Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex

Lee, Young In; Kim, Doyoung; Chung, Kee Yang; Shin, Jung U

doi:10.1159/000489089

Cited by 17 publications

(26 citation statements)

References 25 publications

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“…Lee et al investigated the efficacy of sirolimus ointment in 36 patients with AF, including three patients treated for over 1 year. The authors observed no further dramatic improvement after 20 weeks of treatment (14). Although the efficacy of sirolimus gel for AF is greater than that for topical sirolimus using other vehicles (8,11), sirolimus gel may exhibit limited efficacy for enlarged AF, similar to everolimus, which cannot diminish SEGA completely.…”

Section: Discussionmentioning

confidence: 92%

“…Although some previous studies have investigated the efficacy of topical sirolimus for AF among patients with TSC (7,8,(10)(11)(12)(13)(14)(15)(16), the follow-up period was only 6 months in most of these trials. Thus, the efficacy of long-term sirolimus gel treatment remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy of topical sirolimus is thought to achieve a plateau in patients with relatively advanced AF (14,16). Lee et al investigated the efficacy of sirolimus ointment in 36 patients with AF, including three patients treated for over 1 year.…”

Section: Discussionmentioning

confidence: 99%

“…Hofbauer et al reported the first case of a patient with TSC who received systemic sirolimus as immunosuppressive treatment after kidney transplantation, following which AF improvement was observed (9). Recent studies have indicated that topical sirolimus gel/ointment is effective for the treatment of AF in patients with TSC (7,8,(10)(11)(12)(13)(14)(15)(16). Wataya-Kaneda et al conducted a randomized clinical trial to confirm the efficacy of sirolimus gel for AF in patients with TSC.…”

Section: Introductionmentioning

confidence: 99%

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Early Sirolimus Gel Treatment May Diminish Angiofibromas and Prevent Angiofibroma Recurrence in Children With Tuberous Sclerosis Complex

et al. 2020

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Introduction: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous disorder. Angiofibromas (AF), fibrous plaques, and hypopigmented macules are the major skin findings in TSC. Topical sirolimus reduces the volume and redness of AF and other skin findings. However, the efficacy of early intervention and long-term treatment remains to be clarified. We investigated the efficacy of sirolimus gel for AF in children with TSC. Methods: We recruited nine children (five boys; four girls) with TSC and AF. We used 0.2% sirolimus gel over 6 months. We reviewed each patient's medical records and photographs for clinical information and data related to improvements in skin lesions. We evaluated the size of AF, fibrous plaques, and color changes in AF and hypopigmented macules. Results: Age at the initiation of treatment ranged from 3.5 to 11.0 years. The follow-up period ranged from 6 to 36 months (≥24 months in 3 children). Patients presented with papular AF (9), miliary AF (8), AF redness (9), fibrous plaques (5), and hypopigmented macules (2). After 6 months of treatment, improvement of AF size and redness was seen in all nine patients. Patients treated for ≥24 months showed significant decrease in AF size that persisted until the final follow-up. Gradual improvement in fibrous plaques was observed, and marked reduction in size was achieved by 4-18 months. Conclusion: Early sirolimus gel intervention is effective for the treatment of AF and fibrous plaques in children with TSC. Early intervention with sirolimus gel may maintain the skin at near-normal levels in patients with TSC.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early Sirolimus Gel Treatment May Diminish Angiofibromas and Prevent Angiofibroma Recurrence in Children With Tuberous Sclerosis Complex

et al. 2020

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“…thinner and more permeable. 9 With regard to ointment with tablets crushed in petrolatum, the presence of solid fragments may be responsible for the risk of bleeding and an uncomfortable sensation of oily skin has been observed. Recently, Bouguéon et al proposed a cream with 0.1% rapamycin solubilised with 5% Transcutol to avoid any bleeding problem and this oily sensation, with stability data.…”

Section: Introductionmentioning

confidence: 99%

Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas

et al. 2018

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Objectives In recent years, various formulations containing rapamycin, mainly petrolatum-based, have been tested on facial angiofibromas in tuberous sclerosis. They are often poorly tolerated due to irritation and bleeding. In addition, their effectiveness was insufficient in young adults. The objective of this study was to develop and characterise a hydro-alcoholic gel containing solubilised rapamycin. The stability of the product stored at 4°C was evaluated over 1 year. Methods Two different 0.1% rapamycin gels were formulated with or without α-tocopherol and urea. Different methods were used to characterise the gels: HPLC, gas chromatography, pH, visual observation and optical microscopy. A physico-chemical and microbiological stability study was also conducted for 1 year at 4°C. results Gels were physically and microbiologically stable after 1 year at 4°C: organoleptic characteristics and pH unchanged, no significant decrease in rapamycin was observed, tocopherol droplet size was constant and rheological behaviour was not altered. Conclusions This study describes a new gel formulation to improve skin penetration using various excipients to promote skin tolerance. This study provides, for the first time, detailed stability data for a hydro-alcoholic rapamycin gel.

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Topical Sirolimus 0.2% Gel for the Management of Tuberous Sclerosis Complex-Related Cutaneous Manifestations: An Interim Analysis of Postmarketing Surveillance in Japan

Egami¹,

Takahashi²,

Kokubo³

et al. 2023

Dermatol Ther (Heidelb)

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Introduction Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder affecting several organs, including skin. We sought to assess the real-world effectiveness and safety of a topical sirolimus 0.2% gel treatment for TSC-related cutaneous manifestations. Methods We conducted an interim analysis of postmarketing surveillance conducted in Japan over 52 weeks. A total of 635 and 630 patients were included in the safety and efficacy analysis sets, respectively. Improvement rate of overall cutaneous manifestations, responder rate of improvement in individual lesions, adverse events (AEs), adverse drug reactions (ADRs), and patient satisfaction level of topical sirolimus 0.2% gel treatment were evaluated along with patient characteristics associated with the improvement rate of cutaneous manifestations or safety. Results The mean age of the patients was 22.9 years and 46.1% were men. At week 52 of treatment, the overall improvement rate was 74.8% and the responder rate was the highest for facial angiofibroma (86.2%). Overall, the incidence rates of AEs and ADRs were 24.6% and 18.4%, respectively. Efficacy was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.010), duration of use ( p < 0.001), and total dosage ( p = 0.005). Safety was associated with age (< 15, ≥ 15 to < 65, and ≥ 65 years, p = 0.011) and duration of use ( p < 0.001). However, when the broad age group (≥ 15 to < 65) was subcategorized by 10-year intervals, the incidence of ADRs was similar among the age groups with no significant differences. Hepatic or renal impairment or concomitant use of systemic mTOR inhibitors had no effect on the effectiveness or safety. Overall, 53% of patients were “very satisfied” or “satisfied” with the treatment received. Conclusions Topical sirolimus 0.2% gel is effective in the management of TSC-related cutaneous manifestations and generally well tolerated. Age and duration of usage had a significant association with the effectiveness or safety of topical sirolimus 0.2% gel, whereas total dosage had a significant association with the effectiveness. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-00914-2.

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Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex

Cited by 17 publications

References 25 publications

Early Sirolimus Gel Treatment May Diminish Angiofibromas and Prevent Angiofibroma Recurrence in Children With Tuberous Sclerosis Complex

Early Sirolimus Gel Treatment May Diminish Angiofibromas and Prevent Angiofibroma Recurrence in Children With Tuberous Sclerosis Complex

Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas

Topical Sirolimus 0.2% Gel for the Management of Tuberous Sclerosis Complex-Related Cutaneous Manifestations: An Interim Analysis of Postmarketing Surveillance in Japan

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