Monday, August 30, 2004
Sunday, August 29, 2004
Thursday, August 19, 2004
Thursday, August 12, 2004
Professors Ravinder Maini and Marc Feldmann, both of the Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, will receive the Crafoord Prize on 18 September at the Royal Swedish Academy of Sciences."
Wednesday, August 11, 2004
une 21, 2004 — Atorvastatin has a modest but clinically apparent benefit for rheumatoid arthritis (RA), according to the results of a randomized trial published in the June 19 issue of The Lancet. The commentator suggests that these results support its use for this indication.
"HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function," write Iain B. McInnes, MRCP, PhD, and colleagues from the Glasgow Royal Infirmary, University of Glasgow in the U.K. "Statins therefore have a plausible bioactivity profile in vitro and in vivo that makes them possible therapeutic agents in rheumatoid arthritis to target both vascular risk and synovial inflammation."
In this trial, 116 patients with RA were randomized to receive 40 mg daily of either atorvastatin or placebo in addition to disease-modifying antirheumatic drug (DMARD) therapy.
At six months, change in Disease Activity Score (DAS28) improved on atorvastatin (-0.5; 95% confidence interval [CI], -0.75 to -0.25) compared with placebo (0.03; 95% CI, -0.23 to 0.28; difference between groups, -0.52; 95% CI, -0.87 to -0.17; P = .004). In the atorvastatin group, 18 (31%) of 58 patients achieved the coprimary endpoint of DAS28-European League Against Rheumatism (EULAR) response, as did six (10%) of 58 in the placebo group (odds ratio, 3.9; 95% CI, 1.42-10.72; P = .006).
Compared with placebo, C-reactive protein (CRP) decreased by 50% in the atorvastatin group (P < .001), and erythrocyte sedimentation rate (ESR) decreased by 28% (P = .005). Swollen joint count also decreased more in the atorvastatin group (-2.69 vs. -0.53; mean difference, -2.16; 95% CI, -3.67 to -0.64; P = .006). Both groups had similar frequency of adverse events.
Study limitations include the heterogeneous background of DMARD use, which allowed the possibility of statin-DMARD interactions that could confound outcomes, more patients receiving methotrexate in the atorvastatin group, small study group, and direct effects of statins on hepatic CRP synthesis, which could exaggerate the impression of disease modification.
"Although not indicative for first line use, this effect of atorvastatin could prove beneficial in the context of DMARD combination design, in which a statin offers both vascular protective and adjunctive immune modulatory potential," the authors write. "Whereas existing DMARD therapy might partly reverse vascular risk, our findings suggest that statins can work to reduce traditional and novel vascular risk factors."
Some of the authors report various financial arrangements with Pfizer.
In an accompanying commentary, Lars Klareskog, MD, PhD, and Anders Hamsten, MD, PhD, FRCP, from the Karolinska Institute in Sweden note caveats that should be considered before statins can be recommended for RA in clinical practice. The observed efficacy in this study was marginal compared with both conventional DMARDs and novel biological compounds. The effects of statins on the immune and inflammatory systems are still unknown, and there are no long-term safety data on patients with inflammatory diseases.
"Although of limited size and short-term, their findings support the use of atorvastatin, and presumably of other statins, to prevent cardiovascular disease in patients with rheumatoid arthritis," the editorialists write. "Needless to say, more work is needed to define the long-term effects on inflammatory diseases and cardiovascular comorbidities, and to expand the basic understanding of how various statins affect the immune system."
Lancet. 2004;363:2011-2012, 2015-2021