Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry

J H Salmon; P Cacoub; B Combe; J Sibilia; B Pallot-Prades; O Fain; A Cantagrel; M Dougados; E Andres; O Meyer; P Carli; E Pertuiset; I Pane; F Maurier; P Ravaud; X Mariette; J E Gottenberg

doi:10.1136/rmdopen-2014-000034

Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry

RMD Open. 2015 Jun 30;1(1):e000034. doi: 10.1136/rmdopen-2014-000034. eCollection 2015.

Authors

J H Salmon¹, P Cacoub², B Combe³, J Sibilia⁴, B Pallot-Prades⁵, O Fain⁶, A Cantagrel⁷, M Dougados⁸, E Andres⁹, O Meyer¹⁰, P Carli¹¹, E Pertuiset¹², I Pane¹³, F Maurier¹⁴, P Ravaud¹³, X Mariette¹⁵, J E Gottenberg¹⁶

Affiliations

¹ Rheumatology Department, CHU Reims, Reims, France.
² Departement Hospitalo-Universitaire I2B, UPMC Univ Paris 06, CNRS, UMR 7211, INSERM, UMR_S 959, Department of Internal Medicine, Groupe Hospitalier Pitié-Salpêtrière (AP-HP), Paris, France.
³ Rheumatology Department, Lapeyronie University Hospital, Montpellier I, University, UMR5535, Montpellier, France.
⁴ Rheumatology department, National Center for Rare Systemic Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, INSERM UMRS_1109, Université de Strasbourg, Strasbourg, France.
⁵ Rheumatology Department, CHU Saint-Etienne, Saint-Etienne, France.
⁶ Department of Internal Medicine, Hôpital Jean Verdier, Bondy, France.
⁷ Rheumatology Center, Purpan Hospital, Paul Sabatier University, Toulouse, France.
⁸ Medicine Faculty, Paris-Descartes University, Paris, UPRES-EA 4058, Cochin Hospital, Rheumatology B, Paris, France.
⁹ Department of Internal Medicine, University Hospital of Strasbourg, Strasbourg, France.
¹⁰ Rheumatology Department, GroupeHospitalier Bichat-Claude Bernard (AP-HP), Paris, France.
¹¹ Department of Internal Medicine, Hôpital D'Instruction des Armeés Sainte-541 Anne, Toulon, France.
¹² Rheumatology Department, CH René Dubos, Pontoise, France.
¹³ Centre de Recherche en Epidémiologie et Statistiques, INSERM U1153, Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris (AP-HP), Descartes University, Paris, France.
¹⁴ Department of Internal Medicine, CHR Metz, Metz, France.
¹⁵ Rheumatology Department, Hôpitaux Universitaires Paris-Sud, AP-HP, INSERM U1184, IMVA: Center of Immunology of Viral Infections and Autoimmune Diseases, Paris, France.
¹⁶ Rheumatology Department, National Center for Rare Systemic Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Université de Strasbourg, Strasbourg, France.

Abstract

Objectives: To evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry.

Methods: The AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient.

Results: Among 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1.3% of patients with RA, 0.6/100 patient-years), and AIDs in 15 (2.3% of patients with AIDs, 1.5/100 patient-years)). 6 patients (15%) had neutrophils <500/mm(3), 8 (20%) had neutrophils between 500 and 1000/mm(3), and 26 (65%) had neutrophils between 1000 and 1500/mm(3). Neutropenia occurred after a median period of 4.5 (3-6.5) months after the last RTX infusion in patients with RA, and 5 (3-6.5) months in patients with AIDs. 5 patients (12.5%), 4 of them with neutrophils lower than 500/mm(3), developed a non-opportunistic serious infection and required antibiotics and granulocyte colony-stimulating factor injections, with a favourable outcome. After resolution of their RTX-related neutropenia, 19 patients (47.5%) were re-treated, and neutropenia reoccurred in 3 of them.

Conclusions: Late-onset neutropenia might occur after RTX and may result in serious infections. Thus, monitoring of white cell count should be performed after RTX. However, in this large registry of patients with AIDs, the frequency of RTX-induced neutropenia was much lower than that previously reported in patients treated for blood malignancies or AIDs.

Keywords: Autoimmune Diseases; Rheumatoid Arthritis; Treatment.