1641 - Low Serum IgG Level After Rituximab Is Associated with An Increased Risk of Serious Infections in Rheumatoid Arthritis: Data of the AIR Registry

Monday, November 7, 2011: 2:30 PM
W375c (McCormick Place West)
Jacques-Eric Gottenberg1, Philippe Ravaud2, Thomas Bardin3, Patrice Cacoub4, Alain G. Cantagrel5, Bernard G. Combe6, Maxime Dougados7, Rene-Marc Flipo8, Bertrand Godeau9, Loic Guillevin10, Xavier X. Le Loet11, Eric Hachulla12, Thierry Schaeverbeke13, Jean Sibilia14, Isabelle Pane15, Adelina Abbe15, Gabriel Baron16 and Xavier Mariette17, 1Strasbourg University Hospital, Strasbourg, France, 2Hotel Dieu University hospital, France, 3Service de Rhumatologie. Centre Viggo Petersen. Hôpital Lariboisiere, Paris, France, 4CHU Pitié-Salpêtrière, Paris, France, 5Hopital Purpan, Toulouse CEDEX 9, France, 6Hopital Lapeyronie, Montpellier, France, 7Paris-Descartes University, Cochin Hospital, Paris, France, 8Hopital R Salengro CHRU, Lille CEDEX, France, 9Service de médecine interne, Université Paris Est Créteil, AP-HP, Hôpital Mondor Créteil, France, Creteil, France, 10Cochin University Hospital, Paris, France, 11CHU de ROUEN, Rouen CEDEX, France, 12Internal Medicine, Lille CEDEX, France, 13Pellegrin Hospital, Bordeaux, France, 14Service de rhumatologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Strasbourg, France, 15France, 16Epidemiology, Paris, France, 17Université Paris-Sud, Le Kremlin Bicetre, France
Presentation Number: 1641


Rituximab (RTX) might result in decreased serum immunoglobulin levels, in a proportion of patients with rheumatoid arthritis (RA) increasing with the number of RTX cycles. Very limited real life data are available regarding the risk of serious infections in patients who develop hypogammaglobulinemia after RTX. The present study aimed to investigate the association between low gammaglobulin levels after RTX and the occurrence of serious infections.


The 5-year prospective and multicenter AIR registry has been set up by the French Society of Rheumatology in 2006. Serious adverse events, including serious infections (which require either hospitalization or intravenous antibiotics) are validated by two investigators using chart copies. 


Among the 2000 patients with RA included in the AIR registry, gammaglobulin, IgM or IgG after RTX levels were collected in 1146 (57.3%), 1148 (57.4%) and 1150 (57.5%) patients, respectively. Low levels after RTX (gammaglobulins <6g/l, IgM<0.5g/l, or IgG<6g/l) were observed in 178 (15.5%), 306 (26.6%), and 139 (12.1%) patients.  Serious infections occurred in 24 patients (13.5%) with a low gammaglobulin level after RTX and in 85 (8.8%) patients with a normal gammaglobulin level, resulting in 6.3 vs 4.6 serious infections / 100 patient/years (4.9 serious infections /100 patient/years in the whole population who had a gammaglobulin assessment after RTX). Serious infections occurred in 36 (11.8%) patients with a low IgM level and in 68 (8.1%) patients with a normal IgM level, resulting in 5.5 vs 4.3 serious infections / 100 patient/years (4.7 in all patients with IgM assessment after RTX). Serious infections occurred in 21 patients (15.1%) with a low IgG level and in 83 (8.2%) patients with a normal IgG level, resulting in 10.0 vs 3.8 serious infections / 100 patient/years (6.2 serious infections/100 patient/years in all patients with IgG assessment after RTX). In univariate analysis adjusted on follow-up duration, only low IgG after RTX was associated with an increased risk of serious infections(OR 1.99 95% CI [1.2-3.3], P= 0.008), but not low gammaglobulin (OR 1.5 95% CI [0.9-2.5], P= 0.09) or low IgM level (OR 1.5 95% CI [0.9-2.3], P= 0.08). Preliminary results showed that hypoIgG after RTX was associated with an older age, history of cancer or of serious or recurrent infections. In multivariate analysis taking into account these latter parameters, low IgG after RTX remained associated with the risk of serious infections.


Converse to low gammaglobulin or low IgM level, low IgG after RTX is associated with a significant increase in the risk of serious infections in common practice. This had not been reported in long term extension phases of controlled trials, maybe due to the limited comorbidities of patients included. These results confirm that serum IgG level should be checked after RTX and the benefice/risk balance of retreatment with RTX discussed for each patient with low IgG level after RTX.

Keywords: immunoglobulin (IG), rheumatoid arthritis, treatment and rituximab

Disclosure: J. E. Gottenberg, None; P. Ravaud, None; T. Bardin, Savient Pharmaceutiicals, Inc., 5 ; P. Cacoub, None; A. G. Cantagrel, None; B. G. Combe, None; M. Dougados, Abbott Immunology Pharmaceuticals, 5, Pfizer Inc, 5, sanofi aventis, 2, Abbott Immunology Pharmaceuticals, 2, Pfizer Inc, 2 ; R. M. Flipo, None; B. Godeau, None; L. Guillevin, None; X. X. Le Loet, None; E. Hachulla, None; T. Schaeverbeke, Pfizer, Roche, Abbott, 5 ; J. Sibilia, None; I. Pane, None; A. Abbe, None; G. Baron, None; X. Mariette, Pfizer Inc, 2, Roche Pharmaceuticals, 2, GlaxoSmithKline, 5, Pfizer Inc, 5, Roche Pharmaceuticals, 5, UCB, 5 .