Rheumatoid Arthritis Clinical Studies

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

  1. J.-E. Gottenberg1,†,*,
  2. P. Ravaud2,†,
  3. T. Bardin3,‡,
  4. P. Cacoub4,§,
  5. A. Cantagrel5,¶,
  6. B. Combe6,†,
  7. M. Dougados7,‖,
  8. R. M. Flipo8,
  9. B. Godeau9,††,
  10. L. Guillevin10,‡‡,
  11. X. Le Loët11,§§,
  12. E. Hachulla12,¶¶,
  13. T. Schaeverbeke13,†,
  14. J. Sibilia1,‖‖,
  15. G. Baron2,
  16. X. Mariette14,†,*

Article first published online: 6 MAY 2010

DOI: 10.1002/art.27555

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 62, Issue 9, pages 2625–2632, September 2010

Additional Information

How to Cite

Gottenberg, J.-E., Ravaud, P., Bardin, T., Cacoub, P., Cantagrel, A., Combe, B., Dougados, M., Flipo, R. M., Godeau, B., Guillevin, L., Loët, X. L., Hachulla, E., Schaeverbeke, T., Sibilia, J., Baron, G. and Mariette, X. (2010), Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry. Arthritis & Rheumatism, 62: 2625–2632. doi: 10.1002/art.27555

Author Information

  1. 1

    Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, Strasbourg, France

  2. 2

    Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, and Université Denis Diderot, INSERM U738, Paris, France

  3. 3

    Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France

  4. 4

    Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

  5. 5

    Hôpital Purpan and Université Paul Sabatier, Toulouse, France

  6. 6

    Hôpital Lapeyronie and Université Montpellier I, UMR5535, Montpellier, France

  7. 7

    Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, and Université Paris-Descartes, UPRES-EA 4058, Paris, France

  8. 8

    Centre Hospitalier Régional Universitaire de Lille and Université de Lille-2, Lille, France

  9. 9

    Centre Hospitalier Universitaire Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, and Université Paris 12, Créteil, France

  10. 10

    Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

  11. 11

    Centre Hospitalier Universitaire de Rouen and INSERM U905, Rouen, France

  12. 12

    Hôpital Claude Huriez and Université de Lille, Lille, France

  13. 13

    Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

  14. 14

    Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, INSERM U802, and Université Paris-Sud 11, Le Kremlin Bicêtre, France

  1. †

    Drs. Gottenberg, Ravaud, Combe, Schaeverbeke, and Mariette have received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  2. ‡

    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).

  3. §

    Dr. Cacoub has received consulting fees, speaking fees, and/or honoraria from Servier, Vifor Pharma, and Schering-Plough (more than $10,000 each).

  4. Dr. Cantagrel has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  5. ‖

    Dr. Dougados has received consulting fees, speaking fees, and/or honoraria from Roche, Abbott, and Bristol-Myers Squibb (more than $10,000 each).

  6. ††

    Dr. Godeau has received consulting fees, speaking fees, and/or honoraria from Roche, Amgen, GlaxoSmithKline, and LFB Biotechnologies (less than $10,000 each).

  7. ‡‡

    Dr. Guillevin has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  8. §§

    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).

  9. ¶¶

    Dr. Hachulla has received consulting fees, speaking fees, and/or honoraria from Roche (less than $10,000).

  10. ‖‖

    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).

*Service de Rhumatologie, Hôpitaux Universitaires de Strasbourg, 1 Avenue Molière, 67000 Strasbourg, France

Publication History

  1. Issue published online: 31 AUG 2010
  2. Article first published online: 6 MAY 2010
  3. Manuscript Accepted: 29 APR 2010
  4. Manuscript Received: 10 DEC 2009

Funded by

  • Roche (an unrestricted educational grant)

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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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