Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists.
OBJECTIVE
The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.


METHODS
First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.


RESULTS
Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.


CONCLUSIONS
Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
Askling
Johan
J
Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. johan.askling@ki.se
Fored
C Michael
CM
Brandt
Lena
L
Baecklund
Eva
E
Bertilsson
Lennart
L
Feltelius
Nils
N
Cöster
Lars
L
Geborek
Pierre
P
Jacobsson
Lennart T
LT
Lindblad
Staffan
S
Lysholm
Jörgen
J
Rantapää-Dahlqvist
Solbritt
S
Saxne
Tore
T
van Vollenhoven
Ronald F
RF
Klareskog
Lars
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003141:Communicable Diseases / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D005260:Female; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment / Q000379:methods; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha