Dr. Keystone also discussed other composite indices for assessing RA, including the RAPID3 (routine assessment of patient index data), which he believes is a predictor of radiologic progression.3 “TSS [Total Sharp Score] means less than the probability of radiologic progression and may lead you astray,” he said, because a substantial change in TSS is needed to register any noticeable change in physical functioning.
He reviewed several landmark studies showing benefits of combined therapies, infliximab, adalimumab, or etanercept with methotrexate, for patients at various stages of disease progression. He pointed out that RA patients today tend to be seen earlier in their disease progression, with more moderate symptoms, and receive higher doses of methotrexate than in the past.
Hot Topics in Osteoporosis Treatment Reviewed
Paul Miller, MD, CCD, medical director of the Colorado Center for Bone Research, reviewed a number of current topics in osteoporosis treatment, including the issue of drug “holidays” from bisphosphonate treatments. He outlined these drugs’ unusual properties; for example, that they are not metabolized by the body. Half of the treatment binds to the bone while half is secreted by the kidney. Uptake, retention, and detachment of the drug from bone surfaces continue during treatment and beyond, at different rates of detachment for different bisphosphonates, and when recycled into the bloodstream, the drugs are still biologically active. These properties “allow us to consider a break from treatment,” he said.
Drug holidays from bisphosphonates are not the current standard of care in the United States, despite concerns about potential long-term side effects, Dr. Miller said. On September 11, 2011, the Food and Drug Administration (FDA) convened an advisory panel to consider whether it should change its prescribing label for bisphosphonates. The committee opted not to make a change at this time, acknowledging that there is no consensus to support regulatory restriction on duration of drug use, although it recommended that the labeling be updated. The FDA continues to express concerns about long-term safety and efficacy, with limited data to demonstrate the effectiveness of these treatments beyond five years.
Recently in the New England Journal of Medicine, the FDA reviewed its concerns about duration of bisphosphonate use for achieving and maintaining protection against fracture while minimizing rare but serious adverse events associated with these drugs, such as atypical fractures, osteonecrosis of the jaw, esophageal cancer, and atrial fibrillation.4,5 The evidence is clear that bisphosphonate treatment for three or four years is effective in reducing vertebral and nonvertebral fractures in osteoporotic women, although the optimal duration of treatment remains controversial. In both NEJM articles and other recent reviews on bisphosphonate benefit–risk ratios, there seems to be a consensus emerging that drug holidays in high-risk patients may be associated with a greater risk of subsequent fractures, Dr. Miller said.6,7 “High risk” is defined as the preexistence of a low trauma fracture or a femoral neck T-score of -2.5 or lower.