title: Predictors of early relapse in patients with non-infectious mixed cryoglobulinemia vasculitis: results from the French nationwide CryoVas survey.
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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.affiliation: Department of Internal Medicine, CHU, Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marie
authors.affiliation: Department of Internal Medicine, CHRU Claude Huriez, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.affiliation: Department of Nephrology, CH Côte Basque, Bayonne, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Lacraz
authors.affiliation: Department of Internal Medicine, CHU, Marseille, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Belenotti
authors.affiliation: Department of Internal Medicine, CHU, Brest, France.
authors.forename: Luc
authors.initials: L
authors.lastname: de Saint-Martin
authors.affiliation: Department of Internal Medicine, CH, Valenciennes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quemeneur
authors.affiliation: Department of Nephrology, CHU, Toulouse, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Huart
authors.affiliation: Department of Internal Medicine, CHU, Bordeaux, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
authors.affiliation: Department of Internal Medicine, CHU, Clermont-Ferrand, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Le Guenno
authors.affiliation: Department of Internal Medicine, Hôpital Foch, Suresnes, France.
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Kahn
authors.affiliation: Department of Internal Medicine, CH, Mulhouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hinschberger
authors.affiliation: Department of Internal Medicine, CHU, Montpellier, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rullier
authors.affiliation: Department of Internal Medicine, CHU, Tours, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.affiliation: Department of Internal Medicine, CHU, Bordeaux, France.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.affiliation: Department of Nephrology, CHU, Poitiers, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
authors.affiliation: Department of Internal Medicine, CH, Valence, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Zénone
authors.affiliation: UMR-S707, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris 6, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.affiliation: Department of Hematology, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Department of Neurology, Groupe Hospitalier Pitié-Salpetrière, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Léger
authors.affiliation: Department of Rheumatology, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, Université Paris-Sud, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Department of Dermatology, Hôpital Tenon, Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Senet
authors.affiliation: Nephrology, Hôpital Tenon, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Plaisier
authors.affiliation: 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.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D003449:Cryoglobulinemia / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D012008:Recurrence; D012074:Remission Induction; D014657:Vasculitis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology
keywords: Mixed cryoglobulinemia; Relapse; Vasculitis