Arsene Mekinian1, Guillaume Dervin2, Nathanael Lapidus3, Jean-Emmanuel Kahn4, Louis Terriou5, Eric Liozon6, Eric Grignano2, Jean-Charles Piette7, Odile Beyne Rauzy8, Vincent Grobost9, Pascal Godmer10, Jerome Gillard11, Julien Rossignol12, David Launay5, Achille Aouba13, Thierry Cardon14, Laurence Bouillet15, Jonathan Broner16, Julien Vinit17, Lionel Ades18, Fabrice Carrat3, Clementine Salvado19, Eric Toussirot20, Mathilde Versini21, Nathalie Costedoat-Chalumeau22, Jean Baptiste Fraison22, Philippe Guilpain16, Pierre Fenaux18, Olivier Fain23. 1. Service de Médecine Interne, Hôpital Saint Antoine, APHP, Université Paris 6, 75012 Paris, France. Electronic address: arsene.mekinian@aphp.fr. 2. Service de Médecine Interne, Hôpital Saint Antoine, APHP, Université Paris 6, 75012 Paris, France. 3. Service de Biostatistiques, Hôpital Saint Antoine, APHP, Université Paris 6, 75012 Paris, France. 4. Service de médecine interne, Université Versailles-Saint Quentin en Yvelines, Hôpital Foch, Suresnes, France. 5. Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), 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. 6. Service de médecine interne, CHU Dupuytren, Limoges, France. 7. Service de médecine interne, Hôpital Pitié Salpetrière, APHP, Université Paris 6, Paris, France. 8. Service de médecine interne, CHU de Purpan Toulouse, France. 9. Service de médecine interne, CHU Clermont Ferrand, Clermont Ferrand, France. 10. Service de médecine interne, CHU Bretagnes Atlantique, Vannes, France. 11. Service de médecine interne, Centre hospitalier Lons le Saunier, 39016, France. 12. Service hématologie, Hôpital Necker Enfant Malades, Université Paris 5, Paris, France. 13. Service de médecine interne, Hôpital Caen, Caen, France. 14. Service de Rhumatologie, CHU Lille, Lille, France. 15. Service de médecine interne, CHU Grenoble, Grenoble, France. 16. Service de médecine interne, Hôpital Saint Eloi, Université de Montpellier, France. 17. Service de médecine interne, CHU Chalon sur Saône, 71321 Chalon, France. 18. Service d'hématologie clinique, CHU Avicenne, Bobigny, France. 19. Service hématologie, Hôpital Henri Mondor, Créteil, France. 20. INSERM CIC 1431 Clinical Investigation Center in Biotherapy and Department of Rheumatology, University hospital Besançon, France. 21. Service de médecine interne, CHU Nice, Nice, France. 22. AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France; INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France. 23. Service de Médecine Interne, Hôpital Saint Antoine, APHP, Université Paris 6, 75012 Paris, France; Service de médecine interne, CHU Bretagnes Atlantique, Vannes, France.
Abstract
BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. METHODS: In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics. RESULTS: We included 29 patients (median age 67years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection. CONCLUSION: This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.
BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. METHODS: In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics. RESULTS: We included 29 patients (median age 67years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection. CONCLUSION: This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.