PMID- 30428897
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20190415
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 13
IP  - 1
DP  - 2018 Nov 14
TI  - Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis.
PG  - 204
LID - 10.1186/s13023-018-0946-8 [doi]
LID - 204
AB  - BACKGROUND: Lymphangioleiomyomatosis is a rare disease caused by unregulated 
      activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus 
      showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but 
      the optimal dose remains unclear. METHODS: We investigated the efficacy and 
      safety of low-dose compared with conventional-dose sirolimus. Clinical data of 39 
      patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment 
      period, 29.6 months) who received sirolimus were retrospectively reviewed. 
      Low-dose sirolimus was defined as any dose that maintained mean blood trough 
      levels lower than those maintained with conventional doses (5-15 ng/mL). RESULTS: 
      Fifty-one percent of patients received low-dose therapy. The rate of decline in 
      lung function decreased after treatment in the whole group (forced expiratory 
      volume in 1 s [FEV(1)], - 0.12 +/- 0.47 [before] vs. 0.24 +/- 0.48% predicted/month 
      [after], p = 0.027; diffusing capacity for carbon monoxide [DLco], - 0.33 +/- 0.61 
      vs. 0.03 +/- 0.26% predicted/month, p = 0.006) compared with before treatment. In 
      the low-dose group, the rate of decline in FEV(1) (- 0.08 +/- 0.38 [before] vs. 
      0.19 +/- 0.51% predicted/month [after], p = 0.264) and DLco (-0.13 +/- 0.62 vs. 
      0.02 +/- 0.28% predicted/month, p = 0.679) showed a numeric trend towards 
      improvement after treatment; however, the conventional-dose group showed 
      significant improvement in FEV(1) (- 0.26 +/- 0.54 [before] vs. 0.22 +/- 0.38 [after] 
      % predicted/month, p = 0.024) and DLco (- 0.55 +/- 0.58 vs. 0.04 +/- 0.25% 
      predicted/month, p = 0.002) after treatment. Adverse events (AEs) occurred in 
      89.7% of patients and the most common AEs was hypercholesterolaemia (43.6%), 
      followed by stomatitis (35.9%). The occurrences of AE were similar between the 
      low- and conventional-dose groups (85.0% vs. 94.7%, p = 0.605). CONCLUSIONS: 
      Low-dose sirolimus may stabilise lung function decline in 
      lymphangioleiomyomatosis patients, but its efficacy appears to be inferior to 
      that of conventional-dose sirolimus.
FAU - Yoon, Hee-Young
AU  - Yoon HY
AD  - Departments of Pulmonary and Critical Care Medicine, Asan Medical Center, 
      University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 
      05505, Republic of Korea.
FAU - Hwang, Jung Jin
AU  - Hwang JJ
AD  - Department of Convergence Medicine, Asan Medical Center, University of Ulsan 
      College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of 
      Korea.
FAU - Kim, Dong Soon
AU  - Kim DS
AD  - Departments of Pulmonary and Critical Care Medicine, Asan Medical Center, 
      University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 
      05505, Republic of Korea.
FAU - Song, Jin Woo
AU  - Song JW
AUID- ORCID: 0000-0001-5121-3522
AD  - Departments of Pulmonary and Critical Care Medicine, Asan Medical Center, 
      University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 
      05505, Republic of Korea. jwsong@amc.seoul.kr.
LA  - eng
GR  - 16-495/Asan Institute for Life Sciences, Asan Medical Center/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181114
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Female
MH  - Forced Expiratory Volume/physiology
MH  - Humans
MH  - Lymphangioleiomyomatosis/*drug therapy/physiopathology
MH  - Male
MH  - Retrospective Studies
MH  - Sirolimus/adverse effects/*therapeutic use
MH  - Treatment Outcome
MH  - Vital Capacity/physiology
PMC - PMC6236936
OTO - NOTNLM
OT  - Low dose
OT  - Lymphangioleiomyomatosis
OT  - Respiratory function tests
OT  - Sirolimus
OT  - Treatment outcome
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study was approved by the Asan 
      Medical Center Institutional Review Board (2016-0480). CONSENT FOR PUBLICATION: 
      Not applicable. COMPETING INTERESTS: The authors declare that they have no 
      competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with 
      regard to jurisdictional claims in published maps and institutional affiliations.
EDAT- 2018/11/16 06:00
MHDA- 2019/04/16 06:00
PMCR- 2018/11/14
CRDT- 2018/11/16 06:00
PHST- 2018/08/02 00:00 [received]
PHST- 2018/10/30 00:00 [accepted]
PHST- 2018/11/16 06:00 [entrez]
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/11/14 00:00 [pmc-release]
AID - 10.1186/s13023-018-0946-8 [pii]
AID - 946 [pii]
AID - 10.1186/s13023-018-0946-8 [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2018 Nov 14;13(1):204. doi: 10.1186/s13023-018-0946-8.