Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: comparison of adalimumab, etanercept and infliximab in the GISEA registry.
OBJECTIVE
To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register.


METHODS
The study involved 2769 adult patients with long-standing RA (mean age 53.2±13.4 years; mean disease duration 9.0±8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN).


RESULTS
176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p=0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p=0.023) were strong and statistically significant predictors of infection.


CONCLUSIONS
Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent.
Rheumatology Unit, L. Sacco University Hospital, Milan, Italy. atzenifabiola@hotmail.com
Fabiola
F
Atzeni
Piercarlo
P
Sarzi-Puttini
Costantino
C
Botsios
Antonio
A
Carletto
Paola
P
Cipriani
Ennio Giulio
EG
Favalli
Elena
E
Frati
Valentina
V
Foschi
Stefania
S
Gasparini
AnnaRita
A
Giardina
Elisa
E
Gremese
Florenzo
F
Iannone
Marco
M
Sebastiani
Tamara
T
Ziglioli
Domenico
D
Biasi
Clodoveo
C
Ferri
Mauro
M
Galeazzi
Roberto
R
Gerli
Roberto
R
Giacomelli
Roberto
R
Gorla
Marcello
M
Govoni
Giovanni
G
Lapadula
Antonio
A
Marchesoni
Fausto
F
Salaffi
Leonardo
L
Punzi
Giovanni
G
Triolo
Gianfranco
G
Ferraccioli
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007239:Infections / Q000139:chemically induced / Q000150:complications* / Q000453:epidemiology; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012042:Registries; D000079424:Tumor Necrosis Factor Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000079424:Tumor Necrosis Factor Inhibitors; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept