Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry

Authors

  • J.-E. Gottenberg,

    Corresponding author
    1. Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, Strasbourg, France
    • Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, 1 Avenue Molière, 67000 Strasbourg, France
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    • Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • P. Ravaud,

    1. Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, and Université Denis Diderot, INSERM U738, Paris, France
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    • Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • T. Bardin,

    1. Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France
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    • Dr. Bardin has received consulting fees, speaking fees, and/or honoraria from Ipsen, Menarini, Roche, Wyeth, and Bristol-Myers Squibb (less than $10,000 each).

  • P. Cacoub,

    1. Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
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    • Dr. Cacoub has received consulting fees, speaking fees, and/or honoraria from Servier, Vifor Pharma, and Schering-Plough (more than $10,000 each).

  • A. Cantagrel,

    1. Hôpital Purpan and Université Paul Sabatier, Toulouse, France
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    • Dr. Cantagrel has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • B. Combe,

    1. Hôpital Lapeyronie and Université Montpellier I, UMR5535, Montpellier, France
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    • Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • M. Dougados,

    1. Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, and Université Paris-Descartes, UPRES-EA 4058, Paris, France
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    • Dr. Dougados has received consulting fees, speaking fees, and/or honoraria from Roche, Abbott, and Bristol-Myers Squibb (more than $10,000 each).

  • R. M. Flipo,

    1. Centre Hospitalier Régional Universitaire de Lille and Université de Lille-2, Lille, France
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  • B. Godeau,

    1. Centre Hospitalier Universitaire Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, and Université Paris 12, Créteil, France
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    • Dr. Godeau has received consulting fees, speaking fees, and/or honoraria from Roche, Amgen, GlaxoSmithKline, and LFB Biotechnologies (less than $10,000 each).

  • L. Guillevin,

    1. Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
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    • Dr. Guillevin has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • X. Le Loët,

    1. Centre Hospitalier Universitaire de Rouen and INSERM U905, Rouen, France
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    • Dr. Le Loët has received consulting fees, speaking fees, and/or honoraria from Abbott, Roche, Roche-Chugai, Schering-Plough, and Wyeth (less than $10,000 each).

  • E. Hachulla,

    1. Hôpital Claude Huriez and Université de Lille, Lille, France
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    • Dr. Hachulla has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • T. Schaeverbeke,

    1. Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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    • Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  • J. Sibilia,

    1. Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, Strasbourg, France
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    • Dr. Sibilia has received consulting fees, speaking fees, and/or honoraria from Wyeth, Abbott, Schering-Plough, Pfizer, Merck, UCB, Actelion, Roche, and Bristol-Myers Squibb (less than $10,000 each).

  • G. Baron,

    1. Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, and Université Denis Diderot, INSERM U738, Paris, France
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  • X. Mariette

    Corresponding author
    1. Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, INSERM U802, and Université Paris-Sud 11, Le Kremlin Bicêtre, France
    • Service de Rhumatologie, Hôpital de Bicêtre, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France
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    • Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).


Abstract

Objective

The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry.

Methods

The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed.

Results

Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3–7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3–6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6–15.2], P = 0.005) were significantly associated with increased risk of a severe infection.

Conclusion

The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.

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