A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F23%3A00078450" target="_blank" >RIV/65269705:_____/23:00078450 - isvavai.cz</a>

Result on the web

<a href="https://academic.oup.com/bjd/article/189/5/520/7226135?login=true" target="_blank" >https://academic.oup.com/bjd/article/189/5/520/7226135?login=true</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/bjd/ljad243" target="_blank" >10.1093/bjd/ljad243</a>

Result language

angličtina

Original language name

A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial

Original language description

We carried out a phase II/III double-blind randomized placebo-controlled efficacy and safety trial of a novel rapamycin cream to treat facial angiofibromas. Topical rapamycin treatment improved the appearance of angiofibromas over a 26-week treatment period and was well tolerated. Background Facial angiofibromas (FAs) are a major feature of tuberous sclerosis complex (TSC). Topical rapamycin can successfully treat FAs. A new stabilized cream formulation that protects rapamycin from oxidation has been developed in 0.5% and 1% concentrations. Objectives To assess the efficacy and safety of a novel, stabilized topical rapamycin cream formulation. Methods This multicentre double-blind randomized placebo-controlled dose-response phase II/III study with a parallel design included participants aged 6-65 years with FAs of mild or moderate severity according to the Investigator&apos;s Global Assessment (IGA) scale. Participants were randomized to one of three treatment arms: topical rapamycin 0.5%, topical rapamycin 1% or placebo. Treatment was applied once daily for 26 weeks. Safety and efficacy measures were assessed at days 14, 56, 98, 140 and 182. The primary endpoint was the percentage of participants achieving IGA scores of &apos;clear&apos; or &apos;almost clear&apos; after 26 weeks of treatment. Secondary measures included Facial Angiofibroma Severity Index (FASI) and participant- and clinician-reported percentage-based improvement. Safety measures included the incidence of treatment-emergent adverse events and blood rapamycin concentration changes over time. Results Participants (n = 107) were randomized to receive either rapamycin 1% (n = 33), rapamycin 0.5% (n = 36) or placebo (n = 38). All treated participants were included in the final analysis. The percentage of participants with a two-grade IGA improvement was greater in the rapamycin 0.5% treatment group (11%) and rapamycin 1% group (9%) than in the placebo group (5%). However, this was not statistically significant [rapamycin 0.5%: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.36-8.18 (P = 0.50); rapamycin 1%: OR 1.68, 95% CI 0.33-8.40 (P = 0.53)]. There was a statistically significant difference in the proportion of participants treated with rapamycin cream that achieved at least a one-grade improvement in IGA [rapamycin 0.5%: 56% (OR 4.73, 95% CI 1.59-14.10; P = 0.005); rapamycin 1%: 61% (OR 5.14, 95% CI 1.70-15.57; P = 0.004); placebo: 24%]. Skin adverse reactions were more common in patients following rapamycin application (64%) vs. placebo (29%). Conclusions Both rapamycin cream formulations (0.5% and 1%) were well tolerated, and either strength could lead to clinical benefit in the treatment of FA.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30216 - Dermatology and venereal diseases

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

British Journal of Dermatology

ISSN

0007-0963

e-ISSN

1365-2133

Volume of the periodical

189

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

520-530

UT code for WoS article

001050914800001

EID of the result in the Scopus database

2-s2.0-85175269940