denton, CP, Nichols, B, Knight, CJ, Nahir, AM, Martin, G, and Black, CM

Subjects
Systemic scleroderma -- Physiological aspects -- Measurement, Scleroderma (Disease) -- Physiological aspects -- Measurement, Biomechanics -- Measurement -- Physiological aspects, Skin -- Medical examination -- Measurement -- Physiological aspects, Health, Physiological aspects, Medical examination, Measurement
Abstract

Objective: To evaluate biomechanical properties of skin in patients with systemic sclerosis (SSc) using the BTC-2000 suction device. Methods: Twenty five patients with limited cutaneous SSc (lcSSc), 20 patients with [...]

Published
2002

12. Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis

Author

Evans, IC, Barnes, JL, Garner, IM, Pearce, DR, Maher, TM, Shiwen, X, Renzoni, EA, Wells, AU, Denton, CP, Laurent, GJ, Abraham, DJ, and McAnulty, RJ

Subjects
Male, Genotype, Transcription, Genetic, systemic sclerosis, Pulmonary Fibrosis, Down-Regulation, S8, Transfection, fibroblast, Dinoprostone, Epigenesis, Genetic, Humans, RNA, Messenger, Enzyme Inhibitors, Promoter Regions, Genetic, DNA Modification Methylases, Lung, Cells, Cultured, Aged, Cell Proliferation, Original Paper, prostaglandin E2, DNA methylation, Binding Sites, Scleroderma, Systemic, Dose-Response Relationship, Drug, 11 Medical And Health Sciences, Fibroblasts, Middle Aged, idiopathic pulmonary fibrosis, Original Papers, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Phenotype, Cardiovascular System & Hematology, cyclooxygenase-2, Cyclooxygenase 2, Case-Control Studies, Female, RNA Interference
Abstract

The present study demonstrates that hypermethylation and silencing of chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), a transcriptional regulator of cyclooxygenase-2 (COX-2), is a major contributor to failure of fibroblasts to up-regulate COX-2 in pulmonary fibrosis. DNA methyltransferase (DNMT) inhibition reduces c8orf4 methylation, restores COX-2 expression and normalizes fibroblast function., Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E2, due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2′-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE2 production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE2 production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE2 synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4.

Published
2016

13. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Author

Bageghni, SA, Hemmings, KE, Zava, N, Denton, CP, Porter, KE, Ainscough, JFX, Drinkhill, MJ, and Turner, NA

Subjects
cardiovascular system
Abstract

Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol. Cardiac function was assessed by pressure–volume conductance catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular, and molecular levels. Isoproterenol infusion in control mice promoted overt cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end systolic volume, increased cardiac weight index, increased cardiomyocyte area, increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy-associated microRNAs). Fibroblast-specific p38α KO mice exhibited marked protection against myocardial injury, with isoproterenol-induced alterations in cardiac function, histology, and molecular markers all being attenuated. In vitro mechanistic studies determined that cardiac fibroblasts responded to damaged myocardium by secreting several paracrine factors known to induce cardiomyocyte hypertrophy, including IL-6, whose secretion was dependent upon p38α activity. In conclusion, cardiac fibroblast p38α contributes to cardiomyocyte hypertrophy and cardiac dysfunction, potentially via a mechanism involving paracrine fibroblast-to-myocyte IL-6 signaling.—Bageghni, S. A., Hemmings, K. E., Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J., Turner, N. A. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism.

Published
2018

14. A Multicenter Study of the Validity and Reliability of Responses to Hand Cold Challenge as Measured by Laser Speckle Contrast Imaging and Thermography:outcome measures for systemic sclerosis-related Raynaud's phenomenon

Author

Wilkinson, JD, Leggett, SA, Marjanovic, EJ, Moore, TL, Allen, J, Anderson, ME, Britton, J, Buch, MH, Del Galdo, F, Denton, CP, Dinsdale, G, Griffiths, B, Hall, F, Howell, K, MacDonald, A, McHugh, NJ, Manning, JB, Pauling, JD, Roberts, C, Shipley, JA, Herrick, AL, and Murray, AK

Subjects
Male, Immunology, Diagnostic Techniques, Cardiovascular, Contrast Media, Statistics, Nonparametric, Fingers, Rheumatology, Outcome Assessment, Health Care, Humans, Immunology and Allergy, Aged, Observer Variation, Scleroderma, Systemic, Lasers, Reproducibility of Results, Raynaud Disease, Middle Aged, Hand, Cold Temperature, Regional Blood Flow, Thermography, Area Under Curve, Feasibility Studies, Female, Skin Temperature
Abstract

Objective: Reliable and objective outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)–related Raynaud's phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are noninvasive measures of perfusion that have shown excellent potential. This multicenter study was undertaken to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography, and low-cost cell phone/mobile phone thermography (henceforth referred to as mobile thermography) in patients with SSc-related RP. Methods: Patients with RP secondary to SSc were recruited from 6 UK tertiary care centers. The patients underwent cold challenge on 2 consecutive days. Changes in cutaneous blood flow/skin temperature at each visit were imaged simultaneously using LSCI, standard thermography, and mobile thermography. Measurements included area under the curve (AUC) for reperfusion/rewarming and maximum blood flow rate/skin temperature after rewarming (MAX). Test–retest reliability was assessed using intraclass correlation coefficients (ICCs). Estimated latent correlations (estimated from multilevel models, taking values between −1 and 1; denoted as rho values) were used to assess the convergent validity of LSCI and thermography. Results: In total, 159 patients (77% with limited cutaneous SSc) were recruited (84% female, median age 63.3 years). LSCI and standard thermography both had substantial reliability, with ICCs for the reperfusion/rewarming AUC of 0.67 (95% confidence interval [95% CI] 0.54, 0.76) and 0.68 (95% CI 0.58, 0.80), respectively, and ICCs for the MAX of 0.64 (95% CI 0.52, 0.75) and 0.72 (95% CI 0.64, 0.81), respectively. Very high latent correlations were present for the AUCs of LSCI and thermography (ρ = 0.94; 95% CI 0.87, 1.00) and for the AUCs of standard and mobile thermography (ρ = 0.98; 95% CI 0.94, 1.00). Conclusion: This is the first multicenter study to examine the reliability and validity of cold challenge using LSCI and thermography in patients with SSc-related RP. LSCI and thermography both demonstrated good potential as outcome measures. LSCI, standard thermography, and mobile thermography had very high convergent validity.

Published
2018

15. Gender differences in early systemic sclerosis patients: a report from the EULAR scleroderma trials and research group (EUSTAR) database

Author

Carreira, PE, Carmona, L, Joven, BE, Loza, E, Andreu, JL, Riemekasten, G, Vettori, S, Balbir-Gurman, A, Airò, P, Walker, UA, Damjanov, N, Matucci-Cerinic, M, Ananieva, LP, Rednic, S, Czirják, L, Distler, O, Farge, D, Hesselstrand, R, Corrado, A, Caramaschi, P, Tikly, M, Allanore, Y, Valentini, G, Hanes, J, Gabrielli, A, Lapadula, G, Heitmann, S, Valesini, G, von Mühlen, CA, Kucharz, EJ, Cozzi, F, Rozman, B, Pellerito, R, Müller-Ladner, U, Montecucco, C, Smith, V, Jimenez, S, Martinovic, D, Novak, S, Burkhardt, H, Mihai, CM, Pozzi, MR, Vacca, A, Radominski, SC, Chizzolini, C, Krasowska, D, Mouthon, L, Westhovens, R, Mallia, C, Wiland, P, Kummel-Lorenz, B, Vlachoyiannopoulos, P, Hachulla, E, Üprus, M, Sulli, A, Stork, J, Denton, CP, Ortiz, V, Stamenkovic, B, de la Puente, C, Meroni, P, Popa, S, Solanki, K, Becvar, R, Seidel, M, Pereira da Silva, JA, Selmi, CF, Nielsen, H, Aringer, M, Anic, B, and Yavuz, S

Subjects
integumentary system, systemic sclerosis, gender, cohort, skin and connective tissue diseases
Abstract

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (

Published
2018

16. A TNFSF13B Functional Variant Is Not Involved in Systemic Sclerosis and Giant Cell Arteritis Susceptibility

Author

Gonzalez-Serna, D, Carmona, EG, Ortego-Centeno, N, Simeon, CP, Solans, R, Hernandez-Rodriguez, J, Tolosa, C, Castaneda, S, Narvaez, J, Martinez-Valle, F, European GCA Consortium, European Scleroderma Group, Witte, T, Neumann, T, Holle, J, Beretta, L, Boiardi, L, Emmi, G, Cimmino, MA, Vaglio, A, Herrick, AL, Denton, CP, Salvarani, C, Cid, MC, Morgan, AW, Fonseca, C, Gonzalez-Gay, MA, Martin, J, Marquez, A, Márquez, Ana [0000-0001-9913-7688], Martín, Javier [0000-0002-2202-0622], Ortego-Centeno, N. [0000-0003-2325-0937], Universidad de Cantabria, Universitat de Barcelona, Márquez, Ana, Martín, Javier, and Ortego-Centeno, N.

