EpiDermE, Université Paris Est Créteil, Créteil, France.
Service de Rhumatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Créteil, France.
JAMA Dermatol. 2022 May 1;158(5):513-522. doi: 10.1001/jamadermatol.2022.0364.
Treatment options for psoriasis (PsO) and psoriatic arthritis (PsA) have evolved significantly throughout the era of biologics. Clinical trials are inadequate to assess the relative long-term efficacy of biologics and are often insufficient regarding safety.
To assess the long-term persistence of different biologic classes to treat PsO and PsA.
DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study involved the administrative health care database of the French health insurance scheme linked to the hospital discharge database. All adults with PsO and PsA who were new users of biologics (not in the year before the index date) from January 1, 2015, to May 31, 2019, were included and followed up through December 31, 2019. Patients hospitalized for PsA in the PsO cohort and for PsO in the PsA cohort in the year before the index date were excluded. Data were analyzed from June 1 to October 31, 2021.
Persistence was defined as the time from biologic therapy initiation to discontinuation and was estimated using the Kaplan-Meier method. Comparison of persistence by biologic class involved using propensity score-weighted Cox proportional hazards regression models and adjustment on specific systemic nonbiologics (time-dependent variables).
A total of 16 892 patients with PsO were included in the analysis (mean [SD] age, 48.5 [13.8] years; 9152 men [54.2%] men). Of these, 10 199 patients (60.4%) started therapy with a tumor necrosis factor (TNF) inhibitor; 3982 (23.6%), with an interleukin 12 and interleukin 23 (IL-12/23) inhibitor; and 2711 (16.0%), with an interleukin 17 (IL-17) inhibitor. An additional 6531 patients with PsA (mean [SD] age, 49.1 [12.8] years; 3565 [54.6%] women) were included; of these, 4974 (76.2%) started therapy with a TNF inhibitor; 803 (12.3%), with an IL-12/23 inhibitor; and 754 (11.5%), with an IL-17 inhibitor. Overall 3-year persistence rates were 40.9% and 36.2% for PsO and PsA, respectively. After inverse probability of treatment weighting and adjustment, the IL-17 inhibitor was associated with higher persistence compared with the TNF inhibitor for PsO (weighted hazard ratio [HR], 0.78 [95% CI, 0.73-0.83]) and PsA (weighted HR, 0.70 [95% CI, 0.58-0.85]) and compared with the IL-12/23 inhibitor for PsA (weighted HR, 0.69 [95% CI, 0.55-0.87]). No difference between the IL-17 inhibitor and IL-12/23 inhibitor for PsO was noted. The IL-12/23 inhibitor was associated with higher persistence than the TNF inhibitor for PsO (weighted HR, 0.76 [95% CI, 0.72-0.80]), with no difference observed for PsA.
The findings of this cohort study suggest that IL-17 inhibitors are associated with higher treatment persistence than the TNF inhibitor for PsO and PsA. Interleukin 17 inhibitors were also associated with higher persistence than the IL-12/23 inhibitor for PsA, with no difference for PsO. However, the persistence rates of all biologics remained globally low at 3 years.
重要性：生物制剂时代，银屑病（PsO）和银屑病关节炎（PsA）的治疗选择已有显著发展。临床试验不足以评估生物制剂的相对长期疗效，且在安全性方面往往不够充分。
目的：评估不同生物制剂类别治疗 PsO 和 PsA 的长期持续情况。
设计、设置和参与者：本全国性队列研究纳入了法国医疗保险计划的医疗保健管理数据库，与医院出院数据库相链接。纳入所有于 2015 年 1 月 1 日至 2019 年 5 月 31 日首次使用生物制剂（索引日期前 1 年无）的新发 PsO 和 PsA 成人患者，并随访至 2019 年 12 月 31 日。索引日期前一年在 PsO 队列中因 PsA 住院和在 PsA 队列中因 PsO 住院的患者被排除在外。数据分析于 2021 年 6 月 1 日至 10 月 31 日进行。
主要结局和测量：持续性定义为从生物治疗开始到停药的时间，使用 Kaplan-Meier 法进行估计。通过倾向评分加权 Cox 比例风险回归模型和对特定的系统非生物制剂（时间依赖性变量）的调整，比较生物制剂类别的持续性。
结果：纳入了 16892 例 PsO 患者进行分析（平均[标准差]年龄，48.5[13.8]岁；9152 例男性[54.2%]男性）。其中，10199 例（60.4%）患者开始接受肿瘤坏死因子（TNF）抑制剂治疗；3982 例（23.6%）患者接受白细胞介素 12 和白细胞介素 23（IL-12/23）抑制剂治疗；2711 例（16.0%）患者接受白细胞介素 17（IL-17）抑制剂治疗。还纳入了 6531 例 PsA 患者（平均[标准差]年龄，49.1[12.8]岁；3565 例[54.6%]女性）。其中，4974 例（76.2%）患者开始接受 TNF 抑制剂治疗；803 例（12.3%）患者接受 IL-12/23 抑制剂治疗；754 例（11.5%）患者接受 IL-17 抑制剂治疗。总体而言，PsO 和 PsA 的 3 年持续性率分别为 40.9%和 36.2%。经过逆概率治疗加权和调整后，与 TNF 抑制剂相比，IL-17 抑制剂与 PsO（加权危险比[HR]，0.78[95% CI，0.73-0.83]）和 PsA（加权 HR，0.70[95% CI，0.58-0.85]）的持续性更高，与 IL-12/23 抑制剂相比，IL-17 抑制剂在 PsA 中的持续性更高（加权 HR，0.69[95% CI，0.55-0.87]）。未观察到 IL-17 抑制剂与 IL-12/23 抑制剂在 PsO 中的差异。与 TNF 抑制剂相比，IL-12/23 抑制剂与 PsO 的持续性更高（加权 HR，0.76[95% CI，0.72-0.80]），但在 PsA 中无差异。
结论和相关性：这项队列研究的结果表明，与 TNF 抑制剂相比，IL-17 抑制剂与 PsO 和 PsA 的治疗持续性更高。IL-17 抑制剂也与 IL-12/23 抑制剂相比，在 PsA 中的持续性更高，而在 PsO 中无差异。然而，所有生物制剂的持久性在 3 年内仍普遍较低。
