Department of Epidemiology, Genentech, San Francisco, CA, USA.
Clin Exp Rheumatol. 2013 Mar-Apr;31(2):189-94. Epub 2012 Dec 13.
There is an association between the FcGRIIIa polymorphism and the development of rheumatoid arthritis (RA). Studies in non-Hodgkin lymphoma demonstrated a relationship between the FcGRIIIa polymorphism and response to anti-CD20 therapies. However, there are currently no published studies evaluating the relationship between this polymorphism and therapeutic response to treatment with anti-CD20 agents such as rituximab in RA. We conducted a study to identify if the FcGRIIIa polymorphism is associated with rituximab efficacy in patients with RA.
Subjects with RA treated with rituximab (cases, n=158) or TNF-α antagonist (controls, n=390) were recruited from the Consortium of Rheumatology Researchers of North America. The FcGRIIIa variant was genotyped for all subjects and longitudinal patient outcomes were assessed using the clinical disease activity index (CDAI). We used a linear regression random effects model to estimate CDAI scores over time with multiple time points nested within patient.
Similar changes in CDAI were observed across the three FcGRIIIa genotypes for the rituximab treated group (VV [4.56, SD 14.5]), VF (7.44, SD 14.9) and FF (4.75, SD 10.8) (p >0.05)] and the TNF-α antagonist therapy treated group [VV (5.12, SD 14.6), VF (6.77, SD 15.9), and FF (4.36, SD 18.2) (p >0.05). Overall, there were similar changes in CDAI at 6 months for rituximab (-5.91, SD 14.1) and anti-TNFs (-5.77, SD 15.5) (p >0.05). The FcGRIIIa genotype was not significantly associated (p=0.86) with treatment response in rituximab treated RA patients compared with TNF-α antagonist therapy treated patients. Baseline CDAI and number of prior biologics were significant predictors of clinical response over time.
Our finding emphasises the idea that determinants of response to treatment are complex and may be dependent upon genetic and phenotypic interactions. Future studies should analyse the interaction between the FcGRIIIa gene, other neighbouring polymorphisms and other phenotypic and environmental factors.
FcGRIIIa 多态性与类风湿关节炎（RA）的发展有关。非霍奇金淋巴瘤的研究表明，FcGRIIIa 多态性与抗 CD20 治疗的反应之间存在关系。然而，目前尚无研究评估该多态性与 RA 患者接受抗 CD20 药物（如利妥昔单抗）治疗的治疗反应之间的关系。我们进行了一项研究，以确定 FcGRIIIa 多态性是否与 RA 患者接受利妥昔单抗治疗的疗效相关。
从北美风湿病研究联合会招募了接受利妥昔单抗（病例，n=158）或 TNF-α 拮抗剂（对照，n=390）治疗的 RA 患者。对所有患者进行 FcGRIIIa 变体基因分型，并使用临床疾病活动指数（CDAI）评估纵向患者结局。我们使用线性回归随机效应模型，通过在患者内嵌套多个时间点来估计随时间变化的 CDAI 评分。
利妥昔单抗治疗组的三种 FcGRIIIa 基因型（VV [4.56，SD 14.5]、VF [7.44，SD 14.9]和 FF [4.75，SD 10.8]）和 TNF-α 拮抗剂治疗组 [VV（5.12，SD 14.6）、VF（6.77，SD 15.9）和 FF（4.36，SD 18.2）] 观察到相似的 CDAI 变化（p>0.05）。总体而言，利妥昔单抗治疗组的 CDAI 在 6 个月时的变化相似（-5.91，SD 14.1），抗 TNF 治疗组的变化相似（-5.77，SD 15.5）（p>0.05）。与 TNF-α 拮抗剂治疗组相比，FcGRIIIa 基因型与利妥昔单抗治疗 RA 患者的治疗反应无显著相关性（p=0.86）。基线 CDAI 和先前生物制剂的数量是随时间推移临床反应的重要预测因素。
我们的发现强调了这样一个观点，即治疗反应的决定因素是复杂的，可能取决于遗传和表型相互作用。未来的研究应分析 FcGRIIIa 基因、其他邻近多态性以及其他表型和环境因素之间的相互作用。