Subjects
Male, 0301 basic medicine, Genetics and Molecular Biology (all), B Cells, Genotyping Techniques, Lydia Becker Institute, Physiology, Cooperative research, Biopsy, Autoimmunity, Biochemistry, Temporal Arteritis, Cohort Studies, White Blood Cells, Mathematical and Statistical Techniques, 0302 clinical medicine, INDEL Mutation, immune system diseases, Animal Cells, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Immune Physiology, B-Cell Activating Factor, Medicine and Health Sciences, Gene Regulatory Networks, Molecular genetics, skin and connective tissue diseases, Aged, 80 and over, Innate Immune System, Multidisciplinary, Statistics, Middle Aged, Metaanalysis, TNFSF13B, Systemic Sclerosis, Giant Cell Arteritis, Europe, Thematic network, Physical Sciences, Cytokines, Medicine, Female, Christian ministry, Cellular Types, Research Article, Adult, Immune Cells, Science, Cèl·lules B, Giant Cell Arteritis, Immunology, Library science, Research and Analysis Methods, Genetic Predisposition, Polymorphism, Single Nucleotide, Genètica molecular, Autoimmune Diseases, 03 medical and health sciences, Political science, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Genetics, medicine, Humans, Genetic Predisposition to Disease, Statistical Methods, Antibody-Producing Cells, Aged, 030203 arthritis & rheumatology, B cells, Scleroderma, Systemic, Blood Cells, Biology and Life Sciences, Human Genetics, Cell Biology, Molecular Development, medicine.disease, Giant cell arteritis, 030104 developmental biology, Case-Control Studies, Immune System, Genetics of Disease, Clinical Immunology, Clinical Medicine, Mathematics, Developmental Biology
Abstract

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc., Funding: This work was supported by the following grants: P12-BIO-1395 from Consejería de Innovación, Ciencia y Tecnología, Junta de Andalucía (Spain) (JM), and the Cooperative Research Thematic Network (RETICS) programme (RD16/0012/0013) (RIER) (JM), from Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Economy, Industry and Competitiveness). AM is recipient of a Miguel Servet fellowship (CP17/00008) from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness) (AM).

Published
2018

17. S143 Serum CYFRA 21–1 as a prognostic marker in scleroderma-associated interstitial lung disease

Author

Stock, CJW, primary, Hoyles, R, additional, D’accord, C, additional, Kokosi, M, additional, Alfieri, V, additional, Campochiaro, C, additional, Donovan, J, additional, Mori, L, additional, Maher, TM, additional, Kouranos, V, additional, Margaritopoulos, G, additional, George, PM, additional, Molyneaux, PL, additional, Chua, F, additional, Abraham, DJ, additional, Ong, V, additional, Denton, CP, additional, Wells, AU, additional, and Renzoni, EA, additional

Published
2018
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18. Proposal for a Juvenile Systemic Sclerosis Response Index(JSScRI): Result of the Consensus Meeting in Hamburg. Germany 11th of December 2016

Author

Foeldvari, I, Furst, D, Anton, J, Baildem, E, Blakley, M, Constantin, T, Costa Reis, P, Curran, M, Cutolo, M, Denton, CP, Fligelstone, K, Hinrichs, B, Ingegnoli, F, Kienast, A, Nemcova, D, Pain, C, Pilkington, C, Smith, V, and Khanna, D

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Juvenile Systemic Sclerosis (jSSc) is an orphan disease. There is increaseing interest to test novel therapies in management of fibrotic diseases. Therefore, is very important to develop a Response Index for jSSc (JSScRI) to separate effective therapies from placebo. In 2014 at the First[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Published
2017
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19. Short term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis

Author

Goh, NS, Hoyles, RK, Denton, CP, Hansell, DM, Renzoni, EA, Maher, TM, Nicholson, AG, Wells, AU, National Institute for Health Research, Arthritis Research UK, and Raynaud's and Scleroderma Association

Subjects
PNEUMONIA, Adult, Male, Pulmonary Fibrosis, Vital Capacity, Severity of Illness Index, Rheumatology, SCLERODERMA, END-POINTS, Humans, COMPUTED-TOMOGRAPHY, Lung, CRYPTOGENIC FIBROSING ALVEOLITIS, DECLINE, Science & Technology, Scleroderma, Systemic, respiratory system, Middle Aged, Prognosis, United Kingdom, respiratory tract diseases, Respiratory Function Tests, Multivariate Analysis, SURVIVAL, Disease Progression, ARTERIAL-HYPERTENSION, Pulmonary Diffusing Capacity, Female, Lung Diseases, Interstitial, Life Sciences & Biomedicine, FORCED VITAL CAPACITY, CLINICAL-TRIALS
Abstract

OBJECTIVE: To determine the prognostic value of pulmonary function test (PFT) trends at one and two years in interstitial lung disease associated with systemic sclerosis (SSc-ILD). METHODS: The prognostic significance of PFT trends at one year (n=162), and two years (n=140) was examined against 15 year survival. PFT trends, expressed as continuous and categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-ILD was defined at presentation as limited lung fibrosis or extensive lung fibrosis using the UKRSA staging system. RESULTS: One year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical FVC change, alone or in combination with categorical change in DLco, had greater prognostic significance than continuous FVC change or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite, consisting of either an FVC decline from baseline ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At two years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in limited lung fibrosis. However, in extensive lung fibrosis, the composite end-point defined above was the strongest prognostic determinant. Larger changes were required in the FVC/DLco ratio than in Kco to achieve prognostic significance. CONCLUSION: Our findings provide support for routine spirometric and gas transfer monitoring in SSc-ILD, based on linkages to long-term outcome, with further evaluation of a composite FVC and DLco end-point warranted for trial purposes. This article is protected by copyright. All rights reserved.

Published
2017

21. There is a need for new systemic sclerosis subset criteria. A content analytic approach

Author

Johnson, SR, primary, Soowamber, ML, additional, Fransen, J, additional, Khanna, D, additional, Van Den Hoogen, F, additional, Baron, M, additional, Matucci-Cerinic, M, additional, Denton, CP, additional, Medsger, TA, additional, Carreira, PE, additional, Riemekasten, G, additional, Distler, J, additional, Gabrielli, A, additional, Steen, V, additional, Chung, L, additional, Silver, R, additional, Varga, J, additional, Müller-Ladner, U, additional, Vonk, MC, additional, Walker, UA, additional, Wollheim, FA, additional, Herrick, A, additional, Furst, DE, additional, Czirjak, L, additional, Kowal-Bielecka, O, additional, Del Galdo, F, additional, Cutolo, M, additional, Hunzelmann, N, additional, Murray, CD, additional, Foeldvari, I, additional, Mouthon, L, additional, Damjanov, N, additional, Kahaleh, B, additional, Frech, T, additional, Assassi, S, additional, Saketkoo, LA, additional, and Pope, JE, additional

Published
2017
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22. Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies

Author

López-Isac E, Martín JE, Assassi S, Simeón CP, Carreira P, Ortego-Centeno N, Freire M, Beltrán E, Narváez J, Alegre-Sancho JJ, Spanish Scleroderma Group, Fernández-Gutiérrez B, Balsa A, Ortiz AM, González-Gay MA, Beretta L, Santaniello A, Bellocchi C, Lunardi C, Moroncini G, Gabrielli A, Witte T, Hunzelmann N, Distler JH, Riekemasten G, van der Helm-van Mil AH, de Vries-Bouwstra J, Magro-Checa C, Voskuyl AE, Vonk MC, Molberg Ø, Merriman T, Hesselstrand R, Nordin A, Padyukov L, Herrick A, Eyre S, Koeleman BP, Denton CP, Fonseca C, Radstake TR, Worthington J, Mayes MD, Martín J, University of Queensland [Brisbane], Rheumatology Service, Hospital Clínico San Carlos, University Hospital La Paz, Madrid, Referral Center for Systemic Autoimmune Diseases, University of Milan, Department of Clinical and Experimental Medicine, University of Verona (UNIVR), Department of Dermatology, University of Cologne, Department of Internal Medicine 3, Institute for Clinical Immunology Erlangen-Nuremberg, Karolinska Institutet [Stockholm], University Medical Center [Utrecht], Laboratory of Translational Immunology [Utrecht, the Netherlands], Institute of Parasitology and Biomedicine (IPB - GRANADA), Spanish National Research Council (CSIC), Immunologie et Pathologie (EA 2216), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Brest, and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Scleroderma, Systemic, integumentary system, [SDV]Life Sciences [q-bio], Arthritis, Rheumatoid, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Genetic Loci, Risk Factors, Interferon Regulatory Factors, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract

Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc-RA genetic loci have been identified independently. The aim of the current study was to systematically search for new common SSc-RA loci through an interdisease meta-genome-wide association (meta-GWAS) strategy. The study was designed as a meta-analysis combining GWAS data sets of patients with SSc and patients with RA, using a strategy that allowed identification of loci with both same-direction and opposite-direction allelic effects. The top single-nucleotide polymorphisms were followed up in independent SSc and RA case-control cohorts. This allowed an increase in the sample size to a total of 8,830 patients with SSc, 16,870 patients with RA, and 43,393 healthy controls. This cross-disease meta-analysis of the GWAS data sets identified several loci with nominal association signals (P This study identified a novel shared locus, IRF4, for the risk of SSc and RA, and highlighted the usefulness of a cross-disease GWAS meta-analysis strategy in the identification of common risk loci.

