Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria.
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.
Rheumatology (Oxford). 2024 Nov 1;63(11):3015-3024. doi: 10.1093/rheumatology/keae435.
To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA.
The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3).
Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients.
CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.
Clinicaltrials.gov, http://clinicaltrials.gov, NCT01500278.
评估基线 RF 水平对培塞丽珠[CZP；不含可结晶片段（Fc）的 TNF 抑制剂（TNFi）]和阿达木单抗（ADA；含 Fc 的 TNFi）在 RA 患者中的药物浓度和疗效的影响。
这项 4 期 EXXELERATE 研究（NCT01500278）是一项为期 104 周、随机、单盲（双盲至第 12 周；此后为研究者盲法）、CZP 与 ADA 头对头比较的 RA 患者研究。在这项事后分析中，我们根据基线 RF 四分位数（≤Q3 或＞Q3）报告药物浓度和疗效结果。
453 例 CZP 随机分组和 454 例 ADA 随机分组患者有基线 RF 四分位数数据（≤Q3：≤204IU/ml；＞Q3：＞204IU/ml）。从第 12 周开始，RF＞204IU/ml 患者的 ADA 浓度曲线下面积（AUC）低于 RF≤204IU/ml 患者；RF≤204IU/ml 和＞204IU/ml 患者的 CZP 浓度 AUC 相似。对于 RF≤204IU/ml 的患者，在第 104 周时，接受 CZP 和 ADA 治疗的患者的疾病活动评分（DAS28）-CRP 相似。对于 RF＞204IU/ml 的患者，在第 104 周时，接受 CZP 治疗的患者的平均 DAS28-CRP 低于接受 ADA 治疗的患者。在第 104 周时，RF＞204IU/ml 的患者中，达到 DAS28-CRP 低疾病活动的患者比例在接受 CZP 治疗的患者中高于接受 ADA 治疗的患者。
在 RF 较高的 RA 患者中，CZP 与维持药物浓度和疗效相关，因此与含 Fc 片段的 TNFi 相比，在这些患者中可能是一种更合适的治疗选择。
Clinicaltrials.gov，http://clinicaltrials.gov，NCT01500278。
