Supplementary Material for: Time to Loss of Disease Control Following Guselkumab Withdrawal in Relation to Initial Speed of Response: A Post-Hoc Analysis of the VOYAGE 2 Trial

Background:
Psoriasis is a chronic inflammatory skin disorder typically requiring lifelong treatment. As such, patients may occasionally need treatment breaks. Understanding factors predicting maintenance of disease control during treatment breaks could improve long-term disease management. This post-hoc analysis of data from the Phase 3 VOYAGE 2 clinical trial evaluates how initial speed of response to guselkumab treatment affects time to loss of disease control following treatment withdrawal and identifies baseline characteristics corresponding with maintenance of disease control.

Methods:
Patients with moderate-to-severe plaque psoriasis assigned to treatment withdrawal following achievement of a Psoriasis Area and Severity Index (PASI)90 response after two or four guselkumab doses. Loss of disease control was defined as time to PASI ≥3 and was assessed using Kaplan–Meier analysis. The relationship between baseline characteristics and maintenance of response was evaluated using a Cox proportional hazards model.

Results:
Of patients who were randomized to placebo and switched to guselkumab at Week 16, 149/248 (60%) achieved PASI90 after two guselkumab doses (Week 28). Of patients who were randomized to guselkumab, 377/496 (76%) achieved PASI90 after four guselkumab doses (Week 28), of whom 182 were then re-randomized to withdrawal. Of these, 131 had achieved PASI90 after two guselkumab doses (Week 12) and 51 had achieved PASI90 after four guselkumab doses (Week 28). Maintenance of disease control following guselkumab withdrawal was longer in patients who achieved PASI90 after two versus four guselkumab doses. Lower body mass index, biologic naïve status, and shorter disease duration at baseline corresponded with a longer time to PASI ≥3 following withdrawal.

Conclusion:
Faster initial response to guselkumab resulted in longer maintenance of disease control after treatment withdrawal. These findings may be used to inform personalized dosing strategies with guselkumab, which may increase patient compliance to treatment and improve long-term treatment outcomes.

背景：
银屑病是一种慢性炎症性皮肤病，通常需终身治疗。因此，患者偶尔可能需要暂停治疗。明确治疗中断期间疾病控制维持的预测因素，有助于优化长期疾病管理。本研究对三期VOYAGE 2临床试验数据进行事后分析，旨在评估患者对古塞库单抗治疗的初始应答速度如何影响停药后疾病控制丧失的时间，并确定与疾病控制维持相关的基线特征。

方法：
纳入接受2或4剂古塞库单抗治疗后达到银屑病面积和严重程度指数（PASI）90应答的中重度斑块状银屑病患者，随后暂停治疗。疾病控制丧失定义为PASI≥3的时间点，采用Kaplan-Meier分析评估；基线特征与应答维持的相关性采用Cox比例风险模型分析。

结果：
在随机分配至安慰剂组并于第16周转为古塞库单抗治疗的患者中，248例中有149例（60%）在接受2剂古塞库单抗后（第28周）达到PASI90应答。在随机分配至古塞库单抗组的患者中，496例中有377例（76%）在接受4剂后（第28周）达到PASI90应答，其中182例被重新随机分配至停药组。在这182例中，131例在2剂后（第12周）达到PASI90，51例在4剂后（第28周）达到PASI90。停药后，2剂后达到PASI90的患者其疾病控制维持时间显著长于4剂后达到者。基线时较低的体重指数、生物制剂初治状态及较短的病程，与停药后PASI≥3的出现时间延长相关。

结论：
对古塞库单抗的初始应答越快，停药后疾病控制维持时间越长。这些发现可为古塞库单抗的个性化给药策略提供依据，进而提高患者治疗依从性并改善长期治疗结局。