Published
2016

25. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis

Author

Khanna, D, Denton, Cp, Merkel, Pa, Krieg, T, Le Brun FO, Marr, A, Papadakis, K, Pope, J, Matucci Cerinic, M, Furst, De, Zochling, J, Stevens, W, Proudman, S, Feenstra, J, Youssef, P, Soroka, N, Tyabut, T, Mikhailova, Ei, Rashkov, R, Batalov, A, Yablanski, K, Keystone, E, Jones, N, Dunne, J, Masetto, A, Calabresse, Rj, Cabezas, Pc, Silva, Mo, Sariego, Ia, Escalente, Wj, Anić, B, Kaliterna, Dm, Morović Vergles, J, Novak, S, Prus, V, Artuković, M, Soukup, T, Bečvař, R, Fojtík, Z, Mouthon, L, Kollert, F, Krieg, Tm, Riemekasten, G, Lahner, N, Fierlbeck, G, Ahmadi Simab, K, Diehm, C, Szücs, G, Kumánovics, G, Nagy, G, Pal, S, Veeravalli, Sc, Danda, D, Ferri, Clodoveo, Cerinic, Mm, Cozzi, F, Ferraccioli, G, Wiland, P, Rudnicak, L, Zwolak, R, Roszkiewicz, J, Oleynikov, V, Nikulenkova, N, Lesnyak, O, Kaydashev, I, Kurytar, O, Piura, O, Chopyak, V, Chatterjee, S, Hsu, V, Hummers, L, Martin, R, Domsic, R, Schiopu, E, Shanahan, J, Murphy, Ft, Kaine, J, Davis, W, Grau, R, Eimon, A, Catoggio, Lj, Laborde, Ha, Caeiro, F, Savio, Vg, Amitrano, Cb, Vanthuyne, M, Zeng, X, Zhang, X, Zhu, P, Velásquez Franco CJ, Choueka, Ps, Sanchez, Pj, Hermann, W, Sticherling, M, Steinbrink, K, Hein, R, Aschoff, R, Sfikakis, P, Settas, L, Fraser, A, Veale, D, Balbir Gurman, A, Lidar, M, Litinsky, I, Levy, Y, Carrillo Vazquez SM, Rodriguez Reyna, T, Medrano Ramirez, G, Morales Torres, J, Pacheco Tena CF, Sanchez Ortiz, A, Vonk, Mc, Stebbings, S, Solanki, K, Steele, R, Ng, Kp, Zubrzycka Sienkiewicz, A, Brzosko, M, Szepietowski, Jc, Hrycaj, P, da Silva IF, dos Santos Lda, C, Coelho, Pj, Rios, G, Chernykh, T, Grunina, E, Stanislav, M, Ally, M, Kalla, A, Birlik, Am, Kovalenko, V, Petrov, A, Shevchuk, S, Stanislavchuk, M, Anderson, M, Herrick, A, Belch, J, Chung, L, Csuka, Me, Frech, T, Goldberg, A, Kahaleh, B, Mayes, Md, Rothfield, N, Simms, Rw, Spiera, R, Steen, V, Varga, J, Sikes, D, Derk, Ct, Kohen, M. D., and UCL - (SLuc) Service de rhumatologie

Subjects
0301 basic medicine, Male, Settore MED/16 - REUMATOLOGIA, systemic sclerosis, Peripheral edema, Administration, Oral, law.invention, Scleroderma, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Sulfonamides, Endothelin-1, Medicine (all), General Medicine, Middle Aged, Administration, Female, medicine.symptom, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, Oral, medicine.medical_specialty, Double-Blind Method, Fingers, Humans, Outcome Assessment (Health Care), Pyrimidines, Scleroderma, Systemic, Skin Ulcer, Anemia, Macitentan, Digital Ulcers, Systemic Sclerosis, Placebo, 03 medical and health sciences, Internal medicine, medicine, Adverse effect, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, Macitentan, 030203 arthritis & rheumatology, business.industry, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Systemic, Skin ulcer, medicine.disease, Surgery, Clinical trial, 030104 developmental biology, chemistry, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], business
Abstract

Contains fulltext : 172407.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker. OBJECTIVE: To evaluate the efficacy of macitentan in reducing the number of new digital ulcers in patients with systemic sclerosis. DESIGN, SETTING, AND PARTICIPANTS: Two international, randomized, double-blind, placebo-controlled trials (DUAL-1, DUAL-2) were conducted between January 2012 and February 2014. Participants were patients with systemic sclerosis and active digital ulcers at baseline. Target enrollment for each study was 285 patients. INTERVENTIONS: Patients were randomized (1:1:1) to receive oral doses of 3 mg of macitentan, 10 mg of macitentan, or placebo once daily and stratified according to number of digital ulcers at baseline (3). MAIN OUTCOMES AND MEASURES: The primary outcome for each trial was the cumulative number of new digital ulcers from baseline to week 16. Treatment effect was expressed as the ratio between treatment groups. RESULTS: In DUAL-1, among 289 randomized patients (mean age 51.2 years; 85.8% women), 226 completed the study. The adjusted mean number of new digital ulcers per patient over 16 weeks was 0.94 in the 3-mg macitentan group (n = 95) and 1.08 in the 10-mg macitentan group (n = 97) compared with 0.85 in the placebo group (n = 97) (absolute difference, 0.09 [95% CI, -0.37 to 0.54] for 3 mg of macitentan vs placebo and 0.23 [-0.27 to 0.72] for 10 mg of macitentan vs placebo). Among 265 patients randomized in DUAL-2 (mean age 49.6 years; 81.9% women), 216 completed the study. In DUAL-2, the adjusted mean number of new digital ulcers was 1.44 in the 3-mg macitentan group (n = 88) and 1.46 in the 10-mg macitentan group (n = 88) compared with 1.21 in the placebo group (n = 89) (absolute difference, 0.23 [95% CI, -0.35 to 0.82] for 3 mg of macitentan vs placebo and 0.25 [95% CI, -0.34 to 0.84] for 10 mg of macitentan vs placebo). Adverse events more frequently associated with macitentan than with placebo were headache, peripheral edema, skin ulcer, anemia, upper respiratory tract infection, diarrhea, and nasopharyngitis. CONCLUSIONS AND RELEVANCE: Among patients with systemic sclerosis and active ischemic digital ulcers, treatment with macitentan did not reduce new digital ulcers over 16 weeks. These results do not support the use of macitentan for the treatment of digital ulcers in this patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01474109, NCT01474122.

Published
2016

26. Combined Pulmonary Fibrosis and Emphysema in Scleroderma-Related Lung Disease Has a Major Confounding Effect on Lung Physiology and Screening for Pulmonary Hypertension

Author

Antoniou, KM, Margaritopoulos, GA, Goh, NS, Karagiannis, K, Desai, SR, Nicholson, AG, Siafakas, NM, Coghlan, JG, Denton, CP, Hansell, DM, and Wells, AU

Subjects
ALVEOLITIS, EXPRESSION, MANIFESTATIONS, Science & Technology, Rheumatology, SYSTEMIC-SCLEROSIS, RESOLUTION COMPUTED-TOMOGRAPHY, EXTENT, ARTERIAL-HYPERTENSION, COPD, CT FEATURES, Life Sciences & Biomedicine, RHEUMATOID-ARTHRITIS
Published
2015

27. Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: A Delphi consensus study with cluster analysis

Author

Distler, O, Behrens, F, Pittrow, D, Huscher, D, Denton, Cp, Foeldvari, I, Humbert, M, Matucci Cerinic, M, Nash, P, Opitz, Cf, Rubin, Lj, Seibold, Jr, Furst, De, EPOSS Omeract Group including Ahmadi Simab, K, Albera, Carlo, Bolster, Mb, Brühlmann, P, Burger, C, Chan, K, Chatterjee, S, Clements, P, Confalonieri, M, Csuka, Me, Farber, H, Fessler, B, Foley, R, Frantz, R, Gran, Jt, Highland, K, Hoeper, M, Hsu, V, Inanc, M, Jansa, P, Johnson, S, Kahaleh, B, Kawut, Sm, Keogh, A, Khanna, D, Kähler, Cm, Lang, I, Mahmud, Th, Mandel, J, Mathier, M, Mayes, M, Mchugh, N, Mckown, K, Mclaughlin, V, Medsger TA Jr, Mehta, S, Merkel, Pa, Mubarak, K, Nathan, S, Oudiz, R, Palevsky, H, Park, M, Pope, J, Presberg, K, Ralph, D, Rich, S, Rothfield, N, Rubenfire, M, Scorza, R, Senecal, Jl, Shanahan, J, Silver, R, Staehler, G, Steen, V, Strange, C, Sweiss, N, Taichman, D, Talwar, A, Voskuyl, A, Wigley, F, Williamson, T, Wollheim, F., and University of Zurich

