Tumour necrosis factor (TNF)alpha -308 G/G promoter polymorphism and TNFalpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis

Scand J Rheumatol. 2006 Nov-Dec;35(6):435-40. doi: 10.1080/03009740600904284.


Objective: To investigate the influence of -308 tumour necrosis factor-alpha (TNFalpha) promoter polymorphism and circulating TNFalpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA).

Methods: Eighty-one patients with active RA were genotyped for the -308 TNFalpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28).

Results: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFalpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFalpha over time (p < 0.000001).

Conclusion: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Chile
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Adalimumab