FCGR2A/CD32A and FCGR3A/CD16A variants and EULAR response to tumor necrosis factor-α blockers in psoriatic arthritis: a longitudinal study with 6 months of followup.

Abstract

OBJECTIVE:

The efficacy of antibody-based biological therapies currently used in psoriatic arthritis (PsA) depends not only on their blocking effect on the targeted molecule but also on their binding affinity to genetically defined variants of cell-surface Fc-γ receptors. Our objective was to assess the potential influence of functionally relevant FCGR2A/CD32A (H131R) and FCGR3A/CD16A (V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA.

METHODS:

In total 103 patients with PsA starting anti-TNF-α therapy were included. The efficacy of therapy was evaluated according to EULAR response criteria at 3 and 6 months. FCGR2A-R131H and FCGR3A-F158V polymorphisms were genotyped. Potential correlations between clinical response and the FCGR2A-R131H and FCGR3A-F158V polymorphisms were evaluated.

RESULTS:

EULAR response (moderate plus good) was 85.4% at 3 months and 87.4% at 6 months, while good EULAR response was 61.2% and 62.1%, respectively. More patients with high-affinity FCGR2A genotypes (homozygous or heterozygous combinations) achieved a EULAR response at 6 months compared to patients with the low-affinity genotype (RR; p = 0.034, adjusted comparison error rate < 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for the FCGR3A polymorphism. Similarly, no effect of C-reactive protein levels was observed.

CONCLUSION:

Our data indicate that FCGR2A polymorphism may influence the response to TNF-α blockers (namely etanercept) in PsA in a direction opposite to that previously found in patients with rheumatoid arthritis.

• Authors: Julio Ramírez, José Luis Fernández-Sueiro, Raquel López-Mejías, Carlos Montilla, Maite Arias, Concepción Moll, Mercé Alsina, Raimon Sanmarti, Francisco Lozano, Juan D Cañete
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 39 Issue 5 Pg. 1035-41 (May 2012) ISSN: 0315-162X [Print] Canada
• PMID: 22467926 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• FCGR2A protein, human
• FCGR3A protein, human
• Immunoglobulin G
• Receptors, IgG
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Etanercept
• Methotrexate

Topics

• Adult
• Antirheumatic Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy, genetics)
• Etanercept
• Female
• Follow-Up Studies
• Genetic Variation
• Humans
• Immunoglobulin G (therapeutic use)
• Longitudinal Studies
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Receptors, IgG (genetics)
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)