Session Information
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
The rs396991 polymorphism of FCGR3A alters the Fcγ Receptor Type IIIA function by enhancing or diminishing the affinity to the Fc of immunoglobulins (1) by the substitution of a valine (V) for a phenylalanine (F) at amino acid position 158. FCGR3A polymorphism has already been associated with the biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) response in patients with rheumatoid arthritis and Psoriatic Arthritis (1,2). Our study was carried out to evaluate the influence of the FCGR3A – 158 V/Fpolymorphism on the therapeutic response to anti TNFα in the DESIR (Devenir des SpondyloarthrItes (SpA) Récentes) cohort.
Methods:
All patients included in the DESIR cohort fulfilling the Assessment of SpondyloArthritis international Society (ASAS) diagnosis criteria for axial SpA and who received TNFα blockers at least 8 weeks were included in our study. Univariate and multivariate analyses by Chi square test and logistic regression were performed to assess whether FCGR3A-158V/Fpolymorphism was associated with ASAS 40 response after at least 8 weeks of treatment (3).
Results:
Among the 147 patients who received TNF blockers in DESIR cohort, 139 could be genotyped of whom 52 patients (37%) were responders. FCGR3A-158V/V polymorphism was significantly associated with a lower response rate (17% of responders for VV genotype vs 38 % of responders for VF genotype and 47 % of responders for FF genotype, p=0.016). In multivariate analysis (taking into account of the presence of radiographic sacroiliitis, abnormal VS or CRP levels, HLA–B27 positivity, peripheral arthritis, psoriasis, and smoking status at baseline), FCGR3A-158V/Vpolymorphism was independently associated with a lower response rate to TNF-α blockers (risk of response to TNF-blockers in case of V allele carriage: OR (95% CI) = 0.44 (0.20 to 0.96) (p=0.041).
Conclusion:
In the Desir cohort, FCGR3A158 VVgenotype was associated with a lower response rate to TNF-α blockers in SpA. This association has already been described in previous publications in rheumatoid arthritis patients (1). A higher affinity to the Fc region of antiTNFα could influence their clearance from the circulation. Further studies involving more axial SpA patients should be performed to confirm this association.
This work received an institutionnal support by the French society of rheumatology.
REFERENCES
(1) Tutuncu Z., Kavanaugh A., Zvaifler N et al., FcG Receptor Type IIIA Polymorphisms Influence Treatment Outcomes in Patients With Inflammatory Arthritis Treated With Tumor Necrosis Factor G –Blocking Agents, ARTHRITIS & RHEUMATISM Vol. 52, No. 9, September 2005, pp 2693–2696 DOI 10.1002/art.21266
(2) Ruyssen-Witrand A, Rouanet S, Combe B, et al. Fcγ receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012 Jun;71(6):875-7
(3) Moltó A, Paternotte S, Claudepierre P, et al. Effectiveness of tumor necrosis factor α blockers in early axial spondyloarthritis: data from the DESIR cohort. Arthritis Rheumatol. 2014 Jul;66(7):1734-44
To cite this abstract in AMA style:
LUXEMBOURGER C, Molto A, Claudepierre P, Nigon D, Cantagrel AG, Dougados M, CONSTANTIN A, Ruyssen Witrand A. FCGR3A-158V/F Polymorphism Is Associated with a Lower Response Rate to Tumor Necrosis Factor α Blockers in Early Axial Spondyloarthritis: Data from the DESIR Cohort [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/fcgr3a-158vf-polymorphism-is-associated-with-a-lower-response-rate-to-tumor-necrosis-factora-i%c2%b1-blockers-in-early-axial-spondyloarthritis-data-from-the-desir-cohort/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/fcgr3a-158vf-polymorphism-is-associated-with-a-lower-response-rate-to-tumor-necrosis-factora-i%c2%b1-blockers-in-early-axial-spondyloarthritis-data-from-the-desir-cohort/