Seattle Rheumatology Associates, Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, 601 Broadway, Suite 600, Seattle, WA, 98122, USA.
Cleveland Clinic, Cleveland, OH, USA.
Arthritis Res Ther. 2020 Mar 6;22(1):43. doi: 10.1186/s13075-020-2126-1.
In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment.
In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed.
Across indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were - 0.83 vs. 0.91, respectively, in patients achieving MDA and - 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo→golimumab-treated patients achieving MDA were - 1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints.
The extent of structural damage inhibition afforded by up to 1 year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect.
ClinicalTrials.gov. NCT02181673. Registered 04 July 2014.
在静脉注射戈利木单抗治疗银屑病关节炎（PsA）的 GO-VIBRANT 试验中，戈利木单抗显著抑制了影像学进展。在事后分析中，我们评估了治疗后根据复合指数定义的疾病活动度评估的总 PsA 改良 Sharp/van der Heijde 评分（SHS）在各个水平的变化。
在这项 3 期、双盲、安慰剂对照试验中，480 名初治、活动性 PsA 患者随机接受静脉注射戈利木单抗 2mg/kg（N=241；第 0 周、第 4 周、每 8 周[q8w]）或安慰剂（N=239；第 0 周、第 4 周、第 12 周、第 20 周），随后接受戈利木单抗（第 24 周、第 28 周、q8w）直至第 52 周。在 474 名具有可评估影像学数据的患者中，对具有不同疾病活动度评估的患者亚组（几种复合指标评估的最小疾病活动度[MDA]、极低疾病活动度[VLDA]、银屑病关节炎疾病活动度评分[PASDAS]、关节炎疾病活动度指数[DAPsA]、临床疾病活动指数[CDAI]），评估了第 24 周和第 52 周时的 SHS 变化。部分（末次观察结转方法）和完全（无应答者方法）缺失数据进行了插补。
在所有指数中，与安慰剂相比，戈利木单抗治疗的患者在第 0 至 24 周时表现出较少的影像学进展，无论是否达到戈利木单抗治疗的疾病活动度状态（例如，在达到 MDA 的患者中，戈利木单抗治疗组的 PsA 改良 SHS 平均变化分别为 -0.83 与 0.91，在未达到 MDA 的患者中，分别为-0.05 与 1.49）。在第 24 周观察到的治疗差异在第 52 周仍持续存在，尽管安慰剂随机患者在第 24 周转为戈利木单抗治疗（例如，从第 0 至 52 周，戈利木单抗-与安慰剂→戈利木单抗治疗的患者达到 MDA 的 PsA 改良 SHS 平均变化分别为-1.16 与 1.19），且无论是否达到低疾病活动度（在未达到 MDA 的患者中，分别为 0.03 与 1.50）。在使用 VLDA、PASDAS、DAPsA 和 CDAI 复合终点评估的疾病活动中观察到一致的模式。
在长达 1 年的静脉注射戈利木单抗治疗期间，结构损伤抑制的程度与 PsA 活性水平相匹配，在持续高疾病活动度的患者中观察到结构损伤的进展更大。在未达到几种复合指数低疾病活动度的患者中，与安慰剂随机的 PsA 患者相比，戈利木单抗随机的患者似乎表现出较少的结构损伤进展，表明在反应中存在潜在的脱节，其中戈利木单抗可以独立于临床效果抑制结构损伤。
ClinicalTrials.gov。NCT02181673。于 2014 年 7 月 4 日注册。