Subjects
Cardiac Catheterization, medicine.medical_specialty, Delphi Technique, Visual analogue scale, Hypertension, Pulmonary, 2745 Rheumatology, Immunology, Delphi method, Placebo-controlled study, Blood Pressure, 610 Medicine & health, Severity of Illness Index, law.invention, Rheumatology, Quality of life, Randomized controlled trial, law, Outcome Assessment, Health Care, Severity of illness, Cluster Analysis, Immunology and Allergy, Medicine, Pharmacology (medical), Randomized Controlled Trials as Topic, Scleroderma, Systemic, business.industry, 10051 Rheumatology Clinic and Institute of Physical Medicine, Clinical trial, Blood pressure, Echocardiography, Exercise Test, Quality of Life, Physical therapy, business
Abstract

Objective. Outcome measures for pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) are only partially validated. The aim of the present study was to establish an expert consensus regarding which outcome measures are most appropriate for clinical trials in PAH-SSc. Methods. Sixty-nine PAH-SSc experts (rheumatologists, cardiologists, pulmonologists) rated a list of disease domains and measurement tools in an Internet-based 3-stage Delphi consensus study. In stages 2 and 3, the medians of domains and measurement tools and frequency distributions of ratings, along with requests for re-ratings, were distributed to respondents to provide feedback. A final score of items was identified by means of cluster analysis. Results. The experts judged the following domains and tools as most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure and cardiac function both measured by right heart catheterization and echocardiography, exercise testing measured by 6-minute walking test and oxygen saturation at exercise, severity of dyspnea measured on a visual analog scale, discontinuation of treatment measured by (serious) adverse events, quality of life/activities of daily living measured by the Short Form 36 and Health Assessment Questionnaire disability index, and global state assessed by physician measured by survival. Conclusion. Among experts in PAH-SSc, a core set of outcome measures has been defined for clinical trials by Delphi consensus methods. Although these outcome measures are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present measures, as well as potential research measures, in further studies.

Published
2008

32. OP0034 Factors associated with disease progression in early-diagnosed pulmonary arterial hypertension associated with systemic sclerosis: longitudinal data from the detect cohort

Author

Mihai, C, primary, Antic, M, additional, Dobrota, R, additional, Bondermann, D, additional, Chadha-Boreham, H, additional, Coghlan, G, additional, Denton, CP, additional, Doelberg, M, additional, Grünig, E, additional, Khanna, D, additional, McLaughlin, VV, additional, Müller-Ladner, U, additional, Pope, JE, additional, Rosenberg, DM, additional, Seibold, JR, additional, Vonk, MC, additional, and Distler, O, additional

Published
2017
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37. P1007Aortic root diameters and aortic regurgitation in hypertensive patients and normal subjectsP1008Ultrasonic assessment of backscatter signal intensity of the right ventricle in patients with arterial hypertension as a method of measuring alterations of myocardiumP1009Speckle strain echocardiography for the evaluation of left ventricular dyssynchrony in patients with severe lung diseases and pulmonary hypertensionP1010Impaired left ventricular ejection fraction in a cohort of systemic sclerosis patients: clinical and echocardiographic characteristicsP1011Prognostic role of subclinical left ventricular systolic dysfunction evaluated using strain imaging by speckle-tracking echocardiographyP1012Inferior vena cava diameter is a strong and practical marker of physical activity and fitnessP1013When the heart works for two: morphologic and functional adaptation during pregnancyP1014Extensive use of lung ultrasound in pediatric cardiac surgery: preliminary experienceP1015Asymptomatic delayed right ventricular perforation by cardiac implantable electronic devices lead, echocardiographic featuresP1016Novel echocardiographic prognostic markers for cardiac tamponade in patients with large malignant pericardial effusions. A paradigm shift from flow to tissue imagingP1017Doppler echocardiographic parameters as a marker of cardiac tamponadeP1018Sigmoid septum as a marker of elongation of thoracic aorta caused by progression of atherosclerosisP1019Carotid artery atherosclerosis and stiffness: comparison of different metabolic measuresP1020Feasibility of triple imaging vasodilator stress echo in patients with suspected coronary artery diseaseP1022The use of combined echo and cardio-pulmonary stress for discriminating cardiac problems from de-conditioning in patients with dyspneaP1023Long-term prognosis of a stress echocardiography in patients after successful primary percutaneous intervention and incomplete revascularization of non-culprit lesionsP1024Diastolic exercise stress echo can unmask diastolic dysfunction in type 2 diabetes, a five-year follow-up studyP1025Diabetes mellitus is the major limitation for diagnosis of coronary artery disease assessed by semisupine ergometer stress echocardiographyP1026Longitudinal changes of atherosclerotic features in the aorta on transcatheter aortic valve implantation using transesophageal echocardiographyP1027Severe aortic stenosis: comparison between effective and anatomical aortic?valvular area by two and three dimension transesophageal ecocardiographyP1028Region growing method provides better left ventricular volume and cardaic output measuringP10293 dimensional echocardiographic evaluation of mitral valve geometry in patients with secondary and primary mitral regurgitationP1030The impact of adjustable region of interest on ventricular strain measurements and arrhythmic risk assessment in patients with hypertrophic cardiomyopathyP1031Left ventricular strain at presentation predicts long-term outcome in ALCAPA patientsP1032Global atrial-ventricular strain as a new index of subclinical left heart dysfunction in hypertensive and diabetic patients

Author

Vriz, O., primary, Ivanov, S., primary, Szulik, M., primary, Llerena Butron, S., primary, Cioffi, G., primary, Bruin De- Bon, HACM, primary, Meras Colunga, P., primary, Cantinotti, M., primary, Zaborska, B., primary, Chalikias, G., primary, Son, JW., primary, Wada, Y., primary, Di Nora, C., primary, Ciampi, Q., primary, Topilsky, YT., primary, Petrovic, MT., primary, Bjork Ingul, C., primary, Tsai, HR., primary, Bando, M., primary, Perea, G., primary, Cheng, H-L, primary, Schueler, R., primary, Rosca, M., primary, Di Salvo, G., primary, Cameli, M., primary, Bertn, NB., additional, Brosolo, G., additional, Bossone, E., additional, Matveev, V., additional, Kuznetsova, L., additional, Dmitrieva, I., additional, Nowak, J., additional, Skowron, W., additional, Klys, J., additional, Koziel, M., additional, Streb, W., additional, Rozentryt, P., additional, Zeglen, S., additional, Kalarus, Z., additional, Kukulski, T., additional, Denton, CP., additional, Coghlan, JG., additional, Schreiber, BE., additional, Viapiana, O., additional, Ognibeni, F., additional, Dalbeni, A., additional, Giollo, A., additional, Gatti, D., additional, Idolazzi, L., additional, Cherubini, A., additional, Mazzone, C., additional, Faganello, G., additional, Di Lenarda, A., additional, Rossini, M., additional, Jorstad, HT., additional, Boekholdt, SM., additional, Panhuyzen-Goedkoop, NM., additional, Bouma, BJ., additional, Peters, RJG, additional, Prado Diaz, S., additional, Montoro Lopez, N., additional, Gonzalez Fernandez, O., additional, Rial Baston, V., additional, Valbuena Lopez, SC., additional, Refoyo Salicio, E., additional, Moreno Yanguela, M., additional, De?La?Calle, M., additional, Bartha Rasero, JL., additional, Dalmau Gonzalez-Gallarza, R., additional, Lopez Sendon, JL., additional, Guzman Martinez, G., additional, Ait-Ali, L., additional, Franchi, EF., additional, Scalese, M., additional, Gargani, L., additional, Makowska, E., additional, Pilichowska-Paszkiet, E., additional, Sikora-Frac, M., additional, Czepiel, A., additional, Swiatkowski, M., additional, Kulakowski, P., additional, Samaras, A., additional, Kikas, P., additional, Thomaidis, A., additional, Drosos, I., additional, Tziakas, D., additional, Kim, HJ., additional, Kim, BJ., additional, Choi, KW., additional, Nam, JH., additional, Lee, JH., additional, Lee, CH., additional, Kim, W., additional, Park, JS., additional, Shin, DG., additional, Kim, YJ., additional, Choi, JH., additional, Fujii, A., additional, Ariyoshi, T., additional, Okuda, S., additional, Omuro, A., additional, Hisaoka, M., additional, Nao, T., additional, Yamasaki, T., additional, Tanaka, N., additional, Yano, M., additional, Poli, S., additional, Vriz, O., additional, Sparacino, L., additional, Zito, C., additional, Carerj, S., additional, Pavan, D., additional, Antonini-Canterin, F., additional, Paterni, M., additional, Villari, B., additional, Picano, E., additional, Rozenbaum, ZR., additional, Khoury, KS., additional, Keren, GK., additional, Giga, V., additional, Stepanovic, J., additional, Boskovic, N., additional, Trifunovic, D., additional, Aleksandric, S., additional, Nedeljkovic, I., additional, Tesic, M., additional, Dobric, M., additional, Rakocevic, I., additional, Beleslin, B., additional, Djordjevic-Dikic, A., additional, Timilsina, AS., additional, Hollekim-Strand, SM., additional, Liu, YW., additional, Tsai, WC., additional, Nishigami, K., additional, Horibata, Y., additional, Nakao, K., additional, Sakamoto, T., additional, Lombardero, M., additional, Henquin, R., additional, Corneli, MC., additional, Oeztuerk, C., additional, Weber, M., additional, Welz, A., additional, Werner, N., additional, Nickenig, G., additional, Hammerstingl, C., additional, Mandes, L., additional, Calin, A., additional, Beladan, CC., additional, Enache, R., additional, Mateescu, A., additional, Calin, C., additional, Jurcut, R., additional, Ginghina, C., additional, Popescu, BA., additional, Muhanna, N., additional, Siblini, G., additional, Bulbul, Z., additional, Issa, Z., additional, Abu Hazeem, A., additional, Fadel, B., additional, Pergola, V., additional, Halees, Z., additional, Fayyadh, M., additional, Mandoli, GE., additional, Righini, FM., additional, Albizzi, C., additional, Capitani, E., additional, Pastore, C., additional, D'ascenzi, F., additional, Focardi, M., additional, and Mondillo, S., additional

