Tumour necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis.
OBJECTIVE
To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA).


METHODS
One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14.


RESULTS
Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels (p<0.03).


CONCLUSIONS
A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.
Cuchacovich
M
M
Rheumatology Section, Department of Medicine, Clinical Hospital University of Chile, Chile. mcuchaco@ns.hospital.uchile.cl
Ferreira
L
L
Aliste
M
M
Soto
L
L
Cuenca
J
J
Cruzat
A
A
Gatica
H
H
Schiattino
I
I
Pérez
C
C
Aguirre
A
A
Salazar-Onfray
F
F
Aguillón
J C
JC
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab