PMID- 36905480
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230503
IS  - 2193-8210 (Print)
IS  - 2190-9172 (Electronic)
VI  - 13
IP  - 5
DP  - 2023 May
TI  - Topical Sirolimus 0.2% Gel for the Management of Tuberous Sclerosis 
      Complex-Related Cutaneous Manifestations: An Interim Analysis of Postmarketing 
      Surveillance in Japan.
PG  - 1113-1126
LID - 10.1007/s13555-023-00914-2 [doi]
AB  - 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.
CI  - (c) 2023. The Author(s).
FAU - Egami, Akemi
AU  - Egami A
AD  - Nobelpharma Co., Ltd., Tokyo, Japan.
FAU - Takahashi, Shinji
AU  - Takahashi S
AD  - Nobelpharma Co., Ltd., Tokyo, Japan.
FAU - Kokubo, Takeshi
AU  - Kokubo T
AD  - Nobelpharma Co., Ltd., Tokyo, Japan.
FAU - Boggarapu, Sreedevi
AU  - Boggarapu S
AD  - Nobelpharma America LLC., Bethesda, MD, 20814, USA.
FAU - Beresford, Eric
AU  - Beresford E
AD  - Nobelpharma America LLC., Bethesda, MD, 20814, USA. 
      eric.beresford@nobelpharma-us.com.
LA  - eng
PT  - Journal Article
DEP - 20230311
PL  - Switzerland
TA  - Dermatol Ther (Heidelb)
JT  - Dermatology and therapy
JID - 101590450
PMC - PMC10149422
OTO - NOTNLM
OT  - Adverse drug reactions
OT  - Adverse events
OT  - Angiofibroma
OT  - Effectiveness
OT  - Mechanistic target of rapamycin inhibitors
OT  - Patient satisfaction
OT  - Postmarketing surveillance
OT  - Sirolimus topical
OT  - Tuberous sclerosis complex
COIS- All authors are employees of Nobelpharma.
EDAT- 2023/03/12 06:00
MHDA- 2023/03/12 06:01
PMCR- 2023/03/11
CRDT- 2023/03/11 11:16
PHST- 2022/10/28 00:00 [received]
PHST- 2023/02/23 00:00 [accepted]
PHST- 2023/03/12 06:01 [medline]
PHST- 2023/03/12 06:00 [pubmed]
PHST- 2023/03/11 11:16 [entrez]
PHST- 2023/03/11 00:00 [pmc-release]
AID - 10.1007/s13555-023-00914-2 [pii]
AID - 914 [pii]
AID - 10.1007/s13555-023-00914-2 [doi]
PST - ppublish
SO  - Dermatol Ther (Heidelb). 2023 May;13(5):1113-1126. doi: 
      10.1007/s13555-023-00914-2. Epub 2023 Mar 11.