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Abstract：
OBJECTIVE: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA).
METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data.
RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported.
CONCLUSIONS: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.
METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data.
RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported.
CONCLUSIONS: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.
摘要：
目的：评估银屑病和银屑病关节炎（GRAPPA）认可的领域/银屑病关节炎（PsA）相关状况研究和评估组的长期guselkumab有效性。
方法：事后分析使用了DISCOVER-2（NCT03158285）生物学/Janus激酶抑制剂初治参与者的数据，这些参与者患有活动性PsA（≥5个肿胀/≥5个压痛关节，C反应蛋白≥0.6mg/dL)，随机(1:1:1)接受guselkumab,每4或8周(Q4W/Q8W)或安慰剂,交叉接受guselkumab.结果与GRAPPA认可的整体疾病活动的关键领域一致，外周关节炎,轴向疾病，附着点炎/指炎和皮肤牛皮癣（未评估指甲牛皮癣）。通过W112通过不良事件评估PsA相关状况(炎性肠病(IBD)/葡萄膜炎)。在连续结果中，从基线到W100的最小二乘均值变化采用重复测量混合效应模型，以调整基线得分。二元测量应答率是用缺失数据的无应答者填补来确定的。
结果：442/493（90%）的guselkumab随机患者通过W100完成治疗。在使用guselkumab早期减少疾病活动后，在关键PsA领域观察到持久的改善(肿胀/压痛关节，牛皮癣,脊椎疼痛,附着点炎/指炎）通过W100。guselkumabQ4W/Q8W：PsA低疾病活动（LDA）的疾病活动指数62%/59%，附着点炎分辨率61%/70%，dactyitismresolution72%/83%,银屑病面积和严重程度指数改善100%59%/53%，银屑病关节炎疾病活动度评分LDA51%/49%,轻微疾病活动度38%/40%。通过W112，在guselkumab随机分组的患者中没有发生IBD病例，并且报告了1例葡萄膜炎。
结论：在患有活动性PsA的未接受生物学治疗的患者中，guselkumab通过2年在GRAPPA认可的关键领域提供了早期和持久的改进，以相当大的比例实现重要的治疗目标。
方法：事后分析使用了DISCOVER-2（NCT03158285）生物学/Janus激酶抑制剂初治参与者的数据，这些参与者患有活动性PsA（≥5个肿胀/≥5个压痛关节，C反应蛋白≥0.6mg/dL)，随机(1:1:1)接受guselkumab,每4或8周(Q4W/Q8W)或安慰剂,交叉接受guselkumab.结果与GRAPPA认可的整体疾病活动的关键领域一致，外周关节炎,轴向疾病，附着点炎/指炎和皮肤牛皮癣（未评估指甲牛皮癣）。通过W112通过不良事件评估PsA相关状况(炎性肠病(IBD)/葡萄膜炎)。在连续结果中，从基线到W100的最小二乘均值变化采用重复测量混合效应模型，以调整基线得分。二元测量应答率是用缺失数据的无应答者填补来确定的。
结果：442/493（90%）的guselkumab随机患者通过W100完成治疗。在使用guselkumab早期减少疾病活动后，在关键PsA领域观察到持久的改善(肿胀/压痛关节，牛皮癣,脊椎疼痛,附着点炎/指炎）通过W100。guselkumabQ4W/Q8W：PsA低疾病活动（LDA）的疾病活动指数62%/59%，附着点炎分辨率61%/70%，dactyitismresolution72%/83%,银屑病面积和严重程度指数改善100%59%/53%，银屑病关节炎疾病活动度评分LDA51%/49%,轻微疾病活动度38%/40%。通过W112，在guselkumab随机分组的患者中没有发生IBD病例，并且报告了1例葡萄膜炎。
结论：在患有活动性PsA的未接受生物学治疗的患者中，guselkumab通过2年在GRAPPA认可的关键领域提供了早期和持久的改进，以相当大的比例实现重要的治疗目标。