Published
2016
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40. Expert agreement on EULAR/EUSTAR recommendations for the management of systemic sclerosis

Author

Walker, Kyle M., Pope, Janet, Alkassab, F, Molitor, Ja, Shapiro, Ls, Fessler, Bj, Gran, Jt, Goldberg, A, Medsger, TA Jr, VALENTINI, Gabriele, Csuka, Me, Griffing, L, Herrick, A, Connolly, M, Vacca, A, Riemekasten, G, Wigley, Fm, Farge, D, Johnson, Sr, Matucci Cerinic, M, Czirjak, L, Toloza, Sm, Mahmud, Th, Frech, Tm, Voskuyl, Ae, Merkel, Pa, Domsic, R, Emery, P, Steen, V, Rudnicka, L, Denton, Cp, Clements, Pj, Chatterjee, S, Kahaleh, B, Hayat, S, Mouthon, L, Lafyatis, R, Lally, Ev, Krieg, T, Chung, L, Catoggio, Lj, Mayes, Md, Anderson, Me, Silver, R, Proudman, S, Seibold, Jr, Senécal, Jl, Stevens, W, Hachulla, E, Inanc, M, Wollheim, F, Distler, O, Katsumoto, Tr, Hsu, V, Collier, Dh, Furst, D, Mckown, K, Khanna, D, Volkov, S, Mathieu, A, Baron, M, Kaminska, Ea, Khalidi, Na, Hudson, M, Markland, J, Masetto, A, Docherty, P., Walker, Kyle M., Pope, Janet, Alkassab, F, Molitor, Ja, Shapiro, L, Fessler, Bj, Gran, Jt, Goldberg, A, Medsger, TA Jr, Valentini, Gabriele, Csuka, Me, Griffing, L, Herrick, A, Connolly, M, Vacca, A, Riemekasten, G, Wigley, Fm, Farge, D, Johnson, Sr, Matucci Cerinic, M, Czirjak, L, Toloza, Sm, Mahmud, Th, Frech, Tm, Voskuyl, Ae, Merkel, Pa, Domsic, R, Emery, P, Steen, V, Rudnicka, L, Denton, Cp, Clements, Pj, Chatterjee, S, Kahaleh, B, Hayat, S, Mouthon, L, Lafyatis, R, Lally, Ev, Krieg, T, Chung, L, Catoggio, Lj, Mayes, Md, Anderson, Me, Silver, R, Proudman, S, Seibold, Jr, Senécal, Jl, Stevens, W, Hachulla, E, Inanc, M, Wollheim, F, Distler, O, Katsumoto, Tr, Hsu, V, Collier, Dh, Furst, D, Mckown, K, Khanna, D, Volkov, S, Mathieu, A, Baron, M, Kaminska, Ea, Khalidi, Na, Hudson, M, Markland, J, Masetto, A, and Docherty, P.

Subjects
Canada, Scleroderma, Systemic, Hypertension, Pulmonary, Skin Disease, Immunology, Health Survey, Sulfonamide, Epoprostenol, Scleroderma, Europe, Systemic sclerosi, Methotrexate, Treatment Outcome, Rheumatology, North America, Vascular Disease, Practice Guidelines as Topic, Immunology and Allergy, Iloprost, Survey, Societies, Medical, Treatment guideline, Human
Abstract

Objective. The European League Against Rheumatism/EULAR Scleroderma Trials and Research group (EULAR/EUSTAR) has published recommendations for the management of systemic sclerosis (SSc). Members of the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research Group were surveyed regarding their level of agreement with the recommendations. Methods. A survey containing the 14 EULAR/EUSTAR recommendations asked participants to indicate their level of agreement with each on a 10-point scale, from 0 (not at all) to 9 (completely agree). The survey was sent to 117 people, and 66 replies were received (56% response rate). Results. Exceptions to generally high agreement included the use of iloprost and bosentan for digital vasculopathy, methotrexate for skin involvement, and bosentan and epoprostenol for pulmonary arterial hypertension (PAH; all < 69% agreement, defined as ≥ 7 rating). Vasculopathy and PAH treatment had differences in agreement between North America and Europe (p < 0.006). Respondents who were EULAR/EUSTAR recommendation authors shared a similar level of agreement compared to those who were not, except for the use of proton pump inhibitors for the prevention of SSc-related gastroesophageal reflux disease, esophageal ulcers, and strictures. Conclusion. EULAR/EUSTAR recommendations were relatively well accepted among SSc experts. Overall reduced agreement may be due to the modest efficacy of some agents (such as methotrexate for the skin). Some regional disagreement is likely because of access differences. The Journal of Rheumatology Copyright © 2011. All rights reserved.

Published
2011

41. Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease Related Interstitial Lung Diseases

Author

Saketkoo, La, Mittoo, S, Frankel, S, Lesage, D, Sarver, C, Phillips, K, Strand, V, Matteson, El, OMERACT Baughman RP, Brown, Kk, Christmann, Rb, Dellaripa, P, Denton, Cp, Distler, O, Fischer, A, Flaherty, K, Huscher, D, Khanna, D, Kowal Bielecka, O, Merkel, Pa, Oddis, Cv, Pittrow, D, Sandorfi, N, Seibold, Jr, Swigris, J, Wells, A, Antoniou, K, Castelino, Fv, Christopher Stine, L, Collard, Hr, Cottin, V, Danoff, S, Hedlund, R, Highland, Kb, Hummers, L, Lynch, Da, Kim, Ds, Ryu, Jh, Miller, Fw, Nichols, K, Proudman, Sm, Richeldi, L, Shah, Aa, van den Assum, P, Aggarwal, R, Ainslie, G, Alkassab, F, Allanore, Y, Anderson, Me, Andonopoulos, Ap, Antin Ozerkis, D, Arrobas, A, Ascherman, Dp, Assassi, S, Baron, M, Bathon, Jm, Baughman, Rp, Behr, J, Beretta, L, Bingham, Co, Binnie, M, Birring, Ss, Boin, F, Bongartz, T, Bourdin, A, Bouros, D, Brasington, R, Bresser, P, Buch, Mh, Burge, Ps, Carmona, L, Carreira, Pe, Carvalho, Cr, Catoggio, Lj, Chan, Km, Chapman, J, Chatterjee, S, Chua, F, Chung, L, Conron, M, Corte, T, Cosgrove, G, Costabel, U, Cox, G, Crestani, B, Crofford, Lj, Csuka, Me, Curbelo, P, Czirják, L, Daniil, Z, D'Arsigny, Cl, Davis, Gs, de Andrade JA, Dellaripa, Pf, De Vuyst, P, Dempsey, Oj, Derk, Ct, Distler, J, Dixon, Wg, Downey, G, Doyle, Mk, Drent, M, Durairaj, L, Emery, P, Espinoza, Lr, Farge, D, Fathi, M, Fell, Cd, Fessler, Bj, Fitzgerald, Je, Flaherty, Kr, Foeldvari, I, Fox, Ga, Frech, Tm, Freitas, S, Furst, De, Gabrielli, A, García Vicuña, R, Georgiev, Ob, Gerbino, A, Gillisen, A, Gladman, Dd, Glassberg, M, Gochuico, Br, Gogali, A, Goh, Ns, Goldberg, A, Goldberg, Hj, Gourley, Mf, Griffing, L, Grutters, Jc, Gunnarsson, R, Hachulla, E, Hall, Fc, Harari, S, Herrick, Al, Herzog, El, Hesselstrand, R, Highland, K, Hirani, N, Hodgson, U, Hollingsworth, Hm, Homer, Rj, Hoyles, Rk, Hsu, Vm, Hubbard, Rb, Hunzelmann, N, Isasi, Me, Isasi, Es, Jacobsen, S, Jimenez, Sa, Johnson, Sr, Jones, Ch, Kahaleh, B, Kairalla, Ra, Kalluri, M, Kalra, S, Kaner, Rj, Kinder, Bw, Kiter, G, Klingsberg, Rc, Kokosi, M, Kolb, Mr, Kowal Bielecka OM, Kur Zalewska, J, Kuwana, M, Lake, Fr, Lally, Ev, Lasky, Ja, Laurindo, Im, Able, L, Lee, P, Leonard, Ct, Lien, Dc, Limper, Ah, Liossis, Sn, Lohr, Km, Loyd, Je, Lundberg, Ie, Mageto, Yn, Maher, Tm, Mahmud, Th, Manganas, H, Marie, I, Marras, Tk, Martinez, Ja, Martinez, Fj, Mathieu, A, Matucci Cerinic, M, Mayes, Md, Mckown, Km, Medsger, Ta, Meehan, Rt, Mendes, Ac, Meyer, Kc, Millar, Ab, Moğulkoc, N, Molitor, Ja, Morais, A, Mouthon, L, Müller, V, Müller Quernheim, J, Nadashkevich, O, Nador, R, Nash, P, Nathan, Sd, Navarro, C, Neves, S, Noth, I, Nunes, H, Olson, Al, Opitz, Cf, Padilla, M, Pappas, D, Parfrey, H, Pego Reigosa JM, Pereira, Ca, Perez, R, Pope, Je, Porter, Jc, Renzoni, Ea, Riemekasten, G, Riley, Dj, Rischmueller, M, Rodriguez Reyna TS, Rojas Serrano, J, Roman, J, Rosen, Gd, Rossman, M, Rothfield, N, Sahn, Sa, Sanduzzi, A, Scholand, Mb, Selman, M, Senécal, Jl, Seo, P, Shah, A, Silver, Rm, Solomon, Jj, Steen, V, Stevens, W, Strange, C, Sussman, R, Sutton, Ed, Sweiss, Nj, Tornling, G, Tzelepis, Ge, Undurraga, A, Vacca, A, Vancheri, Carlo, Varga, J, Veale, Dj, Volkov, S, Walker, Ua, Wells, Au, Wencel, M, Wesselius, Lj, Wickremasinghe, M, Wilcox, P, Wilsher, Ml, Wollheim, Fa, Wuyts, Wa, Yung, G, Zanon, P, Zappala, Cj, Groshong, Sd, Leslie, Ko, Myers, Jl, Padera, Rf, Desai, Sr, Goldin, J, Kazerooni, Ea, Klein, Js, and Keen, Kj

