Oregon Health & Science University, Portland.
Hospital University Marqués de Valdecilla, IDIVAL, Santander, Spain.
Arthritis Rheumatol. 2021 Jan;73(1):110-120. doi: 10.1002/art.41477. Epub 2020 Nov 24.
To report the primary (1-year) results from PREVENT, the first phase III study evaluating secukinumab in patients with active nonradiographic axial spondyloarthritis (SpA).
A total of 555 patients were randomized (1:1:1) to receive subcutaneous secukinumab 150 mg with a loading dose (loading dose [LD] group), secukinumab 150 mg without a loading dose (non-loading dose [NL] group), or placebo weekly and then every 4 weeks starting at week 4. The NL group received placebo at weeks 1, 2, and 3 to maintain blinding. Switch to open-label secukinumab or standard of care was permitted after week 20. The study had 2 independent analysis plans, per European Union and non-US (plan A; week 16) and US (plan B; week 52) regulatory requirements. The primary end point was 40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society (ASAS40) criteria at week 16 (in the LD group) and at week 52 (in the NL group) in tumor necrosis factor inhibitor (TNFi)-naive patients. Safety analyses included all patients who received ≥1 dose of study treatment.
Overall, 481 patients completed 52 weeks of treatment, including 84.3% (156 of 185) in the LD group, 89.7% (165 of 184) in the NL group, and 86.0% (160 of 186) in the placebo group. The proportion of patients who switched to open-label or standard of care between weeks 20 and 48 was 50.8% in the LD group, 47.3% in the NL group, and 64.0% in the placebo group. Both primary and all secondary end points were met at week 16. The proportion of TNFi-naive patients who met ASAS40 was significantly higher for LD at week 16 (41.5%) and NL at week 52 (39.8%) versus placebo (29.2% at week 16 and 19.9% at week 52; both P < 0.05). No new safety findings were reported.
Our findings indicate that secukinumab 150 mg provides significant and sustained improvement in signs and symptoms of nonradiographic axial SpA through 52 weeks. Safety was consistent with previous reports.
报告评估司库奴单抗治疗活动性非放射学中轴型脊柱关节炎（SpA）的首个 III 期研究 PREVENT 的主要（1 年）结果。
共 555 例患者随机（1:1:1）接受皮下司库奴单抗 150mg 加负荷剂量（负荷剂量[LD]组）、司库奴单抗 150mg 无负荷剂量（非负荷剂量[NL]组）或每周安慰剂，然后从第 4 周开始每 4 周 1 次。NL 组在第 1、2 和 3 周接受安慰剂以保持盲法。第 20 周后允许转换为开放标签司库奴单抗或标准治疗。该研究有 2 个独立的分析计划，符合欧盟和非美国（方案 A；第 16 周）和美国（方案 B；第 52 周）监管要求。主要终点是在 TNF 抑制剂（TNFi）初治患者中，第 16 周（LD 组）和第 52 周（NL 组）时根据评估强直性脊柱炎国际协会（ASAS）标准达到 40%疾病活动改善。安全性分析包括接受至少 1 次研究治疗的所有患者。
总体而言，481 例患者完成了 52 周的治疗，包括 LD 组 84.3%（156/185）、NL 组 89.7%（165/184）和安慰剂组 86.0%（160/186）。在第 20 周至 48 周期间，LD 组、NL 组和安慰剂组分别有 50.8%、47.3%和 64.0%的患者转换为开放标签或标准治疗。第 16 周时主要和所有次要终点均达到，LD 组第 16 周（41.5%）和 NL 组第 52 周（39.8%）TNFi 初治患者达到 ASAS40 的比例显著高于安慰剂组（第 16 周 29.2%和第 52 周 19.9%；均 P＜0.05）。未报告新的安全性发现。
我们的研究结果表明，司库奴单抗 150mg 可显著和持续改善非放射学中轴型 SpA 的体征和症状，持续 52 周。安全性与之前的报告一致。
