Cortell-Fuster Clara, Martínez-Gómez María Amparo, Cercós-Lleti Ana Cristina, Climente-Martí Mónica, Díaz-Corpas Tania, Mateu-Puchades Almudena, Revert-Fernández Ángeles
Servicio de Farmacia, Hospital Universitario Doctor Peset, Valencia, Spain.
Servicio de Farmacia, Hospital Universitario Doctor Peset, Valencia, Spain.
Farm Hosp. 2025 Mar-Apr;49(2):79-85. doi: 10.1016/j.farma.2024.04.023. Epub 2024 Jun 8.
Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease.
This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibroma severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment.
Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable.
After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.
外用雷帕霉素是治疗罕见的结节性硬化症面部血管纤维瘤的首选药物治疗方法。我们的药学服务部门研发了一种新的、更先进且更复杂的配方：0.4%雷帕霉素脂质体制剂，其感官特性更佳，活性成分释放曲线更优。本研究的目的是评估脂质体外用雷帕霉素治疗这种罕见疾病面部损伤的有效性和安全性。
这是一项观察性、前瞻性多中心研究。主要通过面部血管纤维瘤严重程度指数（FASI）、研究者整体评估（IGA）评分和皮肤病生活质量指数（DLQI）问卷来评估有效性。为评估雷帕霉素的安全性，报告不良反应，并在治疗期间进行血液检查和血液雷帕霉素水平检测。
纳入11例患者，其中8/11（73%）的患者在治疗24周后根据FASI和IGA评分获得成功治疗。统计分析表明，使用雷帕霉素脂质体制剂治疗后，FASI和IGA评分、红斑及面部血管纤维瘤大小有显著改善（p<0.05）（治疗前FASI，中位数（四分位间距）：6.0（2.0），治疗后FASI：3.5（2.0），p = 0.0063）。5例患者治疗后生活质量也有所改善。关于雷帕霉素的安全性，最常见的不良反应是轻度瘙痒，2例患者报告有红斑，提前终止了治疗。所有血液学检查均正常，血液雷帕霉素水平检测不到。
经过药剂学改进和临床评估，雷帕霉素脂质体制剂在该治疗适应证上被证明是有效且安全的。这种新制剂已作为医院药学服务部门的自配制剂，现在皮肤科医生可开处方使用。当治疗选择有限或不足时，医院药学部门的药物研发往往是治疗罕见病症状的唯一可用药物替代方法。
