PMID- 18037627
OWN - NLM
STAT- MEDLINE
DCOM- 20080811
LR  - 20151119
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 67
IP  - 8
DP  - 2008 Aug
TI  - Everolimus in patients with rheumatoid arthritis receiving concomitant 
      methotrexate: a 3-month, double-blind, randomised, placebo-controlled, 
      parallel-group, proof-of-concept study.
PG  - 1090-5
AB  - OBJECTIVES: Everolimus, a proliferation signal inhibitor with disease-modifying 
      properties, may be useful in treating rheumatoid arthritis (RA). This 
      proof-of-concept study assessed efficacy and safety of everolimus in combination 
      with methotrexate (MTX) in patients with refractory RA. METHODS: A multi-centre, 
      randomised, double-blind, placebo-controlled trial was performed in 121 patients 
      with active RA receiving MTX. Patients were randomised to receive everolimus (6 
      mg/day) or placebo. The primary endpoint was the American College of Rheumatology 
      criteria for a 20% improvement in measures of disease activity (ACR20) at 12 
      weeks. RESULTS: There was a rapid onset of action and at 12 weeks the ACR20 
      response rate was significantly higher in the everolimus group (36.1%) than in 
      the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and 
      swollen joint counts, patient's assessment of pain, and patient's and physician's 
      global assessment of disease activity were significantly greater after treatment 
      with everolimus. The most common adverse events (AEs) in the everolimus group 
      were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 
      8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment 
      discontinuation were reported for 16.4% and 10.0% of patients, respectively. 
      Changes in haematological parameters, liver function tests, and lipid levels 
      occurred more frequently with everolimus compared to placebo, but were mild and 
      reversible. CONCLUSIONS: The study indicates that everolimus plus MTX provides 
      clinical benefit with an acceptable safety and tolerability profile. It may offer 
      a new treatment option in RA patients with inadequate response to MTX.
FAU - Bruyn, G A W
AU  - Bruyn GA
AD  - Medisch Centrum Leeuwarden (Zuid), Afd. Reumatologie, Leeuwarden, 8934 AD, The 
      Netherlands. gawbruyn@wxs.nl
FAU - Tate, G
AU  - Tate G
FAU - Caeiro, F
AU  - Caeiro F
FAU - Maldonado-Cocco, J
AU  - Maldonado-Cocco J
FAU - Westhovens, R
AU  - Westhovens R
FAU - Tannenbaum, H
AU  - Tannenbaum H
FAU - Bell, M
AU  - Bell M
FAU - Forre, O
AU  - Forre O
FAU - Bjorneboe, O
AU  - Bjorneboe O
FAU - Tak, P P
AU  - Tak PP
FAU - Abeywickrama, K H
AU  - Abeywickrama KH
FAU - Bernhardt, P
AU  - Bernhardt P
FAU - van Riel, P L C
AU  - van Riel PL
CN  - RADD Study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20071123
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Placebos)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Nat Clin Pract Rheumatol. 2009 Feb;5(2):68-9. PMID: 19092833
MH  - Adult
MH  - Arthritis, Rheumatoid/*drug therapy/pathology
MH  - Chi-Square Distribution
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Male
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - Placebos
MH  - Severity of Illness Index
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - Statistics, Nonparametric
MH  - Treatment Outcome
EDAT- 2007/11/27 09:00
MHDA- 2008/08/12 09:00
CRDT- 2007/11/27 09:00
PHST- 2007/11/27 09:00 [pubmed]
PHST- 2008/08/12 09:00 [medline]
PHST- 2007/11/27 09:00 [entrez]
AID - ard.2007.078808 [pii]
AID - 10.1136/ard.2007.078808 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2008 Aug;67(8):1090-5. doi: 10.1136/ard.2007.078808. Epub 2007 Nov 
      23.