Subjects
Male, medicine.medical_specialty, Delphi Technique, Consensus Development Conferences as Topic, Health Personnel, Immunology, Context (language use), Disease, Severity of Illness Index, Article, Idiopathic pulmonary fibrosis, Rheumatology, medicine, Immunology and Allergy, Humans, Disease management (health), Intensive care medicine, Connective Tissue Diseases, Randomized Controlled Trials as Topic, business.industry, Interstitial lung disease, Disease Management, respiratory system, Focus Groups, medicine.disease, Comorbidity, Connective tissue disease, respiratory tract diseases, Clinical trial, Treatment Outcome, Patient Satisfaction, Physical therapy, Quality of Life, ÍNDICE DE GRAVIDADE DA DOENÇA, Interdisciplinary Communication, business, Lung Diseases, Interstitial
Abstract

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Published
2014

44. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: Provisional core sets of domains and instruments for use in clinical trials

Author

Saketkoo, La, Mittoo, S, Huscher, D, Khanna, D, Dellaripa, Pf, Distler, O, Flaherty, Kr, Frankel, S, Oddis, Cv, Denton, Cp, Fischer, A, Kowal Bielecka OM, Lesage, D, Merkel, Pa, Phillips, K, Pittrow, D, Swigris, J, Antoniou, K, Baughman, Rp, Castelino, Fv, Christmann, Rb, Christopher Stine, L, Collard, Hr, Cottin, V, Danoff, S, Highland, Kb, Hummers, L, Shah, Aa, Kim, Ds, Lynch, Da, Miller, Fw, Proudman, Sm, Richeldi, L, Ryu, Jh, Sandorfi, N, Sarver, C, Wells, Au, Strand, V, Matteson, El, Brown, Kk, Seibold, Jr, Aggarwal, R, Ainslie, G, Alkassab, F, Allanore, Y, Descartes, P, Anderson, Me, Andonopoulos, Ap, Antin Ozerkis, D, Arrobas, A, Ascherman, Dp, Assassi, S, Baron, M, Bathon, Jm, Behr, J, Beretta, L, Bingham, Co, Binnie, M, Birring, Ss, Boin, F, Bongartz, T, Bourdin, A, Bouros, D, Brasington, R, Bresser, P, Buch, Mh, Burge, Ps, Carmona, L, Carreira, Pe, Carvalho, Cr, Catoggio, Lj, Chan, Km, Chapman, J, Chatterjee, S, Chua, F, Chung, L, Conron, M, Corte, T, Cosgrove, G, Costabel, U, Cox, G, Crestani, B, Crofford, Lj, Csuka, Me, Curbelo, P, László, C, Daniil, Z, D'Arsigny, Cl, Davis, Gs, de Andrade JA, De Vuyst, P, Dempsey, Oj, Derk, Ct, Distler, J, Dixon, Wg, Downey, G, Doyle, Mk, Drent, M, Durairaj, L, Emery, P, Espinoza, Lr, Farge, D, Fathi, M, Fell, Cd, Fessler, Bj, Fitzgerald, Je, Fox, Ga, Foeldvari, I, Frech, Tm, Freitas, S, Furst, De, Gabrielli, A, García Vicuña, R, Georgiev, Ob, Gerbino, A, Gillisen, A, Gladman, Dd, Glassberg, M, Gochuico, Br, Gogali, A, Goh, Ns, Goldberg, A, Goldberg, Hj, Gourley, Mf, Griffing, L, Grutters, Jc, Gunnarsson, R, Hachulla, E, Hall, Fc, Harari, S, Herrick, Al, Herzog, El, Hesselstrand, R, Hirani, N, Hodgson, U, Hollingsworth, Hm, Homer, Rj, Hoyles, Rk, Hsu, Vm, Hubbard, Rb, Hunzelmann, N, Isasi, Me, Isasi, Es, Jacobsen, S, Jimenez, Sa, Johnson, Sr, Jones, Ch, Kahaleh, B, Kairalla, Ra, Kalluri, M, Kalra, S, Kaner, Rj, Kinder, Bw, Klingsberg, Rc, Kokosi, M, Kolb, Mr, Kur Zalewska, J, Kuwana, M, Lake, Fr, Lally, Ev, Lasky, Ja, Laurindo, Im, Able, L, Lee, P, Leonard, Ct, Lien, Dc, Limper, Ah, Liossis, Sn, Lohr, Km, Loyd, Je, Lundberg, Ie, Mageto, Yn, Maher, Tm, Mahmud, Th, Manganas, H, Marie, I, Marras, Tk, Antônio Baddini Martinez, J, Martinez, Fj, Mathieu, A, Matucci Cerinic, M, Mayes, Md, Mckown, Km, Medsger, Ta, Meehan, Rt, Cristina, Ma, Meyer, Kc, Millar, Ab, Moğulkoc, N, Molitor, Ja, Morais, A, Luc Mouthon, P, Müller, V, Müller Quernheim, J, Nadashkevich, O, Nador, R, Nash, P, Nathan, Sd, Navarro, C, Neves, S, Noth, I, Nunes, H, Olson, Al, Opitz, Cf, Padilla, M, Pappas, D, Parfrey, H, Pego Reigosa JM, Pereira, Ca, Perez, R, Pope, Je, Porter, Jc, Renzoni, Ea, Riemekasten, G, Riley, Dj, Rischmueller, M, Rodriguez Reyna TS, Rojas, Serrano, Roman, J, Rosen, Gd, Rossman, M, Rothfield, N, Sahn, Sa, Sanduzzi, A, Scholand, Mb, Selman, M, Senécal, Jl, Seo, P, Silver, Rm, Solomon, Jj, Steen, V, Stevens, W, Strange, C, Sussman, R, Sutton, Ed, Sweiss, Nj, Tornling, G, Tzelepis, Ge, Undurraga, A, Vacca, A, Vancheri, Carlo, Varga, J, Veale, Dj, Volkov, S, Walker, Ua, Wencel, M, Wesselius, Lj, Wickremasinghe, M, Wilcox, P, Wilsher, Ml, Wollheim, Fa, Wuyts, Wa, Yung, G, Zanon, P, Zappala, Cj, Groshong, Sd, Leslie, Ko, Myers, Jl, Padera, Rf, Desai, Sr, Goldin, J, Kazerooni, Ea, Klein, Js, Cenac, Sl, Grewal, Hk, Christensen, Am, Ferguson, S, Tran, M, Keen, K. J., Costabel, Ulrich (Beitragende*r), Raynauds & Scleroderma Association, Arthritis Research UK, The Scleroderma Society, and British Lung Foundation

