Infections in patients with rheumatoid arthritis treated with biologic agents.
OBJECTIVE
To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment.


METHODS
Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics.


RESULTS
Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls.


CONCLUSIONS
Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.
Listing
Joachim
J
German Rheumatism Research Centre, Schumannstrasse 21/22, D-10117 Berlin, Germany. Listing@drfz.de
Strangfeld
Anja
A
Kary
Sonja
S
Rau
Rolf
R
von Hinueber
Ulrich
U
Stoyanova-Scholz
Maria
M
Gromnica-Ihle
Erika
E
Antoni
Christian
C
Herzer
Peter
P
Kekow
Jörn
J
Schneider
Matthias
M
Zink
Angela
A
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D001688:Biological Products / Q000009:adverse effects*; D000068800:Etanercept; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D007239:Infections / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D012042:Registries; D012795:Sialoglycoproteins / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; C507763:IL1RN protein, human; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept