Genetic and clinical biomarkers of tocilizumab response in patients with rheumatoid arthritis

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• 作者：Mar Maldonado-Montoro^a ; ^{mariadelmarmaldonadomontoro@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Marisa Cañ ; adas-Garre^a ; ^{marisacgarre@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Alfonso Gonzá ; lez-Utrilla^b ; ^{agutrilla@wanadoo.es" class="auth_mail" title="E-mail the corresponding author} ; José ; Cristian Plaza-Plaza^c ; ^{jplaza@uc.cl" class="auth_mail" title="E-mail the corresponding author} ; Miguel Á ; ngel Calleja-Herná ; ndez^a ; ^{mangel.calleja.sspa@juntadeandalucia.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tocilizumab ; Rheumatoid arthritis ; GALNT18 ; CD69 ; Effectiveness
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：264-271
• 全文大小：658 K

文摘

The aim of this study was to investigate the influence of clinical and genetic factors on response to tocilizumab (TCZ) response, remission, low disease activity (LDA) and DAS28 improvement.

A retrospective cohort study in 79 RA patients treated with TCZ during 6/18 months of therapy was conducted. CD69(rs11052877), GALNT18(rs4910008), CLEC2D(rs1560011), KCNMB1(rs703505), ENOX1(rs9594987), rs10108210, and rs703297 gene polymorphisms, identified in a recent GWAS as putative predictors of TCZ response, were analysed.

Variables independently associated to satisfactory EULAR response at 6 months were GALNT18-CC genotype (OR_CC/T-:12.8; CI_95%:1.5,108.7; p = 0.02), CD69 gene polymorphism (OR_AA/GG:17.2; CI_95%:2.5,119.6; p = 0.004) and lower number of previous biological therapy, BT (OR: 0.45; CI_95%:0.3, 0.7; p = 0.001). The factors independently associated to higher remission were lower number of previous BT (OR:0.56; CI_95%:0.38, 0.82; p = 0.003), and GALNT18 CC genotype (OR_CT/CC:0.09; CI_95%:0.02,0.45;p = 0.004; OR_TT/CC:0.14; CI_95%:0.02,0.79; p = 0.026). The A-allele of CD69 (OR_{A_/GG}:6.68;CI_95%:1.68,26.51;p = 0.007) and lower number of previous BT (OR:0.50; CI_95%:0.32,0.77; p = 0.002) were independent factors capable to predict higher LDA rates at 6 months. Independent factors associated to higher improvement in DAS28 at 6 months were CD69-AA genotype (B = −0.56; CI_95%:-1.09, −0.03; p = 0.039), GALNT18-CC genotype (B = −0.88;CI_95%:-1.49, −0.27; p = 0.005), subcutaneous administration (B = 1.03; CI_95%:0.44,1.62; p = 0.001) and higher baseline DAS28 (B = 0.82; CI_95%:0.59, 1.05; p = 4.9 × 10⁻¹⁰). Lower number of previous BT was the only independent predictor of satisfactory EULAR response (OR:0.60; CI_95%:0.34,0.88; p = 0.010) and higher remission (OR:0.65; CI_95%:0.46,0.93; p = 0.018) at 18 months. The C-allele of GALNT18 (OR_C-/TT:4.60; CI_95%:1.16, 18.27; p = 0.03) and lower number of previous BT (OR:0.47; CI_95%:0.29,0.74; p = 0.001) were independent factors capable to predict higher LDA rates at 18 months.

In conclusion, RA patients treated with TCZ showed better EULAR response, remission, LDA and DAS28 improvement rates in patients carrying the GALNT18 C-allele or the CD69 A-allele, particularly when lower number of BT were previously administered.