Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via del Pozzo, 41125, Modena, Italy.
Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy.
Clin Rheumatol. 2021 Oct;40(10):4039-4047. doi: 10.1007/s10067-021-05734-3. Epub 2021 Apr 21.
EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.
Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.
During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.
According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.
欧洲抗风湿病联盟(EULAR)的建议并未针对类风湿关节炎(RA)患者在使用首种生物改善病情抗风湿药(bDMARD)治疗失败后应首选哪种生物 DMARD 做出推荐。特别是，关于在使用阿巴西普(ABA)、托珠单抗(TCZ)和利妥昔单抗(RTX)治疗失败后使用二线 bDMARD 的疗效，数据很少。本研究旨在分析在 RTX、TCZ 或 ABA 治疗失败后，使用肿瘤坏死因子抑制剂(TNFi)或其他作用机制(MOA)的二线药物的保留率。
意大利 GISEA 登记处的 278 例 RA 患者纳入本研究。18%的患者首次使用 RTX，45.7%的患者首次使用 ABA，36.3%的患者首次使用 TCZ，而 129 例患者的二线药物为 TNFi(第 1 组)，149 例患者的二线药物为不同 MOA 的药物(第 2 组)。
中位随访 22 个月(IQR 68)时，129 例患者停止治疗；第 1 组患者较第 2 组患者更频繁地停止治疗( p<0.001)，第 1 组和第 2 组在 104 周时的保留率分别为 33.6±5.7%和 63.6±4.6%( p<0.001)。多变量分析显示，作用机制是维持治疗的唯一预测因素。
根据我们的数据，ABA、RTX 和 TCZ 似乎在二线治疗中也能保持良好的保留率，这表明在非 TNFi 作为一线治疗失败后，可以使用它们。然而，需要专门设计研究，根据一线药物，包括新型靶向合成 DMARDs，评估 RA 更合适的治疗策略。关键点 • 相当比例的类风湿关节炎患者在使用首种生物 DMARD 后治疗失败。 • 关于非 TNF 抑制剂治疗失败后生物 DMARD 的疗效数据很少。 • ABA、RTX 或 TCZ 在首程非 TNF 抑制剂治疗失败后似乎能保持较好的保留率。
