Sébastien Sanges1, Sébastien Rivière2, Arsène Mekinian2, Thierry Martin3, Alain Le Quellec4, Emmanuel Chatelus5, Alain Lescoat6, Patrick Jego6, Claire Cazalets6, Thomas Quéméneur7, Noémie Le Gouellec7, Patricia Senet8, Camille Francès8, Alban Deroux9, Bernard Imbert9, Olivier Fain2, Latifatou Boukari10, Thomas Sené11, Christophe Deligny12, Alexis Mathian13, Christian Agard14, Grégory Pugnet15, Silvia Speca16, Sylvain Dubucquoi16, Pierre-Yves Hatron17, Éric Hachulla1, David Launay18. 1. Univ. Lille, INSERM U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France; INSERM, U995, F-59000 Lille, France; CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET). 2. AP-HP, Hôpital Saint Antoine, Service de Médecine Interne, Paris, France; UPMC Université Paris 06, Faculté de Médecine Pierre et Marie Curie, Paris, France. 3. Service d'Immunologie Clinique, Hôpitaux universitaires de Strasbourg, UPR CNRS 3572, Strasbourg, France. 4. Service de Médecine Interne et Maladies Multi-Organiques de l'Adulte, Hôpital Saint-Éloi, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France. 5. Hôpitaux Universitaires de Strasbourg, CHU Hautepierre, Service de Rhumatologie, Centre de Référence des Maladies Auto-Immunes Systémiques Rares, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, INSERM UMR 1109, Strasbourg, France. 6. Service de Médecine Interne, Centre Hospitalo-Universitaire de Rennes, Université de Rennes 1, Rennes, France. 7. Service de Médecine Interne, Néphrologie et Médecine Vasculaire, Centre Hospitalier de Valenciennes, Valenciennes, France. 8. Service de Dermatologie, Hôpital Tenon, AP-HP, UPMC, Paris, France. 9. Service de Médecine Interne, Université Grenoble Alpes, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France. 10. Service de Médecine Interne, Hôpital Jean-Verdier, AP-HP, Université Paris-13, Bondy, France. 11. Service de Médecine Interne et Rhumatologie, GH Diaconesses Croix Saint Simon, Paris, France. 12. Service de Médecine Interne et Rhumatologie 3C/5D, Centre Hospitalier Universitaire Pierre Zobda-Quitman, Fort-de-France, Martinique. 13. Service de Médecine Interne 2, Centre de Référence National pour le Lupus et le Syndrome des Antiphospholipides, institut E3M, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France; Sorbonne universités, UPMC université Paris 06, 75013 Paris, France. 14. Service de Médecine interne, Hôtel-Dieu, CHU de Nantes, Université de Nantes, Nantes, France. 15. CHU, Université de Toulouse, Faculté de Médecine, Service de Médecine Interne, Toulouse, France; INSERM, UMR 1027, Toulouse, France. 16. Univ. Lille, INSERM U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France; INSERM, U995, F-59000 Lille, France. 17. Univ. Lille, INSERM U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France; CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET). 18. Univ. Lille, INSERM U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France; INSERM, U995, F-59000 Lille, France; CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET). Electronic address: david.launay@univ-lille2.fr.
Abstract
BACKGROUND: As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS: 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS: We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION: Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.
BACKGROUND: As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS: 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS: We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION: Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.