Benjamin Terrier1, Isabelle Marie2, David Launay3, Adeline Lacraz4, Pauline Belenotti5, Luc de Saint-Martin6, Thomas Quemeneur7, Antoine Huart8, Fabrice Bonnet9, Guillaume Le Guenno10, Jean-Emmanuel Kahn11, Olivier Hinschberger12, Patricia Rullier13, Elisabeth Diot14, Estibaliz Lazaro9, Frank Bridoux15, Thierry Zénone16, Fabrice Carrat17, Olivier Hermine18, Jean-Marc Léger19, Xavier Mariette20, Patricia Senet21, Emmanuelle Plaisier22, Patrice Cacoub23. 1. Department of Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris (AP-HP), Université Pierre Descartes, Paris 5, Paris, France. 2. Department of Internal Medicine, CHU, Rouen, France. 3. Department of Internal Medicine, CHRU Claude Huriez, Lille, France. 4. Department of Nephrology, CH Côte Basque, Bayonne, France. 5. Department of Internal Medicine, CHU, Marseille, France. 6. Department of Internal Medicine, CHU, Brest, France. 7. Department of Internal Medicine, CH, Valenciennes, France. 8. Department of Nephrology, CHU, Toulouse, France. 9. Department of Internal Medicine, CHU, Bordeaux, France. 10. Department of Internal Medicine, CHU, Clermont-Ferrand, France. 11. Department of Internal Medicine, Hôpital Foch, Suresnes, France. 12. Department of Internal Medicine, CH, Mulhouse, France. 13. Department of Internal Medicine, CHU, Montpellier, France. 14. Department of Internal Medicine, CHU, Tours, France. 15. Department of Nephrology, CHU, Poitiers, France. 16. Department of Internal Medicine, CH, Valence, France. 17. UMR-S707, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris 6, Paris, France. 18. Department of Hematology, Hôpital Necker-Enfants Malades, Paris, France. 19. Department of Neurology, Groupe Hospitalier Pitié-Salpetrière, Paris, France. 20. Department of Rheumatology, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, Université Paris-Sud, France. 21. Department of Dermatology, Hôpital Tenon, Paris, France. 22. Nephrology, Hôpital Tenon, Paris, France. 23. Department of Internal Medicine, Reference Center for Autoimmune Diseases, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris 6, UMR 7211, F-75005 Paris, France; INSERM, UMR S 959, F-75013 Paris, France; CNRS, UMR 7211, F-75005 Paris, France; Departement Hospitalo-Universitaire I2B, Univ Paris 06, UMR 7211, F-75005, Paris, France; AP-HP, Groupe Hoitalier Pitié-Salpérière, Departement of Internal Médicine, 75013, Paris, France. Electronic address: patrice.cacoub@gmail.com.
Abstract
OBJECTIVE: Although in most patients induction therapy leads to complete or partial remission, relapses in patients with non-infectious mixed cryoglobulinemia vasculitis (CryoVas) remain a major problem. We aimed to identify predictors of early relapses occurring within the first 12months of treatment in such patients. METHODS: Patients included in the French CryoVas survey exhibiting complete/partial clinical remission and followed-up for at least 12months after induction therapy (n=145) were analyzed for predictors of early relapses. RESULTS: Forty out of 145 patients (28%) experienced early relapse. Relapses occurred after a median time of 9.5months after induction therapy (3-12) and involved skin (75%), joints and peripheral nerve (28% each), kidneys (25%) and gastrointestinal tract (5%). Baseline factors associated with an early relapse were purpura [HR 3.35 (1.02-10.97), P=0.046], cutaneous necrosis [HR 4.46 (1.58-12.57), P=0.005] and articular involvement [HR 2.20 (1.00-4.78), P=0.048]. The only factor negatively associated with an early relapse during follow-up was the achievement of complete immunological response [HR 0.07 (0.01-0.51), P=0.009]. The use of corticosteroids plus rituximab or cyclophosphamide tended to be associated negatively with early relapse [HR 0.43 (0.17-1.08), P=0.07]. CONCLUSION: In patients with non-infectious CryoVas, main predictors of early relapses after initial remission are purpura, articular involvement, and cutaneous necrosis. The absence of complete immunological response during follow-up was associated with early relapse. These findings may help in adapting future treatment strategies.
OBJECTIVE: Although in most patients induction therapy leads to complete or partial remission, relapses in patients with non-infectious mixed cryoglobulinemia vasculitis (CryoVas) remain a major problem. We aimed to identify predictors of early relapses occurring within the first 12months of treatment in such patients. METHODS:Patients included in the French CryoVas survey exhibiting complete/partial clinical remission and followed-up for at least 12months after induction therapy (n=145) were analyzed for predictors of early relapses. RESULTS: Forty out of 145 patients (28%) experienced early relapse. Relapses occurred after a median time of 9.5months after induction therapy (3-12) and involved skin (75%), joints and peripheral nerve (28% each), kidneys (25%) and gastrointestinal tract (5%). Baseline factors associated with an early relapse were purpura [HR 3.35 (1.02-10.97), P=0.046], cutaneous necrosis [HR 4.46 (1.58-12.57), P=0.005] and articular involvement [HR 2.20 (1.00-4.78), P=0.048]. The only factor negatively associated with an early relapse during follow-up was the achievement of complete immunological response [HR 0.07 (0.01-0.51), P=0.009]. The use of corticosteroids plus rituximab or cyclophosphamide tended to be associated negatively with early relapse [HR 0.43 (0.17-1.08), P=0.07]. CONCLUSION: In patients with non-infectious CryoVas, main predictors of early relapses after initial remission are purpura, articular involvement, and cutaneous necrosis. The absence of complete immunological response during follow-up was associated with early relapse. These findings may help in adapting future treatment strategies.