Pharmacy Service, UGC Provincial de Farmacia de Granada, University Hospital Virgen de las Nieves, Granada, Spain.
Pharmacy Service, Hospital de Poniente-El Ejido, El Ejido (Almería), Spain.
J Clin Pharmacol. 2019 Apr;59(4):517-531. doi: 10.1002/jcph.1341. Epub 2018 Nov 20.
We evaluated the influence of clinical, biochemical, and genetic factors on response in 142 patients diagnosed with rheumatoid arthritis, of whom 87 patients were treated with tocilizumab (61.26%) and 55 patients were treated with rituximab (38.7%;) according to the variables European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score, 28 joints (DAS28) at 6, 12, and 18 months. A retrospective prospective cohort study was conducted. Patients carrying the FCGR3A rs396991-TT genotype treated with tocilizumab showed higher EULAR response (OR, 5.075; 95%CI, 1.20-21.33; P = .027) at 12 months, those who were naive for biological disease-modifying antirheumatic drugs (bDMARDs) at the beginning of treatment showed satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6 months. Younger age at start of tocilizumab treatment was associated with satisfactory EULAR response at 18 months and greater remission at 6 and 18 months. Subcutaneous tocilizumab administration was associated with higher remission at 6 months and improved low disease activity rate at 12 months. In patients treated with rituximab, carriers of the FCGR2A rs1801274-TT genotype had higher EULAR response at 6 months (OR, 4.861; 95%CI, 1.11-21.12; P = .035), 12 months (OR, 4.667; p = 0.066, 95%CI, 0.90-24.12; P = .066), and 18 months (OR, 2.487; 95%CI, 0.35-17.31; P = .357), higher remission (OR: 10.625; p = 0.044, CI : 1.07, 105.47) at 6 months, and greater improvement in DAS28 at 12 months (B = 0.782; 95%CI, -0.15 to 1.71; P = .098) and 18 months (B = 1.414; 95%CI, 0.19-2.63; P = .025). The FCGR3A rs396991-G allele was associated with improved low disease activity rate (OR, 4.904; 95%CI, 0.84-28.48; P = .077) and greater improvement in DAS28 (B = -1.083; 95%CI, -1.98 to -0.18; P = .021) at 18 months. Patients with a lower number of previous biological therapies had higher remission at 12 months. We suggest that the FCGR3A rs396991-TT genotype, higher baseline value of DAS28, subcutaneous tocilizumab administration, younger age at the beginning of treatment, and being bDMARD naive are associated with better response to tocilizumab. In patients treated with rituximab, we found better response in those patients with the FCGR2A rs1801274-TT genotype, the FCGR3A rs396991-G allele, and lower number of previous biological therapies.
我们评估了临床、生化和遗传因素对 142 例类风湿关节炎患者应答的影响，其中 87 例接受托珠单抗（61.26%）治疗，55 例接受利妥昔单抗（38.7%）治疗；根据欧洲抗风湿病联盟（EULAR）应答、缓解、低疾病活动度和疾病活动评分 28 关节（DAS28）改善的变量，6、12 和 18 个月时。这是一项回顾性前瞻性队列研究。接受托珠单抗治疗且携带 FCGR3A rs396991-TT 基因型的患者在 12 个月时具有更高的 EULAR 应答（OR，5.075；95%CI，1.20-21.33；P =.027），在开始治疗时对生物 DMARD 药物（bDMARDs）无经验的患者在 6 个月时具有令人满意的 EULAR 应答、更高的缓解率和 DAS28 的更大改善。托珠单抗治疗开始时年龄较小与 18 个月时令人满意的 EULAR 应答和 6 和 18 个月时更高的缓解率相关。皮下托珠单抗给药与 6 个月时更高的缓解率和 12 个月时改善的低疾病活动率相关。在接受利妥昔单抗治疗的患者中，携带 FCGR2A rs1801274-TT 基因型的患者在 6 个月（OR，4.861；95%CI，1.11-21.12；P =.035）、12 个月（OR，4.667；P =.066，95%CI，0.90-24.12；P =.066）和 18 个月（OR，2.487；95%CI，0.35-17.31；P =.357）时具有更高的 EULAR 应答，6 个月时具有更高的缓解率（OR：10.625；P =.044，CI：1.07，105.47），12 个月时 DAS28 改善更大（B = 0.782；95%CI，-0.15-1.71；P =.098）和 18 个月（B = 1.414；95%CI，0.19-2.63；P =.025）。FCGR3A rs396991-G 等位基因与改善的低疾病活动率（OR，4.904；95%CI，0.84-28.48；P =.077）和 DAS28 的更大改善（B =-1.083；95%CI，-1.98-0.18；P =.021）相关，在 18 个月时。先前接受生物治疗次数较少的患者在 12 个月时缓解率更高。我们建议，FCGR3A rs396991-TT 基因型、较高的 DAS28 基线值、皮下托珠单抗给药、治疗开始时的年龄较小和对 bDMARD 无经验与托珠单抗更好的应答相关。在接受利妥昔单抗治疗的患者中，我们发现携带 FCGR2A rs1801274-TT 基因型、FCGR3A rs396991-G 等位基因和先前接受的生物治疗次数较少的患者具有更好的应答。
