A secondary analysis of the MORE trial suggested a reduction in the rate of invasive breast cancer, and the RUTH trial was powered to evaluate the incidence rates of invasive breast cancer and coronary events in users of raloxifene versus placebo. A predefined secondary analysis was the rate of vertebral fractures. The patients in this trial were postmenopausal and had either established coronary artery disease (CHD), or were at high risk for CHD defined as four cardiac risk factors.
While these patients may seem different from the average rheumatologist’s patient population, I suggest that the individuals in the RUTH trial resemble our patient populations more closely than many of us would like to admit—and certainly closer than the MORE patients. As the role of inflammation in the pathogenesis of CHD is elucidated, we are recognizing the increased incidence of CHD in our populations and the high rates of traditional and disease-related CHD risk among patients with autoimmune illnesses.
From an evidence-based medicine perspective, there are few criticisms of the RUTH trial. It was well designed and well executed, with appropriate power to answer the primary clinical questions. A little less clear is its ability to answer the question on the prevention of vertebral fractures, although the greater numbers than the MORE trial suggest it can, plus it follows patients for a median of five years versus three.
There is no difference in coronary events between patients treated with raloxifene versus those taking placebo. However, the real question for the rheumatologist is whether or not the benefits of raloxifene therapy for reduction in vertebral fractures outweigh the risks of the drug in this group of patients.
As the data from the RUTH trial indicate, the numbers needed to treat to prevent one vertebral fracture, or one incident of breast cancer, are essentially the same as the number of individuals treated to produce an adverse event. (See Table 1, below.) When combined with the null cardiovascular benefit, this study clearly highlights the potential risk of this medication for limited benefit in vertebral fracture reduction among patient populations at high risk of cardiovascular events—such as many of our rheumatologic patients. While the overwhelming majority of patients can take this drug safely, we need to take a look at the risk versus benefit ratio in each of our patients.
Reference
PEDIATRICS
Updating Juvenile Dermatomyositis Criteria
By Kathleen A. Haines, MD
