PMID- 16396977
OWN - NLM
STAT- MEDLINE
DCOM- 20060816
LR  - 20181113
IS  - 0003-4967 (Print)
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 65
IP  - 8
DP  - 2006 Aug
TI  - Safety of extended treatment with anakinra in patients with rheumatoid arthritis.
PG  - 1006-12
AB  - OBJECTIVE: To determine the safety profile of anakinra after extended exposure in 
      a diverse clinical trial population of patients with rheumatoid arthritis. 
      METHODS: A six month, randomised, double blind phase comparing anakinra (100 
      mg/day) with placebo was followed by open label anakinra treatment for up to 
      three years in patients with rheumatoid arthritis. Concomitant non-steroidal 
      anti-inflammatory drugs, corticosteroids, and other disease modifying 
      antirheumatic drugs were permitted. RESULTS: In all 1346 patients with rheumatoid 
      arthritis received anakinra for up to three years. Patients had varying levels of 
      disease severity, concomitant drug use, and comorbid conditions. Cumulative, 
      exposure adjusted event (EAE) rates for all adverse events (AEs), serious AEs, 
      and deaths were similar during each year of anakinra treatment; the overall rate 
      (0 to 3 years) was similar to that observed for controls during the blinded 
      phase. The most frequent AEs were injection site reactions (122.26 events/100 
      patient-years), rheumatoid arthritis progression (67.80 events/100 
      patient-years), and upper respiratory infections (26.09 events/100 
      patient-years). The EAE rate of serious infections was higher for patients 
      treated with anakinra for 0 to 3 years (5.37 events/100 patient-years) than for 
      controls during the blinded phase (1.65 events/100 patient-years). However, if 
      the patient was not receiving corticosteroid treatment at baseline, the serious 
      infection rate was substantially lower (2.87 event/100 patient-years). The 
      overall incidence of malignancies was consistent with expected rates reported by 
      SEER. Neutralising antibodies developed in 25 patients, but appeared to be 
      transient in 12; neutralising antibody status did not appear related to 
      occurrence of malignancies or serious infections. There were no clinically 
      significant trends in laboratory data related to anakinra. CONCLUSION: Anakinra 
      is safe and well tolerated for up to three years of continuous use in a diverse 
      population of patients with rheumatoid arthritis.
FAU - Fleischmann, R M
AU  - Fleischmann RM
AD  - University of Texas Southwestern Medical Center at Dallas, Radiant Research, 5939 
      Harry Hines Boulevard, Dallas, TX 75235, USA. royfleischmann@radiantresearch.com
FAU - Tesser, J
AU  - Tesser J
FAU - Schiff, M H
AU  - Schiff MH
FAU - Schechtman, J
AU  - Schechtman J
FAU - Burmester, G-R
AU  - Burmester GR
FAU - Bennett, R
AU  - Bennett R
FAU - Modafferi, D
AU  - Modafferi D
FAU - Zhou, L
AU  - Zhou L
FAU - Bell, D
AU  - Bell D
FAU - Appleton, B
AU  - Appleton B
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20060105
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antibodies)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Glucocorticoids)
RN  - 0 (IL1RN protein, human)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Sialoglycoproteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies/blood
MH  - Antirheumatic Agents/*adverse effects/immunology/therapeutic use
MH  - Arthritis, Rheumatoid/complications/*drug therapy/mortality
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Glucocorticoids/therapeutic use
MH  - Humans
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/complications/mortality
MH  - Respiratory Tract Infections/complications/mortality
MH  - Sialoglycoproteins/*adverse effects/immunology/therapeutic use
MH  - Treatment Outcome
PMC - PMC1798263
EDAT- 2006/01/07 09:00
MHDA- 2006/08/17 09:00
PMCR- 2009/08/01
CRDT- 2006/01/07 09:00
PHST- 2006/01/07 09:00 [pubmed]
PHST- 2006/08/17 09:00 [medline]
PHST- 2006/01/07 09:00 [entrez]
PHST- 2009/08/01 00:00 [pmc-release]
AID - ard.2005.048371 [pii]
AID - ar48371 [pii]
AID - 10.1136/ard.2005.048371 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2006 Aug;65(8):1006-12. doi: 10.1136/ard.2005.048371. Epub 2006 
      Jan 5.