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Table 1.  
Characteristics of Study Patients
Characteristics of Study Patients
Table 2.  
Response to Etanercept According to Different Genotypesa
Response to Etanercept According to Different Genotypesa
1.
Ryan  C, Kelleher  J, Fagan  MF,  et al.  Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis. Clin Exp Dermatol. 2014;39(4):519-524.
PubMedArticle
2.
Ramírez  J, Fernández-Sueiro  JL, López-Mejías  R,  et al.  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. J Rheumatol. 2012;39(5):1035-1041.
PubMedArticle
3.
Julià  M, Guilabert  A, Lozano  F,  et al.  The role of Fcγ receptor polymorphisms in the response to anti–tumor necrosis factor therapy in psoriasis: a pharmacogenetic study. JAMA Dermatol. 2013;149(9):1033-1039.
PubMedArticle
4.
Cañete  JD, Suárez  B, Hernández  MV,  et al.  Influence of variants of Fcγ receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti–tumour necrosis factor α therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68(10):1547-1552.
PubMedArticle
5.
Morales-Lara  MJ, Conesa-Zamora  P, García-Simón  MS,  et al.  Association between the FCGR3A V158F polymorphism and the clinical response to infliximab in rheumatoid arthritis and spondyloarthritis patients. Scand J Rheumatol. 2010;39(6):518-520.
PubMedArticle
6.
Taylor  W, Gladman  D, Helliwell  P, Marchesoni  A, Mease  P, Mielants  H; CASPAR Study Group.  Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665-2673.
PubMedArticle
7.
Fredriksson  T, Pettersson  U.  Severe psoriasis: oral therapy with a new retinoid. Dermatologica. 1978;157(4):238-244.
PubMedArticle
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Research Letter
December 2015

Influence of Fcγ Receptor Polymorphisms on Response to Anti–Tumor Necrosis Factor Treatment in Psoriasis

Author Affiliations
  • 1Department of Dermatology II, Hospital Universitario Central Asturias, Oviedo, Spain
  • 2Department of Molecular Genetics, Hospital Universitario Central Asturias, Oviedo, Spain
JAMA Dermatol. 2015;151(12):1376-1378. doi:10.1001/jamadermatol.2015.2818

Biological agents have greatly improved the prognosis of psoriasis. However, these treatments are expensive, and 20% to 50% of patients do not achieve an adequate clinical response.1 Therefore, identifying the biomarkers that predict the response could lead to individualized, more effective treatments.1

The anti–tumor necrosis factor (TNF) agents are the group of biological drugs most frequently used to treat psoriasis. Their Fc portion binds specifically to cell-surface Fcγ receptors (FCGR). These receptors may influence the immune response and half-life of the drug.2 Single-nucleotide polymorphisms (SNPs) at genes encoding these receptors are related to differences in their affinity and effector properties.2 The SNP FCGR2A (ENSG00000143226) rs1801274 A/G (amino acid 131 His or Arg) and FCGR3A (ENSG00000203747) rs396991 T/G (Phe or Val at position 158) might confer a higher affinity for IgG binding. The FCGR3A SNP could also affect the expression of cell-surface receptors.3

Previous reports have found an association between these SNPs and different response to biological agents in some tumors and inflammatory or autoimmune diseases.4,5 With respect to psoriasis, few studies have reported this issue.2,3,5 Our objective was to determine whether FCGR2A and FCGR3A SNPs were associated with the response to biological treatment of psoriasis.

Methods

We performed a cross-sectional observation involving 115 Spanish patients with psoriasis recruited from the Department of Dermatology of Hospital Universitario Central Asturias. All participants were older than 18 years and naive to biological treatment. They completed at least 6 months of treatment and provided written informed consent. The ethical committee of the hospital approved this study. Anthropometric and clinical data are shown in Table 1. The disease outcome was measured as the percentage of patients with an improvement of 50% or 75% in their Psoriasis Area and Severity Index7 (PASI 50 or PASI 75) at weeks 12 and 24 after treatment. Improvement by 75% indicated a good response.1

The SNPs rs1801274 and rs396991 were determined through real-time polymerase chain reaction with TaqMan probes (Applied Biosystems). Patients underwent genotyping in duplicate, with a complete concordance between the 2 assays.

