Steroids for RA: The argument heats up again

A group of researchers from the Mayo Clinic propose in an editorial in the October 2005 issue of the Journal of Rheumatology that, far from harming the cardiovascular (CV) system, glucocorticoids (GCs) “might actually reduce the risk of cardiovascular disease (CVD) in patients with RA” by lowering the background level of inflammation

Although GCs have been implicated in increased CVD risk in several settings, Drs John M Davis III, Hilal Maradit-Kremers, and Sherine E Gabriel think that the situation in RA patients might be different. They suggest that RA patients differ from the general population because of their high level of inflammatory mediators and that “antagonism of such mediators by GCs might lead to reduced risk of CVD.”GCs linked to contradictory CV effectsThis is an interesting proposal, since steroid exposure has been suspected in the twofold increased risk of CVD in patients with RA, and other traditional CV risk factors do not fully explain the high rate of CV problems associated with RA. With the growing recognition of the role of inflammation in CV damage, other effects of steroids are attracting research attention. “Inflammation plays a fundamental role in the pathogenesis of CVD in RA,” Davis writes.Davis notes that 30% to 50% of RA patients in recent therapeutic trials report having taken GCs and that rheumatologists commonly use these drugs as “bridge therapy” while waiting for slow-acting DMARDs (or insurance reimbursement) to kick in and as treatment for RA flares. Despite decades of use, surprisingly little is known about the long-term effects of GCs in RA patients, particularly with regard to the cardiovascular system. For example, GCs might worsen CVD risk by increasing lipid levels, worsening glucose tolerance, increasing hypertension, or increasing obesity. Conversely, GCs might reduce CVD risk by reducing systemic inflammation. The fact that effective treatment of systemic inflammation with DMARDs is associated with reduced CV mortality suggests that the latter effect is important, Davis says. “These associations between episodic fluctuations in level of systemic inflammation and onset of cardiovascular events suggest the possibility that using GCs to control flares of disease activity may actually lower the risk of cardiovascular events.” An intriguing finding from epidemiologic studies is that RA flares might trigger CV events. Davis et al point out that the risk of a CV event is independent of the duration of RA and that the risk of sudden CV death and silent myocardial infarction increases very early in the RA disease process. “These associations between episodic fluctuations in level of systemic inflammation and onset of cardiovascular events suggest the possibility that using GCs to control flares of disease activity may actually lower the risk of cardiovascular events,” the authors write.Obviously, the tangled relationship between GC exposure, RA, cardiovascular risk factors, and CVD requires a lot more research. Meanwhile, Davis et al write, “[E]radication of inflammation in RA appears important, not only for the joints, but also for the longevity of the cardiovascular system. Use of GCs in early RA and targeted use to treat flares continues to be reasonable and possibly beneficial. However, limiting chronic exposure and employing careful measures to prevent osteoporosis, infection, and other steroid-induced sequelae are critical.”In a second editorial in the same issue of the journal, Drs Liron Caplan, Anthony S Russell, and Frederick Wolfe advise a considerably more cautious approach [2]. “Short-term outcomes are clearly improved with glucocorticoids. Studies that employ a brief exposure to steroids and subsequent tapering are similarly encouraging. In the small minority of patients uncontrolled on traditional DMARDS in combination with biologics, a regimen of limited steroid use probably still makes sense,” Caplan (Washington University School of Medicine, St Louis, MO) tells rheumawire. “Limit exposure, use prophylactic calcium and vitamin D, and in patients with lung disease, consider pneumococcal vaccine.” Caplan predicts that as pharmacoepidemiologic techniques become more powerful, evidence of toxicity at progressively lower levels of GC exposure will emerge. He says that physicians should be aware of the adverse effects associated with GCs and take practical steps to prevent them.”For example,” Caplan says, “Limit exposure, use prophylactic calcium and vitamin D, and in patients with lung disease, consider pneumococcal vaccine. It would not be unreasonable to systematically monitor patients on steroids for the broad spectrum of adverse outcomes attributed to their use.”(Source: (1) Davis JM, Maradit-Kremers H, Gabriel SE. Use of low-dose glucocorticoids and the risk of cardiovascular morbidity and mortality in rheumatoid arthritis: What is the true direction of effect? J Rheum 2005; 32:1856-1862. (2) Caplan L, Russell AS, Wolfe F. Steroids for rheumatoid arthritis: The honeymoon revisited (once again). J Rheum 2005; 32:1863-1865: Rheumawire: Joint and Bone: October 2005.)