Management of nonviral mixed cryoglobulinemia vasculitis refractory to rituximab: Data from a European collaborative study and review of the literature.


Journal

Autoimmunity reviews
ISSN: 1873-0183
Titre abrégé: Autoimmun Rev
Pays: Netherlands
ID NLM: 101128967

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 06 12 2021
accepted: 01 01 2022
pubmed: 8 1 2022
medline: 24 3 2022
entrez: 7 1 2022
Statut: ppublish

Résumé

Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients refractory to RTX are lacking. We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review. Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1-3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively. In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections.

Sections du résumé

BACKGROUND BACKGROUND
Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients refractory to RTX are lacking.
METHODS METHODS
We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review.
RESULTS RESULTS
Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1-3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively.
CONCLUSION CONCLUSIONS
In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections.

Identifiants

pubmed: 34995764
pii: S1568-9972(22)00004-0
doi: 10.1016/j.autrev.2022.103034
pii:
doi:

Substances chimiques

Rituximab 4F4X42SYQ6

Types de publication

Journal Article Multicenter Study Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

103034

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Auteurs

Clara Pouchelon (C)

Department of Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France.

Marcella Visentini (M)

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Giacomo Emmi (G)

Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

Véronique le Guern (V)

Department of Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France.

Luca Quartuccio (L)

Clinic of Rheumatology, Department of Medicine (DAME), ASUFC, University of Udine, Udine, Italy.

Maxime Samson (M)

Service de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Dijon, France.

Nils Venhoff (N)

Clinic for Rheumatology and Clinical Immunology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Antoine Briantais (A)

Department of Internal Medicine, CHU Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, Aix-Marseille Université, France.

Milvia Casato (M)

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Emmanuel Chatelus (E)

Centre National de Référence des Maladies Auto-Immunes et Systémiques Rares, Est/Sud-Ouest (RESO), France, Service de rhumatologie, Centre Hospitalier Universitaire de Strasbourg, 1 avenue Molière, 67098 Strasbourg, France.

Marie Chilles (M)

Department of Internal Medicine, Orléans, France.

Maria C Cid (MC)

Vasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Elisabeth Diot (E)

Service de Médecine Interne, CHRU Tours, Tours, France.

Mikael Ebbo (M)

Department of Internal Medicine, CHU Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, Aix-Marseille Université, France.

Stanislas Faguer (S)

Département de Néphrologie et Transplantation d'Organes, CHU de Toulouse, Toulouse, France.

Bernhard Hellmich (B)

Department of Internal Medicine, Rheumatology and Immunology, Medius Kliniken, University of Tübingen, Kirchheim-Teck, Germany.

Marie Jachiet (M)

Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris.

Thomas Moulinet (T)

Department of Internal Medicine and Clinical Immunology, Regional Competence Center for Rare and Systemic Autoimmune Disease, Nancy University Hospital, Vandœuvre-lès-Nancy, University of Lorraine, UMR 7365 CNRS, IMoPA, Vandœuvre-lès-Nancy, France.

François Perrin (F)

Department of Internal Medicine, Saint-Nazaire Hospital, France.

Thomas Quémeneur (T)

Département de Néphrologie and Département de Médecine Interne, Centre Hospitalier de Valenciennes, Valenciennes, France.

Renato Alberto Sinico (RA)

Department of Medicine and Surgery, University of Milano Bicocca, and Renal Unit, ASST-Monza, Milan/Monza, Italy.

Benjamin Terrier (B)

Department of Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris (AP-HP), Université de Paris, Paris, France. Electronic address: benjamin.terrier@aphp.fr.

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