PMID- 24884602
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20220408
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 13
DP  - 2014 May 17
TI  - Safety and tolerability of canakinumab, an IL-1beta inhibitor, in type 2 diabetes 
      mellitus patients: a pooled analysis of three randomised double-blind studies.
PG  - 94
LID - 10.1186/1475-2840-13-94 [doi]
AB  - BACKGROUND: We aimed to assess the safety and tolerability of different doses of 
      canakinumab versus placebo in patients with type 2 diabetes mellitus (T2DM). 
      METHODS: Data were pooled from three studies in 1026 T2DM patients with different 
      routes of administration, treatment regimens and follow-up duration. Canakinumab 
      groups were categorised as low (0.03 mg/kg i.v. once; N = 20), intermediate (0.1 
      and 0.3 mg/kg i.v. once, 5 and 15 mg s.c. monthly; N = 247), medium (1.5 mg/kg 
      i.v. once, 50 mg s.c. monthly and 150 mg s.c. once; N = 268), and high doses (10 
      mg/kg i.v. once and 150 mg s.c. monthly; N = 137) and compared with placebo (N = 
      354). Incidences of adverse events (AEs), serious AEs (SAEs), discontinuations 
      due to AEs, deaths, AEs of special interest related to interleukin-1beta inhibition 
      and T2DM disease, and laboratory abnormalities related to haematology and 
      biochemistry parameters were reported. Safety was also analysed by age (<65, >/=65) 
      and gender. RESULTS: Average exposure across all groups was  approximately  6 months (maximum 
      ~17 months). No dose response in AEs was observed but a trend towards more 
      patients having at least one AE across canakinumab groups relative to placebo 
      (P = 0.0152) was observed. SAEs were few and the incidence rate for most 
      canakinumab groups was lower than that of placebo group except for the high-dose 
      group (0.94% versus 0.58% per month in placebo). A total of five patients 
      discontinued treatment due to AEs across treatment groups. No death was reported 
      in any of the three studies. A small, non-significant increase in the incidence 
      rate of infection AEs was observed on canakinumab groups relative to placebo. 
      Canakinumab was associated with mostly mild decreases in WBC, neutrophils and 
      platelet counts. Additionally, mild increases in SGPT, SGOT and bilirubin were 
      reported. Overall, despite small differences, no clinically relevant findings 
      were observed with respect to laboratory values and vital signs. CONCLUSIONS: 
      This pooled analysis demonstrated that canakinumab was safe and well tolerated 
      over a treatment period up to 1.4 years at the four pooled doses evaluated, in 
      agreement with safety findings reported in the individual studies.
FAU - Howard, Campbell
AU  - Howard C
AD  - Novartis Pharmaceuticals Corporation, USEH 100-214, One Health Plaza, East 
      Hanover, NJ 07936-1080, USA. campbell.howard@novartis.com.
FAU - Noe, Adele
AU  - Noe A
FAU - Skerjanec, Andrej
AU  - Skerjanec A
FAU - Holzhauer, Bjorn
AU  - Holzhauer B
FAU - Wernsing, Margaret
AU  - Wernsing M
FAU - Ligueros-Saylan, Monica
AU  - Ligueros-Saylan M
FAU - Thuren, Tom
AU  - Thuren T
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140517
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-1beta)
RN  - 37CQ2C7X93 (canakinumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/*administration & dosage/*adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Cardiovascular Diseases/chemically induced/diagnosis
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Gastrointestinal Diseases/chemically induced/diagnosis
MH  - Humans
MH  - Interleukin-1beta/*antagonists & inhibitors/metabolism
MH  - Male
MH  - Middle Aged
PMC - PMC4033489
EDAT- 2014/06/03 06:00
MHDA- 2014/11/02 06:00
PMCR- 2014/05/17
CRDT- 2014/06/03 06:00
PHST- 2014/03/10 00:00 [received]
PHST- 2014/05/10 00:00 [accepted]
PHST- 2014/06/03 06:00 [entrez]
PHST- 2014/06/03 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
PHST- 2014/05/17 00:00 [pmc-release]
AID - 1475-2840-13-94 [pii]
AID - 10.1186/1475-2840-13-94 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2014 May 17;13:94. doi: 10.1186/1475-2840-13-94.