FCGR2A/CD32AandFCGR3A/CD16AVariants and EULAR Response to Tumor Necrosis Factor-α Blockers in Psoriatic Arthritis: A Longitudinal Study with 6 Months of Followup

Abstract

<jats:sec><jats:title>Objective.</jats:title><jats:p>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<jats:italic>FCGR2A/CD32A</jats:italic>(H131R) and<jats:italic>FCGR3A/CD16A</jats:italic>(V158F) genetic polymorphisms on the EULAR response to tumor necrosis factor-α (TNF-α) blocker therapy in PsA.</jats:p></jats:sec><jats:sec><jats:title>Methods.</jats:title><jats:p>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.<jats:italic>FCGR2A</jats:italic>-R131H and<jats:italic>FCGR3A</jats:italic>-F158V polymorphisms were genotyped. Potential correlations between clinical response and the<jats:italic>FCGR2A</jats:italic>-R131H and<jats:italic>FCGR3A</jats:italic>-F158V polymorphisms were evaluated.</jats:p></jats:sec><jats:sec><jats:title>Results.</jats:title><jats:p>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<jats:italic>FCGR2A</jats:italic>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 &lt; 0.025). This association was due mainly to the group of patients treated with etanercept. No correlation was found for the<jats:italic>FCGR3A</jats:italic>polymorphism. Similarly, no effect of C-reactive protein levels was observed.</jats:p></jats:sec><jats:sec><jats:title>Conclusion.</jats:title><jats:p>Our data indicate that<jats:italic>FCGR2A</jats:italic>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.</jats:p></jats:sec>

Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis

“…30 Furthermore, in some rheumatoid arthritis patients, TNF blocking has shown to induce psoriasis, 31,32 clearly supporting the existence of very different pathogenic mechanisms. Recently, pharmacogenetic studies of FCGR2A and FCGR3A gene variants and anti-TNF therapy response have provided suggestive evidence for opposite genetic effects between rheumatoid arthritis and Crohn's disease, 33 rheumatoid arthritis and psoriatic arthritis 34 and even between rheumatoid arthritis and psoriasis. 20 Taken together, these results support the existence of different TNFrelated pathways and, consequently, different biologic mechanisms by which TNF blocking is an effective treatment.…”

Genetic, Epigenetic and Pharmacogenetic Aspects of Psoriasis and Psoriatic Arthritis

“…146 Furthermore, PsA patients with high-affinity FCGR2A (p.H131R) genotypes (homozygous wild-type or heterozygous combinations) achieved a EULAR response at 6 months compared with patients with the lowaffinity genotype (homozygous mutant). 147 Although these results require confirmation in larger prospective cohorts, they do suggest that variants affecting genes involved in general immunity and the TNF-a signaling pathway might functionally affect the response to TNF-a inhibitors.…”

Pharmacogenomics of Multifactorial Diseases: A Focus on Psoriatic Arthritis

“…However, the introduction of PsAspecific PGBMs is realizable upon the careful design of specific molecular PGx assays, taking into consideration the robustness, sensitiveness, rapidity and manageability requirements for the clinical implementation. To date, very few techniques have been applied for the detection of such PGBMs: sequencing-based typing (SBT), real-time PCR and the MassArray technologies [29,39,41,42]. All of them allow the specific allelic discrimination of the SNPs of interest and therefore can be utilized according to the laboratory equipment and needs.…”

“…The FCGR2A gene (1q23.3) codes for an Fc receptor protein and is localized on the cell surface, where it mediates the phagocytosis mechanisms and the elimination of the immune complexes [24,41].…”