title: Update of EULAR recommendations for the treatment of systemic sclerosis.
abstract: The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
authors.affiliation: Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.affiliation: Rheumatology A Department, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Avouac
authors.affiliation: University Hospital Charité, Berlin, Germany.|University Hospital Zurich, Zurich, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Becker
authors.affiliation: Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kulak
authors.affiliation: Rheumatology A Department, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: University Hospital Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Clements
authors.affiliation: Research Laboratories and Clinical Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino, Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Department of Rheumatology and Immunology, Medical Center, University of Pecs, Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Czirjak
authors.affiliation: University of Belgrade, Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Del Galdo
authors.affiliation: University College London, London, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.affiliation: University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Jörg H W
authors.initials: JHW
authors.lastname: Distler
authors.affiliation: Hamburg Centre for Pediatric and Adolescence Rheumatology, Hamburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: FESCA, London, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Figelstone
authors.affiliation: University of Giessen, Bad Nauheim, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Frerix
authors.affiliation: University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: University of Florence, Florence, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.affiliation: University of Cologne, Cologne, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hunzelmann
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.affiliation: University of Florence, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Ariane L
authors.initials: AL
authors.lastname: Herrick
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van den Hoogen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: University of Lübeck, Lübeck, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Silver
authors.affiliation: Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Smith
authors.affiliation: Research Laboratories and Clinical Division of Rheumatology, Department of Internal Medicine, University of Genova, IRCCS AOU San Martino, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
authors.affiliation: University of Giessen, Bad Nauheim, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Tarner
authors.affiliation: Basel University, Basel, Switzerland.
authors.forename: Alan
authors.initials: A
authors.lastname: Tyndall
authors.affiliation: FESCA Patient Research Partner, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Welling
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Wigley
authors.affiliation: Second University of Naples, Naples, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Valentini
authors.affiliation: Basel University, Basel, Switzerland.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
authors.affiliation: University of Padua, Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Zulian
authors.affiliation: University of Giessen, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003697:Delphi Technique; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D005060:Europe; D005385:Fingers; D005473:Fluoxetine / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000628:therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000628:therapy*; D007674:Kidney Diseases / Q000209:etiology / Q000628:therapy*; D008171:Lung Diseases / Q000209:etiology / Q000628:therapy; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D044062:Prostaglandins I / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011928:Raynaud Disease / Q000209:etiology / Q000628:therapy*; D012219:Rheumatology; D012595:Scleroderma, Systemic / Q000150:complications / Q000628:therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D014456:Ulcer / Q000209:etiology / Q000628:therapy*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D005473:Fluoxetine; D005938:Glucocorticoids; D058986:Phosphodiesterase 5 Inhibitors; D044062:Prostaglandins I; D011720:Pyrazoles; D011743:Pyrimidines; D017367:Selective Serotonin Reuptake Inhibitors; C542595:riociguat
keywords: Cyclophosphamide; Methotrexate; Systemic Sclerosis; Treatment