Abstract：
OBJECTIVE: 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.
METHODS: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：外用雷帕霉素是治疗罕见结节性硬化症面部血管纤维瘤的首选药物。一个新的,更先进,我们的药房服务开发了复杂的配方：雷帕霉素0.4%脂质体制剂，具有更好的感官特性和更有利的活性成分释放曲线。这项研究的目的是评估脂质体局部雷帕霉素治疗这种罕见疾病中面部损伤的有效性和安全性。
方法：这是一个观察性的，prospective,和多中心研究。主要通过面部血管纤维瘤严重程度指数(FASI)评估疗效,调查员全球评估(IGA)得分，皮肤病学生活质量指数(DLQI)问卷。为了评估雷帕霉素的安全性，报告了不良反应，治疗期间进行血液检查和血液雷帕霉素水平。
结果：包括11例患者，其中8/11（73%）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FASI和IGA评分有显著改善(p<.05)，红斑,用雷帕霉素脂质体制剂治疗后的FA大小(治疗前的FASI，中位数（四分位数间距）：6.0（2.0），治疗后FASI：3.5（2.0），p=.0063）。5名患者在治疗后也提高了生活质量。关于雷帕霉素的安全性，最常见的不良反应是轻度瘙痒，2例患者报告红斑，过早停止治疗。所有血液学检查均正常,血液中的雷帕霉素水平检测不到。
结论：经过盖伦改良和临床评估，雷帕霉素脂质体制剂被证明对这种治疗适应症是有效和安全的。这种新配方作为治安药方列入我院药房,现在可以由皮肤科医生开处方。医院药房的药物开发通常是治疗罕见疾病症状的唯一药物选择，当治疗选择有限或不足时。
方法：这是一个观察性的，prospective,和多中心研究。主要通过面部血管纤维瘤严重程度指数(FASI)评估疗效,调查员全球评估(IGA)得分，皮肤病学生活质量指数(DLQI)问卷。为了评估雷帕霉素的安全性，报告了不良反应，治疗期间进行血液检查和血液雷帕霉素水平。
结果：包括11例患者，其中8/11（73%）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FASI和IGA评分有显著改善(p<.05)，红斑,用雷帕霉素脂质体制剂治疗后的FA大小(治疗前的FASI，中位数（四分位数间距）：6.0（2.0），治疗后FASI：3.5（2.0），p=.0063）。5名患者在治疗后也提高了生活质量。关于雷帕霉素的安全性，最常见的不良反应是轻度瘙痒，2例患者报告红斑，过早停止治疗。所有血液学检查均正常,血液中的雷帕霉素水平检测不到。
结论：经过盖伦改良和临床评估，雷帕霉素脂质体制剂被证明对这种治疗适应症是有效和安全的。这种新配方作为治安药方列入我院药房,现在可以由皮肤科医生开处方。医院药房的药物开发通常是治疗罕见疾病症状的唯一药物选择，当治疗选择有限或不足时。
