PMID- 23040887
OWN - NLM
STAT- MEDLINE
DCOM- 20130626
LR  - 20211021
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 131
IP  - 2
DP  - 2013 Feb
TI  - Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes.
PG  - 461-7.e1-5
LID - S0091-6749(12)01309-7 [pii]
LID - 10.1016/j.jaci.2012.07.055 [doi]
AB  - BACKGROUND: Hypereosinophilic syndromes (HESs) are chronic disorders that require 
      long-term therapy to suppress eosinophilia and clinical manifestations. 
      Corticosteroids are usually effective, yet many patients become corticosteroid 
      refractory or develop corticosteroid toxicity. Mepolizumab, a humanized 
      monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a 
      double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, 
      corticosteroid-responsive subjects with HESs. OBJECTIVE: We evaluated long-term 
      safety and efficacy of mepolizumab (750 mg) in HES. METHODS: MHE100901 is an 
      open-label extension study. The primary end point was the frequency of adverse 
      events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of 
      mepolizumab, and development of antimepolizumab antibodies were also explored. 
      RESULTS: Seventy-eight subjects received 1 to 66 mepolizumab infusions each 
      (including mepolizumab infusions received in the placebo-controlled trial). Mean 
      exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 
      9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the 
      first year, declining to 461 events per 100 subject-years after 48 months. 
      Serious AEs, including 1 death, were reported by the investigator as possibly due 
      to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 
      20.0 to 0 mg in the first 24 weeks. The median average daily dose for all 
      subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects 
      were prednisone free without other HES medications for >/= 12 consecutive weeks. No 
      neutralizing antibodies were detected. Twenty-four subjects withdrew before study 
      completion for death (n = 4), lack of efficacy (n = 6), or other reasons. 
      CONCLUSION: Mepolizumab was well tolerated and effective as a long-term 
      corticosteroid-sparing agent in PDGFRA-negative HES.
CI  - Published by Mosby, Inc.
FAU - Roufosse, Florence E
AU  - Roufosse FE
AD  - Department of Internal Medicine, Hopital Erasme, Institute for Medical 
      Immunology, Universite Libre de Bruxelles, Gosselies, Belgium.
FAU - Kahn, Jean-Emmanuel
AU  - Kahn JE
FAU - Gleich, Gerald J
AU  - Gleich GJ
FAU - Schwartz, Lawrence B
AU  - Schwartz LB
FAU - Singh, Anish D
AU  - Singh AD
FAU - Rosenwasser, Lanny J
AU  - Rosenwasser LJ
FAU - Denburg, Judah A
AU  - Denburg JA
FAU - Ring, Johannes
AU  - Ring J
FAU - Rothenberg, Marc E
AU  - Rothenberg ME
FAU - Sheikh, Javed
AU  - Sheikh J
FAU - Haig, Ann E
AU  - Haig AE
FAU - Mallett, Stephen A
AU  - Mallett SA
FAU - Templeton, Deborah N
AU  - Templeton DN
FAU - Ortega, Hector G
AU  - Ortega HG
FAU - Klion, Amy D
AU  - Klion AD
LA  - eng
GR  - ZIA AI001130-03/ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121004
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 90Z2UF0E52 (mepolizumab)
SB  - IM
MH  - Adolescent
MH  - Adrenal Cortex Hormones/adverse effects/therapeutic use
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*adverse effects/immunology/*therapeutic use
MH  - Double-Blind Method
MH  - Eosinophilia/drug therapy/immunology
MH  - Female
MH  - Humans
MH  - Hypereosinophilic Syndrome/*drug therapy/immunology
MH  - Male
MH  - Middle Aged
MH  - Time
MH  - Young Adult
PMC - PMC3558744
MID - NIHMS412741
EDAT- 2012/10/09 06:00
MHDA- 2013/06/28 06:00
PMCR- 2014/02/01
CRDT- 2012/10/09 06:00
PHST- 2012/02/20 00:00 [received]
PHST- 2012/07/08 00:00 [revised]
PHST- 2012/07/19 00:00 [accepted]
PHST- 2012/10/09 06:00 [entrez]
PHST- 2012/10/09 06:00 [pubmed]
PHST- 2013/06/28 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - S0091-6749(12)01309-7 [pii]
AID - 10.1016/j.jaci.2012.07.055 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2013 Feb;131(2):461-7.e1-5. doi: 
      10.1016/j.jaci.2012.07.055. Epub 2012 Oct 4.