Subjects
Lung Diseases, Connective tissue disease associated lung disease, CTD-ILD Special Interest Group, International Cooperation, Respiratory System, Medizin, Rheumatoid lung disease, Idiopathic pulmonary fibrosis, Quality of life, QUALITY-OF-LIFE, CYCLOPHOSPHAMIDE, SCLERODERMA LUNG, Registries, Connective Tissue Diseases, Societies, Medical, Randomized Controlled Trials as Topic, Interstitial lung disease, respiratory system, Connective tissue disease, Interstitial Fibrosis, medicine.anatomical_structure, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Consensus, Clinical Sciences, END-POINT, Interstitial Lung Disease, Systemic disease and lungs, Medical, medicine, Humans, ENSAIO CLÍNICO CONTROLADO RANDOMIZADO, VALIDITY, Intensive care medicine, Lung, Science & Technology, COUGH, business.industry, Clinical study design, MORTALITY, SYSTEMIC-SCLEROSIS, 1103 Clinical Sciences, Congresses as Topic, medicine.disease, GEORGES RESPIRATORY QUESTIONNAIRE, respiratory tract diseases, Clinical trial, IPF, Physical therapy, Interstitial, Societies, business, Lung Diseases, Interstitial
Abstract

Rationale: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods: The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results: A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion: Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Published
2014

45. Development of a provisional core set of response measures for clinical trials of systemic sclerosis

Author

Khanna D, Lovell DJ, Giannini E, Clements PJ, Merkel PA, Seibold JR, Matucci Cerinic M, Denton CP, Mayes MD, Steen VD, Varga J, Furst DE, Baron M, Csuka ME, Berezne A, Briet SN, Brühlmann P, Buch MH, Catoggio L, Collier D, Crofford L, Czirják L, Derk CT, Distler O, Doyle MK, Farge Bancel D, Fessler B, Foeldvari I, Goldberg A, Gran JT, Grau R, Griffing WL, Hayat S, Herrick AL, Hsu V, Hummers LK, Inanç M, Johnson S, Kahaleh MB, Lafyatis RA, Lee P, Mahmud TH, Malcarne V, McHugh NJ, Martin RW, McKown K, Medsger TA Jr, Moreland L, Pope JE, Rich E, Rothfield NF, Schiopu E, Scorza R, Senécal JL, Shanahan J, Simms RW, Strand V, Silver RM, Sweiss N, van den Hoogen FH, Veale D, Voskuyl AE, Wigley F, Wollheim FA, VALENTINI, Gabriele, Khanna, D, Lovell, Dj, Giannini, E, Clements, Pj, Merkel, Pa, Seibold, Jr, Matucci Cerinic, M, Denton, Cp, Mayes, Md, Steen, Vd, Varga, J, Furst, De, Baron, M, Csuka, Me, Berezne, A, Briet, Sn, Brühlmann, P, Buch, Mh, Catoggio, L, Collier, D, Crofford, L, Czirják, L, Derk, Ct, Distler, O, Doyle, Mk, Farge Bancel, D, Fessler, B, Foeldvari, I, Goldberg, A, Gran, Jt, Grau, R, Griffing, Wl, Hayat, S, Herrick, Al, Hsu, V, Hummers, Lk, Inanç, M, Johnson, S, Kahaleh, Mb, Lafyatis, Ra, Lee, P, Mahmud, Th, Malcarne, V, Mchugh, Nj, Martin, Rw, Mckown, K, Medsger TA, Jr, Moreland, L, Pope, Je, Rich, E, Rothfield, Nf, Schiopu, E, Scorza, R, Senécal, Jl, Shanahan, J, Simms, Rw, Strand, V, Silver, Rm, Sweiss, N, Valentini, Gabriele, van den Hoogen, Fh, Veale, D, Voskuyl, Ae, Wigley, F, and Wollheim, Fa

Subjects
medicine.medical_specialty, Consensus, Delphi Technique, Visual analogue scale, Endpoint Determination, Immunology, Alternative medicine, Delphi method, General Biochemistry, Genetics and Molecular Biology, Article, Rheumatology, Epidemiology, Immunology and Allergy, Medicine, Humans, Multicenter Studies as Topic, computer.programming_language, Core set, Clinical Trials as Topic, Scleroderma, Systemic, business.industry, Outcome measures, Clinical trial, Treatment Outcome, Physical therapy, business, computer, Delphi
Abstract

Objective: To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc). Methods: The Scleroderma Clinical Trials Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains (skin, musculoskeletal, cardiac, pulmonary, cardio-pulmonary, gastrointestinal, renal, Raynaud phenomenon and digital ulcers, health-related quality of life and function, global health, and biomarkers) for SSc clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting, during which the Steering Committee discussed the feasibility, reliability, redundancy and validity of the items. Round 3 sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility but lacked data on reliability and validity, but may still be useful research outcome measures for future trials. Results: A total of 50 SCTC investigators participated in round 1, providing 212 unique items for the 11 domains. In all, 46 (92%) participants responded in round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged to be appropriate for inclusion in a 1-year multi-centre clinical trial. In total, 40 SCTC investigators completed round 3 and ranked 30 of 31 items as acceptable for inclusion in the core set. The Steering Committee also proposed 14 items for a research agenda. Conclusion: Using a Delphi exercise, we have developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc.

