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Abstract Number: 1699

Neutropenia After Rituximab in Rheumatoid Arthritis and Other Autoimmune Diseases Is a Rare Events : Date From the Autoimmunity and Rituximab Registry

Jean Hugues Salmon1, Patrice Cacoub2, Bernard G. Combe3, Jean Sibilia4, Beatrice Pallot Prades5, Olivier Fain6, Alain G. Cantagrel7, Maxime Dougados8, Olivier Meyer9, Philippe Carli10, Edouard Pertuiset11, Isabelle Pane12, Philippe Ravaud13, Xavier Mariette14 and Jacques-Eric Gottenberg15, 1Rheumatology, Reims, France, 2Internal Medicine, Assistance Publique-Hôpitaux de Paris, Hopital Pitié-Salpétrière, Paris, France, 3Rhumatologie, Hopital Lapeyronie, Montpellier, France, 4Rheumatology, CHU Hautepierre, Strasbourg, France, 5Rheumatology department, Saint Etienne university hospital, Saint Etienne, France, 6Internal Medicine, Jean Verdier Hospital, Bondy, France, 7Rheumatology, Place du Docteur Baylac, Toulouse, France, 8Rheumatology B Department, Paris-Descartes University, APHP, Cochin Hospital, Paris, France, 9Rheumatology, Hopital Bichat, Paris, France, 10HIA sainte Anne, Toulon, France, 11Rheumatology, Ch Rene Dubos, Pontoise, France, 12Hotel Dieu University Hospital Paris, Hotel Dieu University Hospital Paris, Paris, France, 13Epidemiology, Hopital Hotel Dieu, Paris Descartes University, Paris, France, 14Rheumatology, Université Paris-Sud, Le Kremlin Bicetre, France, 15Rheumatology, Strasbourg University Hospital, Strasbourg, France

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Auto-immunity, neutropenia, rheumatoid arthritis (RA) and rituximab

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Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy: Safety II

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Limited data are available regarding the proportion and severity of late onset neutropenia after RTX in large and unselected populations of patients with various autoimmune diseases. The largest series included 209 patients followed up to 1 year (162 patients with rheumatoid arthritis (RA) and 47 patients with other autoimmune diseases) and identified 11 RTX-induced neutropenia (5.2%) (Tesfa D, A&R 2011).

Methods:

The AutoImmunity and Rituximab registry (AIR) has included 2653 patients (2000 patients with RA including 1975 patients with at least 1 follow-up visit,  and 653 patients with AIDs, including 649 patients with at least 1 follow-up visit). Patients are prospectively followed up every 6 months for 5 years. For each neutropenia episode registered, the clinician in charge of the patient was asked to fill a specific questionnaire.

Results:

A neutropenia was confirmed by clinicians in 85 patients (48 RA and 37 AIDs (17 systemic lupus erythematosus, 12 vasculitis, 1 primary Sjögren’s syndrome, 1 myositis, and 6 other AIDs). In 35 patients, neutropenia resulted from other reasons than RTX (chronic autoimmune-disease related neutropenia, other drug-induced neutropenia, blood malignancies). RTX-induced neutropenia according to the clinician was observed in 50 patients (32 RA [1.6% of all patients with RA], 18 AIDs [2.8% of patients with AIDs]: 8 SLE, 7 vasculitis, 1 myositis, 2 other AIDs). 6 patients (12%) (1 RA, 5 AIDs) had neutrophils < 500/mm3, 9 (18%) (8 RA, 1 AIDs)had neutrophils between 500 and 1000/mm3 and 35 (70%) (23 RA and 12 AIDs)patients had neutrophils between 1000 and 1500/mm3.

RTX-induced neutropenia occurred after a median of 6.7  months in RA and 6.3 months in AIDs after the last infusion of  the 1st cycle (25 patients,50%), 2d cycle (16 patients, 32%), 3d cycle (2 patients, 4%), 4th  or subsequent cycle  ( 7 patients, 14%). 5 patients 1 RA, 2 SLE, 1 vasculitis and 1 other AID, 4 with neutrophils < 500/mm3, 1 between 500 and 1000/mm3) (5.9%) developed a non opportunistic serious infection (2 urinary and 1 bronchopulmonary infections, 12 isolated fevers) and required G-CSF injections, with a favorable outcome. 25 patients (50%) were retreated with RTX after resolution of their neutropenia and a new episode of neutropenia occurred in 8 of them.

Conclusion:

Late-onset neutropenia can occur after RTX and infrequently results in serious infections. One third of the patients with RTX-induced neutropenia recurred in case of realization of a new cycle of RTX. Thus, monitoring of white blood count should be performed after RTX. However, in this large registry of patients with autoimmune diseases, the frequency of RTX-induced neutropenia is much lower than that previously reported in patients treated with RTX for lymphoma.


Disclosure:

J. H. Salmon,
None;

P. Cacoub,
None;

B. G. Combe,
None;

J. Sibilia,
None;

B. Pallot Prades,
None;

O. Fain,
None;

A. G. Cantagrel,
None;

M. Dougados,
None;

O. Meyer,
None;

P. Carli,
None;

E. Pertuiset,
None;

I. Pane,
None;

P. Ravaud,
None;

X. Mariette,
None;

J. E. Gottenberg,
None.

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