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Jury's Out on Weekly vs. Monthly Bisphosphonates


 

WASHINGTON — With billions of dollars at stake and the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are emerging all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For the oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). And the answer depends on whom you ask, judging from four poster presentations.

Two studies involving researchers from Roche Laboratories Inc. (codeveloper of Boniva, along with GlaxoSmithKline) suggested that not only did women prefer once-monthly ibandronate but they were also more likely to persist with the drug than were those on once-weekly alendronate or risedronate.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and his colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate.

The unadjusted 9-month persistence rates were 41% for patients receiving monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy.

Monthly ibandronate users were 31% more likely to be persistent with therapy, compared with those on weekly alendronate or risedronate, after controlling for age, copay, comorbidities, and prescriptions greater than a 30-day supply. “After accounting for potential confounding factors, the increased likelihood of persistence reflects the independent effect of dosing frequency on patient persistence,” the researchers wrote.

In the second study, postmenopausal women were enrolled in a prospective, open-label study if they had been receiving once-weekly alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for a minimum of 3 months. The women were given once-monthly ibandronate (150 mg) for a period of 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging, and his colleagues.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. This questionnaire included four domains: convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction or less bother/lower frequency of side effects. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of the women preferred once-monthly ibandronate, whereas 8% preferred once-weekly therapy and 5% did not cite a preference. The remainder of patient responses were not evaluable. Overall, 70% of patients (1,087 out of 1,543) in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, compared with previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly ibandronate doses. Experience of stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy was associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies involving researchers from Merck & Co. Inc. (maker of Fosamax), once-monthly ibandronate seemed to offer no advantage in persistence over once-weekly alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research, Merck & Co. Inc., and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription drug information for more than 150 million unique patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new (index) prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. They were excluded if they had a prescription for any bisphosphonate during the 12 months before the index date, in order to focus only on newly treated patients. All of the women were followed for 1 year. They were considered persistent users if they did not have a therapy break of more than 30 days between the end of one prescription's supply and the beginning of the next.

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