Data on long-term therapy with raloxifene HCl (Evista?, Eli Lilly and Company )for more than three years was published online in Current Medical Research & Opinion. Raloxifene is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM), which appears to act like estrogen in bone and to block the effects of estrogen in some tissues. It is an osteoporosis therapy for postmenopausal women that also reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis. Due to the chronic nature of osteoporosis and the risk of invasive breast cancer, raloxifene 60?mg/day (raloxifene) is intended to be used for long-term treatment (treatment >3 years).
The review includes summaries of previously published information, new, previously unpublished observations and new data on raloxifene use. The majority of available data came from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial and the Continued Outcomes of Raloxifene Evaluation (CORE) trial. In these trials, patients were evaluated for up to eight years. While available information is supportive of raloxifene use for more than three years, the optimum duration of raloxifene therapy is not known.
“Because of the chronic nature of postmenopausal osteoporosis and the risk of invasive breast cancer associated with the disease in postmenopausal women with osteoporosis, it is critical to evaluate medications that treat these conditions that require therapy over a prolonged period of time,” said lead author Robert Recker, M.D., professor of medicine, chief, division of endocrinology, director, Osteoporosis Research Center, Creighton University School of Medicine.
Use of raloxifene was evaluated by changes in vertebral fracture risk reduction, bone mineral density (BMD), markers of bone turnover, iliac crest bone biopsies, and invasive breast cancer risk reduction.
Vertebral fracture risk reduction
In the MORE trial, the relative risk reduction during the fourth year of the study was similar to the relative risk reduction during years zero to three.
Bone Mineral Density
Patients who stopped raloxifene therapy in the one-year period between the end of the MORE trial and the beginning of the CORE trial experienced a significant decrease in BMD. Once treatment resumed in the CORE trial, lumbar spine and femoral neck BMD increased in the raloxifene group.
In a previously unpublished analysis of data from the MORE study, patients who received raloxifene for three continuous years had lower bone resorption as measured by c-terminal telopeptide (CTX) values, with the average being similar to that found in premenopausal women. raloxifene is not for use in premenopausal women.
Iliac crest bone biopsies
Newly reported data from a subset of patients in the CORE trial included results of iliac crest biopsies in three patients treated with EVISTA for eight years. These iliac crest biopsies showed normal bone and bone cells and double label in all specimens.
Invasive breast cancer risk reduction
In a subset of postmenopausal women followed for up to eight years from randomization of the MORE trial to the end CORE, a reduction in the incidence of invasive breast cancer was observed in the raloxifene versus placebo group. The long term effects and the recommended length of therapy are not known.
Study safety findings
In clinical trials, patients in the raloxifene versus placebo group had higher incidence of venous thromboembolic events (blood clots in the legs, lungs or eyes), including deep vein thrombosis and pulmonary embolism, compared with patients who received placebo.
Raloxifene is contraindicated in women with active or past history of venous thromboembolism (VTE), including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis. The safety profile of raloxifene after four years of treatment was similar to that of raloxifene following three years of therapy.Additional adverse events (>2% and more common with EVISTA than with placebo) included hot flashes, leg cramps, swelling, flu-like symptoms, joint pain and sweating.
“Lilly is committed to providing information regarding our therapies to help healthcare professionals and their patients engage in more informed discussions about available treatment options for postmenopausal osteoporosis,” said co-author John Krege, M.D., medical fellow, Eli Lilly and Company.
“Long-term Raloxifene for Postmenopausal Osteoporosis” is a literature review of available information concerning raloxifene use for greater than three years for the treatment of postmenopausal osteoporosis and invasive breast cancer risk reduction in postmenopausal women with osteoporosis. Two reviewed studies were the Multiple Outcomes of Raloxifene Evaluation (MORE) trial and the Continued Outcomes of Raloxifene Evaluation (CORE) trial. The review includes summaries of previously published information, as well as a number of previously unpublished observations from analyses of the clinical study databases. In addition, new data from three patients who underwent iliac crest bone biopsies after eight years of raloxifene therapy were reported.
For more information:
– Recker RR, Mitlak BH, Ni X, Krege JH. Long-term raloxifene for postmenopausal osteoporosis. Curr Med Res Opin. 2011 Jul 25. [Epub ahead of print]
– Dickler MN, Norton L. The MORE trial: multiple outcomes for raloxifene evaluation–breast cancer as a secondary end point: implications for prevention. Ann N Y Acad Sci. 2001 Dec;949:134-42.
– Siris ES, Harris ST, Eastell R, Zanchetta JR, Goemaere S, Diez-Perez A et al. Skeletal effects of raloxifene after 8 years: results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res. 2005 Sep;20(9):1514-24. Epub 2005 May 16.