The Efficacy of Everolimus for Facial Angiofibromas in Tuberous Sclerosis Complex Patients Treated for Renal Angiomyolipoma/Subependymal Giant Cell Astrocytoma

Wei, Chang-Ching; Hsiao, Yu‐Ping; Gau, Shuo‐Yan; Wu, Yueting; Wu, Chi-Tang; Wu, Meng-Hsuan; Tsai, Jeng-Dau

doi:10.1159/000510222

Cited by 4 publications

(4 citation statements)

References 25 publications

(37 reference statements)

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“…Studies with oral mTOR inhibitors showed concurrent improvement in facial angiofibroma and other TSC skin lesions [28][29][30][31]. However, side effects associated with systemic exposure to mTOR inhibitors may not justify its use solely for the treatment of facial angiofibroma in most cases.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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

View full text Add to dashboard Cite

show abstract

“…Studies with oral mTOR inhibitors showed concurrent improvement in facial angio broma and other TSC skin lesions (30)(31)(32)(33). However, side effects associated with systemic exposure to mTOR inhibitors may not justify its use solely for the treatment of facial angio broma in most cases.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Management of Facial Angiofibroma Related to Tuberous Sclerosis Complex in the United States: Retrospective Analysis of the Natural History Database

Boggarapu

Roberds

Nakagawa

et al. 2022

Preprint

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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 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. Patient features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors. Facial angiofibroma was noted in 1329 (64.4%) patients with TSC. Patients with facial angiofibroma were older on average. TSC2 mutation was more common, and the burden of other TSC-related manifestations was significantly higher in patients with facial angiofibroma. The 6–17 and the 18–45 -year-old age groups, TSC2 mutation, angiomyolipoma, and renal cysts were significantly associated with a higher risk of facial angiofibroma. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Being white and presence of angiomyolipoma were significantly associated with higher use of a topical mTOR inhibitor.CONCLUSIONS: Patients with facial angiofibroma were older and more commonly had a TSC2 mutation. The higher burden of TSC-related manifestations in patients with facial angiofibroma illustrates the importance of accurate diagnosis by dermatologists and referral to a comprehensive multi-disciplinary TSC Clinic for surveillance and management of other TSC manifestations. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor.

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“…In the last few decades, TSC diagnostics, treatment, and surveillance have advanced markedly [ 1 , 5 ]. For instance, everolimus, an mTOR-inhibitor (mTORi), has been found particularly efficient for treating subependymal giant cell astrocytomas (SEGA), angiomyolipomas (AML), facial angiofibromas, and epilepsy in TSC patients, if used continuously [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Childhood tuberous sclerosis complex in southern Sweden: a paradigm shift in diagnosis and treatment

et al. 2023

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Aim To investigate the complete clinical spectrum of individuals with paediatric tuberous sclerosis complex in southern Sweden and explore changes over time. Methods In this retrospective observational study, 52 individuals aged up to 18 years at the study start were followed-up at regional hospitals and centres for habilitation from 2000 to 2020. Results Cardiac rhabdomyoma was detected prenatally/neonatally in 69.2% of the subjects born during the latest ten years of the study period. Epilepsy was diagnosed in 82.7% of subjects, and 10 (19%) were treated with everolimus, mainly (80%) for a neurological indication. Renal cysts were detected in 53%, angiomyolipomas in 47%, astrocytic hamartomas in 28% of the individuals. There was a paucity of standardized follow-up of cardiac, renal, and ophthalmological manifestations and no structured transition to adult care. Conclusion Our in-depth analysis shows a clear shift towards an earlier diagnosis of tuberous sclerosis complex in the latter part of the study period, where more than 60% of cases showed evidence of this condition already in utero due to the presence of a cardiac rhabdomyoma. This allows for preventive treatment of epilepsy with vigabatrin and early intervention with everolimus for potential mitigation of other symptoms of tuberous sclerosis complex.

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The Efficacy of Everolimus for Facial Angiofibromas in Tuberous Sclerosis Complex Patients Treated for Renal Angiomyolipoma/Subependymal Giant Cell Astrocytoma

Cited by 4 publications

References 25 publications

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

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

Characterization and Management of Facial Angiofibroma Related to Tuberous Sclerosis Complex in the United States: Retrospective Analysis of the Natural History Database

Childhood tuberous sclerosis complex in southern Sweden: a paradigm shift in diagnosis and treatment

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