Rheumatology Department, Hôpital Saint-Antoine, Assistance Publique - Hopitaux de Paris (AP-HP), Paris, France.
Biochemistry Department, Hôpital Tenon, AP-HP, Paris, France.
RMD Open. 2019 Jul 21;5(2):e000897. doi: 10.1136/rmdopen-2019-000897. eCollection 2019.
To comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA).
We evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response.
Of the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) -0.12 ng/µg (-0.58 to 0.31) vs 0.04 (-0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (-0.05 g/L (-0.11 to -0.01) vs -0.01 g/L (-0.02 to 0.01), p<0.001). When considering the patients' responses to treatment, improved biomarkers were mainly observed in the EULAR responders in each treatment group.
TNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA.
ClinicalTrials.gov Identifier NCT01000441, registered on 22 October 2009.
为了比较二线肿瘤坏死因子抑制剂（TNFis）与其他生物制剂对类风湿关节炎（RA）患者心血管疾病（CVD）风险相关生物标志物的差异影响。
我们评估了 RA 患者的脂蛋白相关载脂蛋白 ApoA1 和 ApoB100 及脂蛋白（a）（Lp(a)）血清水平，以及作为胰岛素抵抗替代物的瘦素/脂联素比值（LAR），这些生物标志物来自 Rotation Or Change（ROC）试验中的患者，他们在基线和 24 周时接受二线 TNFis 或另一种生物制剂（托珠单抗（TCZ）、利妥昔单抗或阿巴西普）治疗。我们比较了每组和根据 EULAR 反应的生物标志物水平变化。
ROC 试验共纳入 300 例患者，其中 203 例纳入研究，二线 TNFis 组 96 例，其他生物制剂组 107 例。无论组间如何，基线至 24 周期间，生物标志物均未恶化。与 TNFi 相比，其他生物制剂组的 LAR 改善更明显（中位数（IQR）-0.12ng/µg（-0.58 至 0.31）vs 0.04ng/µg（-0.19 至 0.43），p=0.033），而 TCZ 治疗后 Lp(a)水平的改善也比 TNFi 更明显（-0.05g/L（-0.11 至-0.01）vs -0.01g/L（-0.02 至 0.01），p<0.001）。当考虑患者对治疗的反应时，每个治疗组的 EULAR 反应者中主要观察到生物标志物的改善。
TNFis 和非 TNFis 对 TNFis 控制不佳的 RA 患者的 CVD 风险相关生物标志物改善无影响。与 TNFis 相比，TCZ 可能与更好的 Lp(a)和 LAR 改善相关。这种改善可能与良好的治疗反应有关，从而支持 RA 良好控制的必要性。
ClinicalTrials.gov 标识符 NCT01000441，于 2009 年 10 月 22 日注册。