Results

Among 115 Spanish patients with psoriasis, the genotype frequencies did not differ from the Hardy-Weinberg equilibrium. Allele and genotype frequencies were close to those reported among white individuals (http://www.ensembl.org/index.html). We found no differences in response by FCGR2A genotype. At a nonsignificant level, patients with the FCGR3A FF (low-affinity) genotype showed better responses than those with a V allele (VF and VV), with the highest difference at week 24 (PASI 50, 39 of 47 patients [83%] vs 46 of 68 patients [68%]). Taking into account the combination of both FCGR SNPs, the presence of the FCGR2A RR (low-affinity) and/or FCGR3A FF genotypes was correlated with better anti-TNF response (PASI 75, week 24: 46 of 61 patients [75%] vs 32 of 54 patients [59%]) but without significant differences. Similar findings were observed for the FCGR2A RR and FCGR3A FF genotypes (18 of 22 patients [82%] vs 60 of 93 patients [65%], respectively). The analysis by biological agent revealed that these results were mainly owing to treatment with etanercept (Table 2).

Discussion

Previous reports have shown controversial results concerning FCGR polymorphisms and treatment response in psoriasis. Morales-Lara et al5 observed better although nonsignificant responses to infliximab in 16 patients with psoriasis and the high-affinity FCGR3A genotype. Ramírez et al2 found better anti-TNF response (at month 6) in 103 patients with psoriasis who had the high-affinity FCGR2A genotype, mainly within the etanercept group. The different structure of etanercept (fusion protein) compared with adalimumab and infliximab (monoclonal antibodies) might favor a major influence in this case. Finally, Julià et al3 found better intermediate responses (at 6-8 weeks) but worse later responses (at 12 weeks) among patients with high-affinity FCGR2A and FCGR3A alleles.

In conclusion, we have identified a possible influence of the FCGR2A and FCGR3A genotypes on anti-TNF response in patients with psoriasis. These results require replication in larger cohorts.

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Article Information

Accepted for Publication: July 6, 2015.

Corresponding Author: Ana Batalla, MD, Department of Dermatology II, Hospital Universitario Central Asturias, 33006 Oviedo, Spain (anacebey@yahoo.es).

Published Online: September 23, 2015. doi:10.1001/jamadermatol.2015.2818.

Author Contributions: Drs Batalla and Coto-Segura had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Coto-Segura.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Batalla, Coto-Segura.

Critical revision of the manuscript for important intellectual content: Coto, Coto-Segura.

Statistical analysis: Batalla, Coto-Segura.

Administrative, technical, or material support: Batalla, Coto.

Study supervision: Coto-Segura.

Conflict of Interest Disclosures: Dr Coto-Segura reports serving as an invited speaker for and receiving grant and research support from AbbVie, Celgene, Janssen-Cilag, Novartis, Pfizer, and Schering-Plough. No other disclosures were reported.

Funding/Support: This study was supported by grant PI 13/00680 from the Spanish Instituto de Salud Carlos III–European Fund for Regional Development.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Ryan  C, Kelleher  J, Fagan  MF,  et al.  Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis. Clin Exp Dermatol. 2014;39(4):519-524.
PubMedArticle
2.
Ramírez  J, Fernández-Sueiro  JL, López-Mejías  R,  et al.  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. J Rheumatol. 2012;39(5):1035-1041.
PubMedArticle
3.
Julià  M, Guilabert  A, Lozano  F,  et al.  The role of Fcγ receptor polymorphisms in the response to anti–tumor necrosis factor therapy in psoriasis: a pharmacogenetic study. JAMA Dermatol. 2013;149(9):1033-1039.
PubMedArticle
4.
Cañete  JD, Suárez  B, Hernández  MV,  et al.  Influence of variants of Fcγ receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti–tumour necrosis factor α therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68(10):1547-1552.
PubMedArticle
5.
Morales-Lara  MJ, Conesa-Zamora  P, García-Simón  MS,  et al.  Association between the FCGR3A V158F polymorphism and the clinical response to infliximab in rheumatoid arthritis and spondyloarthritis patients. Scand J Rheumatol. 2010;39(6):518-520.
PubMedArticle
6.
Taylor  W, Gladman  D, Helliwell  P, Marchesoni  A, Mease  P, Mielants  H; CASPAR Study Group.  Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665-2673.
PubMedArticle
7.
Fredriksson  T, Pettersson  U.  Severe psoriasis: oral therapy with a new retinoid. Dermatologica. 1978;157(4):238-244.
PubMedArticle
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