Published
2008

46. DUO Registry Group. Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

Author

Guillevin, L, Hunsche, E, Denton, Cp, Krieg, T, Schwierin, B, Rosenberg, D, Matucci Cerinic, M, DUO Registry Group Collaborators Raffier, B, Hirschi, M, Trautinger, F, Schmidt, P, Stetter, M, Hundstorfer, M, Reinhart, V, Monshi, B, Pirkhammer, D, Richter, L, Hamberger, N, Metz, S, Feldmann, R, Semmelweis, K, Lackner, K, Tomi, N, Kolle, H, Hafner, F, Brodmann, M, Kuen Spiegel, M, Minmair, G, Heil, Pm, Broil, H, Holzer, G, Illmer, X, Rintelen, B, Sautner, J, Takacs, M, Thun, M, Zemanova, I, Soukup, T, Smrzova, A, Bohmova, J, Prochazkova, L, Nemec, P, Fojtik, Z, Suchy, D, Becvar, R, Olsen, Ab, Sondergaard, Kh, Luosu jarvi, R, Vidqvist, Kl, Madaule, S, Beneton, N, Maillard, H, Charlanne, H, Granelbrocard, F, Hachulla, E, Hatron, Py, Jourdain, N, Lambert, M, Launay, D, Morell, S, Woijtasik, G, Skowron, F, Zenone, T, Dadban, A, Lok, C, Ferrandiz, D, Magybertrand, N, Moiton, Mp, Taieb, A, Balquiere, S, Belin, E, Droitcourt, C, Julien, S, Prey, S, Boulon, C, Constans, J, Doutre, Ms, Kostrzwewa, E, Richez, C, Greco, M, Misery, L, Sassolas, B, Collet, E, Berthier, S, Leguy Seguin, V, Imbert, B, Carpentier, P, Blaise, S, Couraud, A, Doeffel Hantz, V, Spars, A, Bezanahary, H, Boussely, N, Dumonteil, S, Fauchais, Al, Goudran, G, Loustaud Ratti, V, Manea, P, Vidal, E, Coppere, B, Desmursclavel, H, Girard Madoux MH, Hot, A, Ninet, J, Granel, B, Cohen, Jd, Keynote, A, Khau van Kien, A, Le Quellec, A, Riviere, S, Rullier, P, Bessis, D, Farcas, C, Bravetti, V, Moline, T, Wahl, D, Zuily, S, Granel Brocard, F, Agard, C, Durant, C, Fuzibet, Jg, Queyrel, V, Berezne, A, Mouthon, L, Cabane, J, Tiev, K, Toledano, C, Lazareth, I, Michon Pasturel, U, Priollet, P, Reguiai, Z, Cazaletslacoste, C, Jego, P, Letremy, A, Perlat, A, Duval Modeste AB, Chatelus, E, Chiffot, H, Sibillia, J, Sordet, C, Adoue, D, Couret, B, Moulis, G, Pugnet, G, Sailler, L, Diot, E, Gaches, F, Farge, D, Keshtmand, H, Frances, C, von Elling, A, Bora, D, Ebel, J, Ahmadi Simab, K, Klein, E, Hahn, K, Schulze, K, Rasche, C, Riemekasten, G, Lee, Hh, Deuschle, K, Mattat, K, Becker, M, Worm, M, Mensing, C, Klings, D, Mensing, H, Messall, J, Zuper, R, Eilbacher, P, Saar, P, Kaufmann, P, Hallermann, C, Schmidt, K, Wahn, H, Schildt, K, Schuart, T, Kaczmarczyk, A, Kellner, C, von Oelhafen, J, Baron von Bildering, P, Kunze, S, Kleiner, Hj, Alsheimer, B, Schuetz, N, Miirker Hermann, E, Gottl, Kh, Weiss, E, Reischel, N, Kern, S, Goettl, Kh, Goetheuniversitiitsklinikum, Jw, Himsel, A, Henkemeier, U, Schwarting, A, Hazenbiller, A, Nichelmann, V, Rumbaur, C, Boesenberg, I, Schmeiser, T, Mueller Ladner, U, Unholzer, A, Starz, H, Welzel, J, Plaumann, K, Stoeckl, F, Sperling, S, Podda, M, Wagner, N, Rapprich, H, Niedermeier, A, Messer, G, Sardy, M, Bekou, V, Dill MUller, D, Wlodarz, M, Belloni, B, Huettig, B, Ziai, M, Hein, R, Kneitz, C, Federow, I, Schneider, K, Semmler, M, Hapke, S, Metzler, C, Stein, T, Enderlein, M, Kayser, M, Werthmann, M, Guenther, Cu, Neul, S, Hellmich, B, Loeffler, C, Pflugfelder, J, Karaenke, P, Mueglich, C, Tony, Hp, Marina, P, Popp, M, Mittag, M, Baumann, C, Scheib, Eg, Brand, H, Wilhelm, Hu, Bohm, J, Dyballa, J, Boehm, J, Taggeselle, J, Luthke, K, Wuerzburg, I, Niefanger, K, Mayer, L, Drabek, J, Harmuth, W, Dietl, S, Moritz, D, Gause, A, Gaubitz, M, Hallecker, A, Krupp, E, Rumpel, H, Moosig, F, Frey, P, Kahl, S, Linke, M, Merk, B, Bloching, Hh, Ochs, W, Kurthen, R, Eiden, E, Guertler, I, Aries, Pm, Kirchberg, S, Jahnke, K, Mettler, S, Toeller, S, Zwenger, S, Langer, He, Deininger, F, Hartmann, F, Neeck, G, Neek, G, Wernitzsch, H, Meier, L, Herr, U, Meier, U, Aaig, W, Bruckner, L, Sheikh, N, Wollenhaupt, J, Krog, B, Wollersdorfer, E, Hall, R, Diehm, C, Tiggers, C, Peters, J, Kirschke, J, Schroeder, Jo, Zeuner, R, Uhlig, S, Barth, S, Huegel, R, Glaeser, R, Schaefer, C, Monshausen, M, Mengden, T, Funkert, A, Blank, N, Lupaschko, S, Voss, B, Megahed, M, Sadeghlar, F, Seidel, M, Wasmuth, Jc, Kreuter, A, Vosswinkel, J, Pfoehler, C, Gerber, A, Haust, M, Hoff, Np, Mota, R, Akanay Diesel, S, Homey, B, Katzemich, A, Erfurt Berge, C, Sticherling, M, Beyer, C, Distler, J, Mitchell, A, Freundlieb, C, Rushentsova, U, Hermanns, G, Blaschke, S, Fiene, M, Wessel, C, Norgauer, J, Rabe, B, Schuster, J, Scholz, J, Kremer, K, Robakidze Torbahn, M, Moinzadeh, P, Dohse, A, Muhlack, A, Schultz, L, Schult, S, Frambach, Y, Kruse, S, Kettenbach, A, Fell, I, Schweda, K, Steinbrink, K, Podobinska, M, Fieri beck, G, Schanz, S, Pfeiffer, C, Hassel, R, Herrgott, I, Sunderkoetter, C, Guenzel, J, Athanassiou, P, Dimitroulas, T, Settas, L, Kritikos, I, Tsifetaki, N, Garyfallos, A, Vasilopoulos, D, Boura, P, Kamali, S, Aslanidis, S, Vlachoyannopoulos, P, Galanopoulo, V, Sakkas, L, Koutroubas, A, Elezoglou, T, Galanopoulos, N, Grier, A, Murray, M, O'Rourke, M, Del Papa, N, Maglione, W, Zeni, S, Foti, R, Benenati, A, De Vita, S, Ferraccioli, G, Grassi, W, de Angeli, R, Pomponio, G, Mussi, A, Colonna, L, Airo, P, Zingarelli, S, Scorza, R, Serverino, A, Puppo, F, Negrini, S, Roma, I, Salsano, F, Triolo, G, Mazzuca, S, Carignola, R, Gatti, S, Lunardi, G, Riccieri, V, Salvarani, C, Bajocchi, G, Varcasia, G, Marasini, B, Belloll, L, de Luca, R, Stisi, S, Bellissimo, S, Fusaro, E, Pellerito, R, Cozzi, F, Rizzo, M, Bartoluzzi, A, Trotta, F, Cantatore, F, Corrado, A, Ferri, Claudio, Colaci, M, Malavolta, N, Mule, R, Galeazzi, M, Lapadula, G, Mathieu, A, Vacca, A, Giacomelli, Roberto, Cipriani, Paola, Montecucco, Cm, Codullo, V, Bucci, R, Battaglia, E, Valentini, G, Cuomo, G, Terlizzi, N, Serafino, L, Reumatologia, Uo, Bombardieri, S, Della Rossa, A, Doveri, M, Perricone, R, de Mattia, M, Pallotta, S, Groenendael, Jh, Seys, P, Goekoop, Rj, Han, Kh, Wlarvens, M, Bonte Mineur, F, de Bois MH, de Beus WM, van Zeben, D, Vonk, M, Knaapen, Hk, Smit, A, Bootsma, H, Ton, E, Voskuyl, A, Dutmer, Ea, Stalk, Jn, Madland, Tm, Seip, M, Hoffmann Vold AM, Bitter, H, Stocklund Thomsen, R, Resende, C, Ponte, C, Martinho, S, Silva, F, Ferreira, P, Grilo, A, Riso, N, Santos, C, Camara, I, Costa, J, Alves, J, Oliveira, S, Almeida, I, Silva, I, Cordeiro, A, Coelho, P, Lukac, J, Dolnicar, As, Espinosa, G, Mejia, Jc, Ramos, M, Plasin Rodriguez MA, Mera, A, Blanco, Js, Diaz, Jj, Losada, L, Perez, E, Maneiro, Jr, Caamano, M, Fermindez, S, Insua, Sa, Barbado, J, Fonseca, Em, Nufio, Fj, Castellvi, I, Garcia de Ia Pena, P, Bellido, D, Paulino, M, Garcia, Pv, Salas, V, Minguez, Md, Sanchez, Ma, Urrego, C, Martin, I, Rueda, A, Calvo, J, Ripoll, Mm, Torres, Mc, Corteguera, M, Maceiras, F, Cruz, J, Mosquera, Ja, Gomez, R, Area, B, Carrio, I, Rubio, M, Castellvi Barranco, I, Santos, P, Simeon, Cp, Fonollosa, V, Egurbide, Mv, Garcia de Vicuna, R, Vicente, E, Villaverde, V, Fernandez, C, Garcia, E, Uson, J, Miguelez, R, Callejas, Jl, Ortego, N, Roman, J, Alegre Sancho JJ, Robles, A, Rios, Jj, Bonilla, Mg, Sanchez Andrade, A, Vazquez, Tr, Miranda, Ja, Saez, L, Zea, A, De la Puente, C, Martinez, Fg, Aguirre, Ma, Collado, P, Cruz, A, Crespo, M, Sanchez Roman, J, Castillo, Mj, Garcia, Am, Muniz, G, Hedin, Pj, Stahl, C, Bracin, T, Nordin, A, Albertsson, K, Rydvald, Y, Thorsson, C, Hermansson, E, Maurer, B, Verner, D, Schmidt Bosshard, R, Hall, F, Murphy, K, Lamb, J, Anderson, M, Moots, R, Buch, M, Bissell, L, Madhok, R, Hampson, R, D'Cruz, D, Choong, Lm, Gordon, P, Dobson, J, Salerno, R, Nisar, M, Williams, C, Wilcox, L, Denton, C, Ochiel, R, Ngcozana, T, Parker, L, Vincent, R, Mchugh, N, Cole, S, Brown, S, James, J, Herrick, A, Manning, J, Moore, T, Faizal, A, Skyes, H, Smythe, A, and Hamilton, A.

Published
2013

47. There is a need for new systemic sclerosis subset criteria. A content analytic approach.

Author

Johnson, SR, Soowamber, ML, Fransen, J, Khanna, D, Van Den Hoogen, F, Baron, M, Matucci-Cerinic, M, Denton, CP, Medsger, TA, Carreira, PE, Riemekasten, G, Distler, J, Gabrielli, A, Steen, V, Chung, L, Silver, R, Varga, J, Müller-Ladner, U, Vonk, MC, and Walker, UA

Subjects
NOSOLOGY, SYSTEMIC scleroderma, AUTOANTIBODIES, MEDICAL communication, CLUSTER analysis (Statistics), PROGNOSIS, THERAPEUTICS, RISK assessment, CROSS-sectional method, DISEASE progression, DIAGNOSIS
Abstract

Objectives: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets.Methods: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed.Results: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly).Conclusions: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies). [ABSTRACT FROM AUTHOR]

Published
2018
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