BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. TRIAL REGISTRATION ClinicalTrials.gov. NCT02181673. Registered 04 July 2014.

中文翻译：

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在静脉注射戈利木单抗治疗的活动性银屑病关节炎患者中，影像学进展在复合指标定义的疾病活动水平上的抑制作用：一项三期，双盲，安慰剂对照试验的结果。

背景技术在银屑病关节炎（PsA）中静脉注射golimumab的GO-VIBRANT试验中，golimumab显着抑制了放射学进展。在事后分析中，我们评估了治疗后整个PsA修改的Sharp / van der Heijde评分（SHS）在复合指数定义的疾病活动水平上的变化。方法在这项三阶段，双盲，安慰剂对照试验中，480名无生物学活性的PsA初次接受治疗的患者随机接受静脉注射戈利木单抗2 mg / 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），然后是golimumab（第24周，第28周，第8周）至第52周。患者亚组中的SHS变化由24周和52周定义通过几种综合措施评估的疾病活动（最低疾病活动[MDA]，极低疾病活动[VLDA]，在474名具有可评估的影像学数据的患者中，对事后评估了银屑病关节炎疾病活动评分[PASDAS]，银屑病关节炎中的疾病活动[DAPsA]，临床疾病活动指数[CDAI]。推算部分（最后观察携带的方法）和完全（无响应方法）缺失的数据。结果在各个指标上，无论通过golimumab实现的疾病活动状态如何，从0周到24周，经golimumab治疗的患者的影像学进展均低于安慰剂治疗的患者（例如，经PsA修饰的SHS的平均变化分别为-0.83和0.91。 ，达到MDA的患者分别为-0.05和1.49（未达到MDA的患者）。在第24周观察到的治疗差异一直持续到52周，尽管安慰剂随机分组的患者在第24周过渡到golimumab（例如，达到MDA的golimumab与安慰剂→golimumab治疗的患者相比，从0周到52周PsA修饰的SHS的平均变化分别为-1.16对1.19）。不管是否达到较低的疾病活性（未达到MDA的患者分别为0.03对1.50）。使用VLDA，PASDAS，DAPsA和CDAI复合终点评估的疾病活动观察到一致的模式。结论长达一年的静脉注射戈利木单抗治疗提供的结构性损伤抑制程度与PsA活性水平相当，在持续较高疾病活动性的患者中观察到结构性损伤的进展更大。在多个综合指标中未达到较低疾病活动水平的患者中，与安慰剂随机分组的PsA患者相比，golimumab随机分组的患者表现出的结构性损害进展要少得多，这说明反应之间存在潜在的脱节，其中golimumab可以独立于临床效果而抑制结构性损害。试验注册ClinicalTrials.gov。NCT02181673。2014年7月4日注册。