PMID- 23400715
OWN - NLM
STAT- MEDLINE
DCOM- 20130522
LR  - 20220317
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 65
IP  - 4
DP  - 2013 Apr
TI  - Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus 
      erythematosus: a phase I randomized, controlled, dose-escalation study.
PG  - 1011-21
LID - 10.1002/art.37824 [doi]
AB  - OBJECTIVE: To evaluate the safety and tolerability of multiple intravenous (IV) 
      doses of sifalimumab in adults with moderate-to-severe systemic lupus 
      erythematosus (SLE). METHODS: In this multicenter, double-blind, 
      placebo-controlled, sequential dose-escalation study, patients were randomized 
      3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 
      weeks to week 26, then followed up for 24 weeks. Safety assessment included 
      recording of treatment-emergent adverse events (AEs) and serious AEs. 
      Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and 
      disease activity was assessed. RESULTS: Of 161 patients, 121 received sifalimumab 
      (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 
      received placebo. Patients were predominantly female (95.7%). At baseline, 
      patients had moderate-to-severe disease activity (mean SLE Disease Activity Index 
      score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. 
      In the sifalimumab group versus the placebo group, the incidence of >/=1 
      treatment-emergent AE was 92.6% versus 95.0%, >/=1 serious AE was 22.3% versus 
      27.5%, and >/=1 infection was 67.8% versus 62.5%; discontinuations due to AEs 
      occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n=4) versus 2.5% (n=1). 
      Serum sifalimumab concentrations increased in a linear and dose-proportional 
      manner. Inhibition of the type I IFN gene signature was sustained during 
      treatment in patients with a high baseline signature. No statistically 
      significant differences in clinical activity (SLEDAI and British Isles Lupus 
      Assessment Group score) between sifalimumab and placebo were observed. However, 
      when adjusted for excess burst steroids, SLEDAI change from baseline showed a 
      positive trend over time. A trend toward normal complement C3 or C4 level at week 
      26 was seen in the sifalimumab groups compared with baseline. CONCLUSION: The 
      observed safety/tolerability and clinical activity profile of sifalimumab support 
      its continued clinical development for SLE.
CI  - Copyright (c) 2013 by the American College of Rheumatology.
FAU - Petri, Michelle
AU  - Petri M
AD  - Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. 
      mpetri@jhmi.edu
FAU - Wallace, Daniel J
AU  - Wallace DJ
FAU - Spindler, Alberto
AU  - Spindler A
FAU - Chindalore, Vishala
AU  - Chindalore V
FAU - Kalunian, Kenneth
AU  - Kalunian K
FAU - Mysler, Eduardo
AU  - Mysler E
FAU - Neuwelt, C Michael
AU  - Neuwelt CM
FAU - Robbie, Gabriel
AU  - Robbie G
FAU - White, Wendy I
AU  - White WI
FAU - Higgs, Brandon W
AU  - Higgs BW
FAU - Yao, Yihong
AU  - Yao Y
FAU - Wang, Liangwei
AU  - Wang L
FAU - Ethgen, Dominique
AU  - Ethgen D
FAU - Greth, Warren
AU  - Greth W
LA  - eng
SI  - ClinicalTrials.gov/NCT00482989
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interferon-alpha)
RN  - XOY1YA7RMC (sifalimumab)
SB  - IM
CIN - Z Rheumatol. 2013 Oct;72(8):827-9. PMID: 24043298
MH  - Adult
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects/pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunologic Factors/*administration & dosage/adverse effects/pharmacokinetics
MH  - Interferon-alpha/antagonists & inhibitors
MH  - Lupus Erythematosus, Systemic/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Severity of Illness Index
MH  - Treatment Outcome
PMC - PMC3654174
EDAT- 2013/02/13 06:00
MHDA- 2013/05/23 06:00
CRDT- 2013/02/13 06:00
PHST- 2012/03/09 00:00 [received]
PHST- 2012/12/04 00:00 [accepted]
PHST- 2013/02/13 06:00 [entrez]
PHST- 2013/02/13 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - 10.1002/art.37824 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2013 Apr;65(4):1011-21. doi: 10.1002/art.37824.