PMID- 25676588
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20181202
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 67
IP  - 5
DP  - 2015 May
TI  - Randomized, double-blind, dose-escalation trial of triptorelin for ovary 
      protection in childhood-onset systemic lupus erythematosus.
PG  - 1377-85
LID - 10.1002/art.39024 [doi]
AB  - OBJECTIVE: To determine the dose of triptorelin that is sufficient to maintain 
      complete ovarian suppression in female patients with childhood-onset systemic 
      lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the 
      length of time needed to achieve ovarian suppression after initiation of 
      triptorelin treatment, and to investigate the safety of triptorelin. METHODS: In 
      this randomized, double-blind, placebo-controlled, dose-escalation study, female 
      patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or 
      placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 
      mug/kg, and the dose was escalated until complete ovarian suppression was 
      maintained. The primary outcome was the weight-adjusted dose of triptorelin that 
      provided complete ovarian suppression in at least 90% of the patients, as 
      determined by gonadotropin-releasing hormone agonist stimulation testing. The 
      secondary outcome was the period of time required to achieve ovarian suppression, 
      as measured by unstimulated follicle-stimulating hormone and luteinizing hormone 
      levels after the initiation of triptorelin treatment. RESULTS: Treatment with 
      triptorelin at a weight-adjusted dose of 120 mug/kg body weight provided sustained 
      complete ovarian suppression in 90% of the patients. After administration of the 
      initial dose of triptorelin, 22 days were required to achieve complete ovarian 
      suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) 
      per 100 patient-months of followup were not higher in the triptorelin group 
      compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 
      8.5). CONCLUSION: High doses of triptorelin are needed to achieve and maintain 
      complete ovarian suppression, but such doses appear to be well tolerated in 
      adolescent female patients with childhood-onset SLE. Our data suggest that a lag 
      time of 22 days after initiation of triptorelin treatment is required before 
      cyclophosphamide therapy is started or continued.
CI  - (c) 2015, American College of Rheumatology.
FAU - Brunner, Hermine I
AU  - Brunner HI
AD  - Cincinnati Children's Hospital Medical Center and University of Cincinnati 
      College of Medicine, Cincinnati, Ohio.
FAU - Silva, Clovis A
AU  - Silva CA
FAU - Reiff, Andreas
AU  - Reiff A
FAU - Higgins, Gloria C
AU  - Higgins GC
FAU - Imundo, Lisa
AU  - Imundo L
FAU - Williams, Calvin B
AU  - Williams CB
FAU - Wallace, Carol A
AU  - Wallace CA
FAU - Aikawa, Nadia E
AU  - Aikawa NE
FAU - Nelson, Shannen
AU  - Nelson S
FAU - Klein-Gitelman, Marisa S
AU  - Klein-Gitelman MS
FAU - Rose, Susan R
AU  - Rose SR
LA  - eng
SI  - ClinicalTrials.gov/NCT00124514
GR  - M01 RR008084/RR/NCRR NIH HHS/United States
GR  - UL1 TR000077/TR/NCATS NIH HHS/United States
GR  - FDA-R-00-2369/PHS HHS/United States
GR  - UL-1-TR-00077/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Luteolytic Agents)
RN  - 08AN7WA2G0 (Triptorelin Pamoate)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
SB  - IM
MH  - Adolescent
MH  - Antirheumatic Agents/*adverse effects
MH  - Cyclophosphamide/*adverse effects
MH  - Double-Blind Method
MH  - Female
MH  - Follicle Stimulating Hormone/metabolism
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*drug therapy
MH  - Luteinizing Hormone/metabolism
MH  - Luteolytic Agents/*administration & dosage
MH  - *Ovulation Inhibition
MH  - Primary Ovarian Insufficiency/chemically induced/*prevention & control
MH  - Time Factors
MH  - Triptorelin Pamoate/*administration & dosage
MH  - Young Adult
PMC - PMC4414812
MID - NIHMS668690
COIS- Conflict of Interest: None of the authors perceive to have a conflict of interest 
      relevant to the conduct of this study.
EDAT- 2015/02/14 06:00
MHDA- 2015/06/30 06:00
PMCR- 2016/05/01
CRDT- 2015/02/14 06:00
PHST- 2014/09/02 00:00 [received]
PHST- 2015/01/06 00:00 [accepted]
PHST- 2015/02/14 06:00 [entrez]
PHST- 2015/02/14 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1002/art.39024 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2015 May;67(5):1377-85. doi: 10.1002/art.39024.