Department of Rheumatology, Purpan Teaching Hospital, Toulouse, UMR U1027 INSERM, UMR 1027, Université Paul Sabatier, Toulouse III, France.
Ann Rheum Dis. 2012 Jun;71(6):875-7. doi: 10.1136/annrheumdis-2011-200337. Epub 2012 Feb 25.
To assess the association between a single nucleotide polymorphism in the gene of FCGR3A and the response to treatment with rituximab (RTX) in rheumatoid arthritis (RA).
SMART is a randomised open trial assessing two strategies of re-treatment in patients responding to 1 g infusion of RTX with methotrexate on days 1 and 15 after failure, intolerance or contraindication to tumour necrosis factor (TNF) blockers. Among the 224 patients included, 111 could be genotyped and were included in an ancillary study of SMART. Univariate and multivariate analyses adjusted on disease activity score on 28 joints were performed to assess whether FCGR3A-158V/F polymorphism was associated with European League Against Rheumatism response at week 24.
Among the 111 patients, 90 (81%) were responders of whom 30 (27%) were good responders. V allele carriage was significantly associated with a higher response rate (91% of responders vs 70%, OR 4.6 (95% CI 1.5 to 13.6), p=0.006). These results were also confirmed in rheumatoid factor-positive patients (93% vs 74%, p=0.025). In multivariate analysis, V allele carriage was independently associated with response to RTX (OR 3.8 (95% CI 1.2 to 11.7), p=0.023).
The 158V/F polymorphism of FCGR3A seems to influence the response to RTX in patients with RA after failure, intolerance or contraindication to TNF blockers.
评估 FCGR3A 基因单核苷酸多态性与类风湿关节炎（RA）患者对利妥昔单抗（RTX）治疗反应之间的关联。
SMART 是一项随机开放试验，评估了在对 TNF 阻滞剂出现失败、不耐受或禁忌的情况下，对接受第 1 天和第 15 天 1 g 输注 RTX 联合甲氨蝶呤治疗有反应的患者进行两种再治疗策略。在纳入的 224 例患者中，有 111 例可以进行基因分型，并纳入 SMART 的辅助研究。进行单变量和多变量分析，调整 28 个关节疾病活动评分，以评估 FCGR3A-158V/F 多态性是否与欧洲抗风湿病联盟在第 24 周的反应相关。
在 111 例患者中，90 例（81%）为应答者，其中 30 例（27%）为良好应答者。V 等位基因携带与更高的应答率显著相关（91%的应答者 vs 70%，OR 4.6（95%CI 1.5 至 13.6），p=0.006）。这些结果在类风湿因子阳性患者中也得到了证实（93% vs 74%，p=0.025）。在多变量分析中，V 等位基因携带与 RTX 的应答独立相关（OR 3.8（95%CI 1.2 至 11.7），p=0.023）。
FCGR3A 的 158V/F 多态性似乎影响了对 TNF 阻滞剂出现失败、不耐受或禁忌的 RA 患者对 RTX 的反应。
