Case reportSevere pyogenic infections in patients taking infliximab: A regional cohort study
Introduction
Infliximab has considerably benefited the management of patients with rheumatoid arthritis (RA) [1], [2], [3] and, more recently, with ankylosing spondylitis (AS) [4], [5], [6], [7]. Despite a good safety profile [8], [9], infliximab can induce side effects, which include infections [10], [11]. Published data have alerted clinicians to the risk of opportunistic infections and mycobacterial infections [12], [13]. Patient selection strategies designed to prevent these infections have been suggested [14].
Pyogenic infections have been reported also [15], [16], [17], [18]. Although minor in most instances, pyogenic infections can be life-threatening. There is no proof that the risk of severe pyogenic infections is increased by infliximab therapy. Neither is there any firm evidence that pyogenic infections in patients taking infliximab therapy are more severe or occur in association with specific patient-related factors. This probably explains why the preventive strategies suggested to date (e.g., pneumococcus immunization [19]) are less well standardized than those for tuberculosis. Thus, the recently published conclusions of a consensus conference merely indicate that infliximab therapy should not be started, or should be discontinued, in patients with severe infections such as septic arthritis, osteomyelitis, acute abscesses, infection of a prosthesis, sepsis, etc. [20]. According to the Summary of Product Characteristics, infliximab is “contraindicated in patients with severe infection such as sepsis, abscesses, tuberculosis, and opportunistic infections” and “should be discontinued if severe infection or sepsis develops”. The recommendations issued by the British Society for Rheumatology are somewhat more detailed [21], as they list among the contraindications to infliximab therapy the presence of risk factors for infection, such as chronic leg ulcer, a history within the last year of septic arthritis or infection of a prosthesis, a history of infection of a prosthesis at any time without removal of the implant, and a history of recurrent or relapsing lower respiratory tract infections.
Thus, large gaps exist in the currently available data on severe pyogenic infections in patients taking infliximab. In particular, little is known about risk factors. Recommendations for preventing these infections are often vague. The media have given less attention to pyogenic infections than to tuberculosis. Thus, when evaluating the risk/benefit ratio of infliximab therapy in potential candidates for this drug, clinicians may give greater weight to tuberculosis than to pyogenic infections.
Shortly, after infliximab was introduced on the market in France, a hospital network (the Bourgogne Infliximab Network) was set up in the Bourgogne region with the objective of collecting standardized follow-up data on all patients taking infliximab. Although risk factors for pyogenic infections are not listed on the data collection form, the available information may help to clarify the potential link between infliximab therapy and severe pyogenic infections. Indeed, the network has many strong points: multiple centers in the Bourgogne region include all patients given infliximab for RA or AS, data collection is highly standardized, and the patients are studied under the conditions of everyday clinical practice. Consequently, we evaluated the prevalence of severe pyogenic infections in the cohort and sought to identify risk factors.
Section snippets
Methods
All patients given infliximab for RA or AS in centers participating in the Bourgogne Infliximab Network were included prospectively in the cohort. The network includes all nine hospital departments in Bourgogne where one or more rheumatologists work either full time or part time (Auxerre, Avallon, Chalon sur Sâone, Dijon, Le Creusot, Mâcon, Montceau les Mines, Nevers, and Sens). The main objective of the network is to standardize the management and follow up of RA and AS patients given
Results
Eight of the nine centers in the Bourgogne Infliximab Network accepted to participate in the study. During the study period, 83 patients (55 women and 28 men with a mean age of 53.9 ± 13 years) were given infliximab to treat RA (60 patients including 48 women and 12 men with a mean age of 57.2 ± 13 years) or AS (23 patients including eight women and 15 men with a mean age of 45.5 ± 10 years). The mean oral glucocorticoid dosage at infliximab initiation was 9.3 ± 7 mg prednisone-equivalent in RA
Discussion
The prevalence of severe pyogenic infections was 6% in our cohort of patients given infliximab therapy for chronic inflammatory joint disease. At least one risk factor was present in every case.
Although some of our study data were collected prospectively, others were obtained by retrospective medical record review. This is the main weakness of our study. Because the retrospectively collected variables were not available for the entire cohort, we were unable to compare them in the groups with
Acknowledgments
We are grateful to the other physicians participating in the Bourgogne Infliximab Network: C. Bressot, A. Cherasse, J.A. Dellas, J. Dupuis, M. Falconnet, L. Julien, F. Marchand, N. Richard, and C. Sidot.
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