银屑病疾病活动度及其他风险因素对银屑病和银屑病关节炎患者血清尿酸水平的影响——一项来自三项司库奇尤单抗3期试验汇总数据的分析
Impact of psoriasis disease activity and other risk factors on serum urate levels in patients with psoriasis and psoriatic arthritis-a analysis of pooled data from three phase 3 trials with secukinumab.
作者信息
Dehlin Mats, Fasth Andreas E R, Reinhardt Maximilian, Jacobsson Lennart T H
机构信息
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Medical Affairs, Novartis Sverige AB, Kista, Sweden.
出版信息
Rheumatol Adv Pract. 2021 Feb 18;5(1):rkab009. doi: 10.1093/rap/rkab009. eCollection 2021.
OBJECTIVES
Our aims were to determine if the Psoriasis Area Severity Index (PASI) score and serum urate (SU) levels were associated at baseline and whether the change in PASI score during 12 weeks of treatment resulted in a significant change in SU, adjusted for relevant confounders.
METHODS
Data from patients with psoriasis/PsA ( = 1042/204) in three phase 3 randomized control trials treated with secukinumab (dose 300 mg, = 628) or placebo ( = 414) were pooled. At baseline, values for SU, PASI and the following covariates were assessed: age, sex, BMI, estimated glomerular filtration rate, and medication with diuretics. To assess the changes in PASI (ΔPASI) and SU (Δurate), the differences (week 12 minus baseline) in patients receiving the active drug were used. Multivariable linear regression, adjusting for covariates, was used to assess the association between PASI and SU at baseline with all patients pooled and to assess the association between Δurate and ΔPASI over 12 weeks of treatment with secukinumab.
RESULTS
The degree of skin involvement of psoriasis showed a statistically significant, albeit modest, association with SU ( = 0.014, < 0.0001 univariately), whereas known risk factors for hyperuricaemia had a much larger impact cross-sectionally at baseline ( = 0.33, < 0.0001). Furthermore, a substantial improvement in PASI score resulted in only a modest decrease of SU over 12 weeks of treatment with secukinumab ( = 0.014, < 0.0001 univariately).
CONCLUSIONS
There is a statistically significant, albeit modest, association with both extent and change in PASI score and SU in patients with psoriasis, compatible with a potential pathophysiological relationship between urate and psoriasis.
TRIAL REGISTRATION
ERASURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01365455; FIXTURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01358578; SCULPTURE: clinicaltrials.gov, https://clinicaltrials.gov, NCT01406938.
目的
我们的目标是确定银屑病面积和严重程度指数（PASI）评分与血清尿酸（SU）水平在基线时是否相关，以及在12周治疗期间PASI评分的变化是否会导致SU发生显著变化，并对相关混杂因素进行校正。
方法
汇总三项3期随机对照试验中接受司库奇尤单抗（剂量300mg，n = 628）或安慰剂（n = 414）治疗的银屑病/银屑病关节炎患者（n = 1042/204）的数据。在基线时，评估SU、PASI的值以及以下协变量：年龄、性别、体重指数、估计肾小球滤过率和利尿剂用药情况。为了评估PASI（ΔPASI）和SU（Δ尿酸）的变化，使用接受活性药物治疗患者的差异（第12周减去基线）。采用多变量线性回归，并对协变量进行校正，以评估所有汇总患者基线时PASI与SU之间的关联，以及司库奇尤单抗治疗12周期间Δ尿酸与ΔPASI之间的关联。
结果
银屑病的皮肤受累程度与SU显示出统计学上显著的关联，尽管程度较小（单变量分析p = 0.014，p < 0.0001），而高尿酸血症的已知危险因素在基线时的横断面影响要大得多（p = 0.33，p < 0.0001）。此外，在司库奇尤单抗治疗的12周内，PASI评分的显著改善仅导致SU适度下降（单变量分析p = 0.014，p < 0.0001）。
结论
银屑病患者的PASI评分与SU在程度和变化方面存在统计学上显著的关联，尽管程度较小，这与尿酸和银屑病之间潜在的病理生理关系相符。
试验注册
ERASURE：clinicaltrials.gov，https://clinicaltrials.gov，NCT01365455；FIXTURE：clinicaltrials.gov，https://clinicaltrials.gov，NCT01358578；SCULPTURE：clinicaltrials.gov，https://clinicaltrials.gov，NCT01406938。
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