Biologic Drug Survival in Pediatric Psoriasis: A Retro-Prospective Observational Study

N. Murashkin, R. A. Ivanov
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Abstract

Background. Irrational selection of biological therapy leads to its inefficiency and early cancellation, aggravating the course of psoriasis and worsening the quality of life, which has negative socio-economic consequences associated with the cost of initiating and providing the patient with a new biological agent. Currently there are no clearly defined strategies and unified protocols for therapeutic tactics regarding the choice and switching of biological drugs in children with psoriasis, which requires research aimed at studying the survival of biological therapy in order to draw up evidence-based recommendations with a high evidence base. Aims — study aims to determine survival rate and significant predictors of biological therapy discontinuation. Methods. A retro-prospective observational study was conducted, which included patients with psoriasis vulgaris, aged 4 to 18 years, who had previously received or needed biological therapy. The data of patients over an 8-year period (from 2015 to 2023) were analyzed. Follow-up was performed from initiation to discontinuation of biological therapy, in cases where outcomes were unknown data was censored. Analysis of therapy survival was carried out using the Kaplan–Meier method with curve construction, the assessment of intergroup differences was carried out using a log rank test. Identification of significant predictors of biological therapy discontinuation was carried out using the Cox multivariate regression method. Results. 430 cases of biological therapy were selected from patients with psoriasis vulgaris aged 5 to 18 years. The highest survival rate of biological therapy was obtained for ustekinumab — 54.9 months, the lowest values — for etanercept (26.7 months). The survival values of adalimumab — 33.9 months and secukinumab — 34.5 months did not statistically significantly differ from each other (p = 0.387). Predictors of early discontinuation of biological therapy were established: presence of a burdened family history (HR = 3.861, p = 0.006); delayed prescription of biological therapy — 2 years from the date of diagnosis (HR = 1.447, p = 0.045); long-term ( 6 months) use of methotrexate (HR = 3.085, p 0.001) or cyclosporine (HR = 4.538, p 0.001) previous to the biological treatment; the presence of comorbidity (inflammatory bowel diseases (HR = 4.938, p = 0.001), metabolic syndrome (HR = 3.947, p 0.001) or psoriatic arthritis (HR = 2.337, p 0.001). Conclusions. Proved the inexpediency of long-term immunosuppressive treatment with non-biological drugs and the need for early prescription of biological therapy. In the presence of a burdened family history and disease duration 2 years since the diagnosis of psoriasis, ustekinumab or secukinumab are recommended as first-line biological therapy in children, the use of which is also associated with a longer duration of treatment and a lower risk of developing adverse events in patient with metabolic syndrome. In active Crohn’s disease, adalimumab is most recommended, followed by a possible switch to ustekinumab. Secukinumab is the drug of choice for patients diagnosed with psoriatic arthritis.
小儿银屑病的生物制剂存活率:一项回顾性观察研究
背景。不合理地选择生物疗法会导致治疗效率低下和提前取消治疗,加重银屑病的病程,恶化患者的生活质量,并因开始治疗和为患者提供新的生物制剂所需的费用而产生负面的社会经济后果。目前,在儿童银屑病患者选择和更换生物制剂方面,还没有明确的策略和统一的治疗方案,这就需要对生物制剂治疗的存活率进行研究,以便制定出具有高度证据基础的循证建议。目的--研究旨在确定生物疗法的存活率和终止治疗的重要预测因素。研究方法进行了一项回顾性观察研究,研究对象包括曾接受或需要生物疗法的 4 至 18 岁寻常型银屑病患者。研究分析了患者在8年期间(2015年至2023年)的数据。随访时间从开始使用生物疗法到停止使用,如果结果未知,则对数据进行删减。治疗存活率分析采用卡普兰-梅耶法(Kaplan-Meier)构建曲线,组间差异评估采用对数秩检验。采用 Cox 多元回归法确定终止生物疗法的重要预测因素。结果从 5 至 18 岁的寻常型银屑病患者中选取了 430 例进行生物治疗。乌斯特库单抗的生物治疗存活率最高,为54.9个月,依那西普(etanercept)的存活率最低,为26.7个月。阿达木单抗的存活期为33.9个月,secukinumab的存活期为34.5个月,两者之间没有显著的统计学差异(p = 0.387)。生物疗法早期停药的预测因素已经确定:存在家族病史负担(HR = 3.861,p = 0.006);生物疗法处方延迟--自诊断之日起 2 年(HR = 1.447,p = 0.045);长期(6 个月)使用甲氨蝶呤(HR = 3.085,P 0.001)或环孢素(HR = 4.538,P 0.001);合并症(炎症性肠病(HR = 4.938,P = 0.001)、代谢综合征(HR = 3.947,P 0.001)或银屑病关节炎(HR = 2.337,P 0.001)。结论证明长期使用非生物制剂药物进行免疫抑制治疗是不合理的,需要尽早使用生物制剂治疗。如果存在家族病史,且银屑病确诊后病程已满两年,建议将乌斯特库单抗或塞库库单抗作为儿童的一线生物疗法,使用这两种药物还能延长治疗时间,降低代谢综合征患者出现不良反应的风险。对于活动性克罗恩病,最推荐使用阿达木单抗,然后可能改用乌斯特库单抗。塞库单抗是银屑病关节炎患者的首选药物。
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