Improved health-related quality of life in patients treated with topical sirolimus for facial angiofibroma associated with tuberous sclerosis complex

Hatano, Takashi; Ohno, Yuki; Imai, Yu; Moritake, Jun; Endo, Kenji; Tamari, Mayumi; Egawa, Shin

doi:10.21203/rs.3.rs-20090/v1

Cited by 2 publications

(8 citation statements)

References 10 publications

(15 reference statements)

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“…Concerning non‐RCT studies, local adverse side effects (LASE) were reported in 34 patients 5,15,17,20,24,25,27,36,38 …”

Section: Resultsmentioning

confidence: 99%

“…LASE included acne, mild irritant contact dermatitis, tingling, transient stinging, dry skin, increased sebum, skin redness and pruritus. Worsening of acne was reported in 8 patients 27,36,38 …”

Section: Resultsmentioning

confidence: 99%

“…Medicines for the treatment of rare diseases do not attract the interest of the pharmaceutical industry. Although several different formulations of topical rapamycin have been proposed from 2010 with good results in terms of efficacy and safety, 40 commercially available compounds have not yet been developed, with the exception of Japan, where it is available as orphan drug (Rapalimus Ⓡ gel; Nobelpharma, Tokyo, Japan) 38,50 . There is also a U.S. patent for a 0.25% to 2% sirolimus cream, but nothing has so far been marketed 20 …”

Section: Discussionmentioning

confidence: 99%

“…The use of topical mammalian target of rapamycin (mTOR) inhibitors in the treatment of facial angiofibromas (FA) in Tuberous sclerosis complex (TSC) is a topic of growing interest following the first report published in 2011, 1 and numerous articles and studies have since been published 2–39 …”

Section: Introductionmentioning

confidence: 99%

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Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex—An update

Balestri¹,

Rizzoli²,

Pedrolli³

et al. 2022

Acad Dermatol Venereol

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Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed in Europe. We conducted a retrospective review with the aim to update the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the optimal concentration and trying to establish which vehicle should be preferred. Thirty‐nine reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 483 patients. An improvement of the lesions has been shown in over 90% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%–1%) were proposed, of which a pharmacological analysis has also been performed. Topical rapamycin can be considered an effective and safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has yet to be established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. However, according to this study, the 0.1% concentration represents the first choice. Long‐term and comparative studies between topical rapamycin formulations are required in order to establish which treatment has a better outcome and lower recurrence rate.

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“…Concerning non‐RCT studies, local adverse side effects (LASE) were reported in 34 patients 5,15,17,20,24,25,27,36,38 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex—An update

Balestri¹,

Rizzoli²,

Pedrolli³

et al. 2022

Acad Dermatol Venereol

View full text Add to dashboard Cite

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“…Various topical formulations of the mTOR inhibitor sirolimus (rapamycin) are effective and generally well tolerated for the management of facial angiofibroma based on several short-term studies [18,19], which was further established over the long term [20,21]. Hatano et al reported improvements in health-related quality of life (HRQoL) in patients treated with sirolimus gel for the management of facial angiofibroma [22]. While the evidence and consensus recommendations suggest the use of topical mTOR inhibitors for the management of facial angiofibroma [3], lack of FDA-approved topical therapy at the time of this study meant there was no standardized formulation available, and many individuals did not have access to topical mTOR inhibitor therapy in the US.…”

Section: Introductionmentioning

confidence: 99%

Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database

Boggarapu¹,

Roberds

Nakagawa

et al. 2022

Orphanet J Rare Dis

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Background Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the mechanistic target of rapamycin (mTOR). Facial angiofibroma can bleed spontaneously, impair eyesight, and cause aesthetic disfiguration causing psychological and social stress. To date, there is little or no evidence on the demographics, and other TSC features associated with facial angiofibroma or the use of mTOR inhibitor for the management of facial angiofibroma. This is a retrospective study of TSC Alliance’s Natural History Database aimed to characterize facial angiofibroma and to evaluate features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors for the management of facial angiofibroma. Data in the NHD was obtained from 18 clinical sites in the US since 2006. Results Of the 2240 patients, 2088 patients were enrolled in the US and data from 2057 patients were included in this analysis. The mean (median) age of overall TSC patients was 22.4 (19.0) years. A total of 69 patients were ≤ 5 years of age. Facial angiofibroma was noted in 1329 (64.6%) patients with TSC. Patients with facial angiofibroma were older on average (Mean: 25.9 [median, 23.0] vs. 16.0 [12.4 years] years, p < 0.0001). In patients with vs. without facial angiofibroma, TSC2 mutation (38.9% vs. 34.8%) was more common than TSC1 mutation (12.3% vs. 18.1%), and the incidence rate of most of the other TSC-related manifestations was significantly higher in patients with facial angiofibroma. Majority of patients had focal seizures (72.8% vs. 60.7%), followed by angiomyolipoma (63.7% vs. 21.8%) and renal cysts (59.4% vs. 33.5%). The age groups, 11–17 (odds ratio [OR], 2.53) and 18–45 years (5.98), TSC2 mutation (1.31), focal seizures (1.50), ADHD (1.47) angiomyolipoma (2.79), and renal cysts (2.63) were significantly associated with a higher risk of facial angiofibroma based on multivariate logistic regression. Abrasive or laser therapy was used by 17.1% and 2.6% patients, respectively. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Overall systemic mTOR inhibitor use was observed in 399 (30.0%) patients for management of one or more TSC manifestations. Use of systemic mTOR inhibitor for facial angiofibroma was noted for 163 (12.3%) patients, among whom only 9 (0.7%) patients used exclusively for the management of facial angiofibroma. Of the patients with facial angiofibroma, 44.6% did not receive any treatment. Significantly higher use of topical mTOR inhibitor was associated with the 11–17 years age group (OR, 1.67), anxiety (1.57), angiomyolipoma (1.51), and renal cysts (1.33). Conclusions The presence of TSC2 mutations and most other TSC-related manifestations was significantly higher in patients with facial angiofibroma. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor and use of systemic mTOR inhibitor for the management of facial angiofibroma or for the other manifestations was noted for 30.0%. About 44.6% of patients did not receive any treatment for the management of facial angiofibroma.

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Improved health-related quality of life in patients treated with topical sirolimus for facial angiofibroma associated with tuberous sclerosis complex

Cited by 2 publications

References 10 publications

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex—An update

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex—An update

Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database

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