In an analysis of fracture risk associated with loop diuretic use among postmenopausal women in the Women's Health Initiative (WHI) study, investigators demonstrated no significant association between loop diuretic use and fractures or changes in bone mineral density (BMD). With prolonged use of loop diuretics, however, the risk of fracture was modestly increased.
The Long-Term Intervention on Fractures with Tibolone (LIFT) study demonstrated a reduced risk of vertebral fracture, breast cancer, and possibly colon cancer but a significantly increased risk of stroke in older postmenopausal women treated with tibolone versus those treated with placebo.
The first phase of a double-blind, randomized, parallel-group, multicenter, outpatient study demonstrated that treatment with the combination of etanercept and methotrexate was more effective in inducing both clinical remission and radiographic nonprogression than methotrexate alone in patients with early moderate-to-severe rheumatoid arthritis (RA).
Tocilizumab, an investigational agent for the treatment of moderate-to-severe rheumatoid arthritis, is a humanized anti-IL-6 receptor monoclonal antibody. Because tocilizumab contains a mouse monoclonal antibody grafted onto human immunoglobulin, the grafted antibody is less antigenic and has a longer half-life than the mouse antibody. When administered, tocilizumab inhibits IL-6 activity by competing for both the membrane-bound and soluble types of IL-6 receptors, thus eliminating IL-6 transduction into the cell.
Drugs in development for the treatment of adult and juvenile rheumatoid arthritis
Treatment options for osteoporosis include calcium, vitamin D, estrogen plus progesterone, calcitonin, and bisphosphonates.
The use of biologic treatment for rheumatoid arthritis (RA) is associated with an increased risk of nonmelanotic skin cancer and melanoma, according to a large observational study published that included 13,001 patients.
A summary of agents in late-stage development for the prevention and/or treatment of osteoporosis.
In 2 prospective cohort studies published in the Archives of Internal Medicine, researchers demonstrated that selective serotonin-reuptake inhibitor (SSRI) use, but not the use of other common antidepressants, was associated with a significant decrease in total hip and lumbar spine bone mineral density (BMD) among older patients compared with nonuse of antidepressants.
In a large cohort study, it was demonstrated that the use of intravenous (IV) bisphosphonates was associated with an increased risk of inflammatory conditions or osteomyelitis of the jaw and the need for jaw or facial bone surgery.
A randomized, double-blind, placebo-controlled trial published in the Journal of the American Medical Association (JAMA) found that women who discontinued alendronate after 5 years demonstrated a moderate decline in bone mineral density (BMD) and a gradual increase in serum markers of bone turnover compared with women who continued taking alendronate for an additional 5 years, but mean levels among patients who discontinued therapy remained at or above baseline levels measured 10 years earlier. In addition, no greater fracture risk other than for clinically detected vertebral fractures was seen in the discontinuation group compared with patients who continued alendronate for 10 years.
Review of agents in late-stage development for the treatment of ankylosing spondylitis, osteoarthritis, and related pain (December 2006).
Review of agents in late-stage development for the treatment of juvenile idiopathic, psoriatic, and rheumatoid arthritis (November 2006).
TNF inhibitor approved for inhibiting joint damage, improving physical function in psoriatic arthritis
Disease-modifying antirheumatic drugs (DMARDs) reduce the risk of acute myocardial infarction (MI) in patients with rheumatoid arthritis (RA), according to results of an observational study published in the journal Arthritis & Rheumatism.
The selective estrogen-receptor modulator (SERM) raloxifene reduces the risks of invasive breast cancer and vertebral fracture in postmenopausal women but also increases the risks of venous thromboembolism and fatal stroke, a study in the New England Journal of Medicine (NEJM) concluded.
Abatacept (Orencia, Bristol-Myers Squibb) is the first T-lymphocyte co-stimulation modulator to be approved by FDA. The agent is indicated for use in patients with moderate-to-severe, active rheumatoid arthritis who have not had an adequate response to methotrexate, tumor necrosis factor (TNF) inhibitors, or other disease-modifying anti-rheumatic drugs (DMARDs).
A meta-analysis of 9 randomized, placebo-controlled studies of rheumatoid arthritis (RA) patients treated with the anti-tumor necrosis factor (anti-TNF) agents infliximab and adalimumab suggests an increased risk of malignancies dependent on dose and an increased risk of serious infections.
A matched-case control study comparing 378 Swedish patients with rheumatoid arthritis (RA) in whom malignant lymphoma developed with a control group of 378 RA patients who did not develop lymphoma found no observed association between lymphoma risk and various methods of RA treatment, according to an article in the journal Arthritis & Rheumatism.
Rheumatoid arthritis patients, hindered by an inadequate response to tumor necrosis factor-alpha (TNF-alpha) inhibitors, may find some relief in the form of a drug that belongs to a new class of selective costimulation modulators.
A pivotal phase 3 trial of a fully human monoclonal antibody, denosumab, that prevents bone destruction is under way and includes 7,800 postmenopausal, osteoporotic women aged 60 to 90 years. The primary endpoint is new vertebral fractures versus placebo and secondary end points are safety and tolerability of the new agent. Phase 2 clinical trials have demonstrated that denosumab is superior to aldendronate in preserving bone mineral density (BMD), reported researchers during the American College of Rheumatology Annual Scientific Meeting in San Diego, Calif.
This recombinant IgG1 monoclonal antibody exerts its therapeutic effect through inhibition of human tumor necrosis factor (TNF).
One year of bisphosphonate therapy maintains the gains in bone mineral density (BMD) experienced after 1 year of full-length parathyroid hormone (1–84) in postmenopausal women at risk of osteoporotic fracture. The findings were published in the New England Journal of Medicine (2005;353:555–565).
First once-monthly therapy approved for treatment and prevention of osteoporosis
A review of agents in late-stage development for the treatment of osteoporosis (March 2005)
