Université Paris-Est Créteil, UPEC, EpiDermE EA 7379, Créteil, F-94010, France.
Université de Paris, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS-UMR1153), Inserm, Inra, Paris, F-75004, France.
Br J Dermatol. 2021 Mar;184(3):415-424. doi: 10.1111/bjd.19244. Epub 2020 Jul 16.
In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference.
This systematic review and meta-analysis aimed to explore this possibility.
Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495).
We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events.
On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.
在评估银屑病治疗的随机对照试验（RCT）的系统评价和荟萃分析中，治疗组与安慰剂组的严重不良事件（SAE）比例没有差异。将银屑病恶化的病例纳入 SAE 可能解释了这种差异。
本系统评价和荟萃分析旨在探讨这种可能性。
在生活网络 Cochrane 综述（最后一次搜索日期为 2019 年 5 月 8 日）中纳入的 140 项 RCT 中，我们选择了比较生物治疗与安慰剂的 RCT。主要结局是治疗组和安慰剂组在排除银屑病恶化病例后的 SAE 数量。次要结局是特殊关注的不良事件（AE）数量。该试验在 PROSPERO（CRD42019124495）上进行了注册。
我们分析了 51 项 RCT。其中，21 项至少包含一项抗肿瘤坏死因子（TNF）-α 治疗组，15 项抗白细胞介素（IL）-17 治疗组，11 项抗白细胞介素（IL）-23 治疗组和 9 项抗白细胞介素（IL）-12/23 治疗组。纳入银屑病恶化病例后，生物治疗组与安慰剂组发生 SAE 的风险无差异：风险比（RR）1.09，95%置信区间（CI）0.88-1.36。排除银屑病恶化病例后，RR 变得显著（RR 1.30，95% CI 1.02-1.65）。按药物类别分析，RR 分别为抗 TNF-α 1.68（95% CI 1.11-2.54；无缺失数据）；抗 IL-17 1.28（95% CI 0.88-1.85；无缺失数据）；抗 IL-23 0.95（95% CI 0.59-1.52；无缺失数据）和抗 IL-12/23 1.18（95% CI 0.72-1.94；无缺失数据）。由于事件数量较少，我们无法检查生物治疗与安慰剂组之间特殊关注的 AE 之间是否存在潜在差异。
排除银屑病恶化病例后，生物治疗组发生 SAE 的风险高于安慰剂组。鉴于罕见事件，我们无法强调这种 SAE 风险的增加是否与特殊关注的 AE 有关。临床试验中 SAE 的报告必须改变，通过单独报告导致住院和其他 SAE 的疾病恶化，提高透明度。
