Association of tumour necrosis factor a, b and c microsatellite polymorphisms with clinical disease activity and induction of remission in early rheumatoid arthritis.

Abstract

OBJECTIVE:

To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies.

METHODS:

In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers.

RESULTS:

At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively.

CONCLUSION:

Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.

• Authors: S Laivoranta-Nyman, T Möttönen, P Hannonen, M Korpela, H Kautiainen, M Leirisalo-Repo, H Julkunen, R Luukkainen, M Hakala, K Vuori, A P Laine, A Toivanen, J Ilonen, FIN-RACo Trial Group
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2006 Nov-Dec Vol. 24 Issue 6 Pg. 636-42 ISSN: 0392-856X [Print] Italy
• PMID: 17207378 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• HLA-DR Antigens
• Lymphotoxin-alpha
• Lymphotoxin-beta
• Tumor Necrosis Factor-alpha
• Tumor Necrosis Factors
• Sulfasalazine
• Hydroxychloroquine
• Prednisolone
• Methotrexate

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (drug therapy, genetics, pathology)
• Drug Therapy, Combination
• Female
• HLA-DR Antigens (metabolism)
• Humans
• Hydroxychloroquine (therapeutic use)
• Lymphotoxin-alpha (genetics)
• Lymphotoxin-beta (genetics)
• Male
• Methotrexate (therapeutic use)
• Microsatellite Repeats
• Middle Aged
• Polymorphism, Genetic (genetics)
• Prednisolone (therapeutic use)
• Prognosis
• Remission Induction
• Sulfasalazine (therapeutic use)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (genetics)
• Tumor Necrosis Factors