Update on monthly oral bisphosphonate therapy for the treatment of osteoporosis: focus on ibandronate 150 mg and risedronate 150 mg.
ABSTRACT Patient adherence to daily and weekly bisphosphonate treatments is poor and adversely affects their clinical outcome. To increase compliance, bisphosphonate therapies with longer dose-free intervals, such as oral once monthly, were developed.
The aim of this review is to provide a summary of the efficacy and safety of the two once-monthly oral bisphosphonates, ibandronate 150 mg and risedronate 150 mg. Fracture trials were initially performed with daily formulations, then bridging trials, in which the efficacy of intermittent dosing was assessed versus daily using validated surrogate endpoints for fracture. Two literature searches were carried out using the MEDLINE and BIOSIS online scientific citation database of published, peer-reviewed manuscripts up to and including December 2008.
The relative risk reduction (RRR) of new vertebral fractures with risedronate 5 mg daily was 41% (p = 0.003), and 49% (p < 0.001) versus placebo after 3 years in two Phase III studies. In patients at risk of incident fracture, the relative risk of non-vertebral fractures was significantly reduced by 39% (p = 0.02) with 5 mg risedronate versus placebo. In a post-hoc pooled analysis of 2.5 mg and 5 mg risedronate doses, also in patients at high risk of fracture, the relative risks of non-vertebral and hip fractures were significantly reduced by 20% (p = 0.03) and 30% (p = 0.02), respectively. In a Phase III study, the RRR of new vertebral fractures with 2.5 mg daily ibandronate was 62% (p = 0.0001) versus placebo after 3 years. Two pooled analyses of data from key randomised, double-blind, controlled trials with ibandronate dose levels consistent with 150 mg once-monthly reported significant RRRs in non-vertebral fractures of 38% (p = 0.038) and 30% (p = 0.041). In a bridging study, 150 mg once-monthly risedronate was non-inferior to 5 mg daily treatment for improvements in bone mineral density (BMD), but was significantly inferior for reductions in bone turnover markers (BTMs) (p < 0.05). Ibandronate 150 mg once monthly was superior to daily at 2 years in both surrogate marker measures, with significantly superior BMD gains reported at all sites (p < 0.05). In an extension of the bridging study, lumbar spine BMD progressively improved and previously reported femoral neck BMD gains were maintained with monthly ibandronate. Serum sCTX remained reduced within the premenopausal range.
Risedronate 150 mg once monthly has demonstrated less reduction of BTM and non-inferior BMD gains versus daily, whereas 150 mg once monthly ibandronate has demonstrated BTM suppression within the premenopausal range and BMD gains superior to the daily regimen. Furthermore, ibandronate has demonstrated antifracture efficacy with intermittent dosing in two pooled analyses. Risedronate has yet to demonstrate anti-fracture efficacy with an extended (intermittent) dosing regimen.
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ABSTRACT: The antifracture efficacy of ibandronate at vertebral and nonvertebral sites was assessed. A literature review of randomized phase III clinical trials, meta-analyses or observational studies that reported fracture endpoints or surrogate markers, and compared ibandronate with placebo or an active comparator. In a phase III study, 2.5 mg daily oral ibandronate reduced the incidence of new vertebral fractures versus placebo and the relative risk reduction (RRR) was sustained over 3 years (62%; p = 0.0001). In two bridging studies, oral ibandronate 150 mg once monthly and 3 mg quarterly intravenous (i.v.) were superior to oral 2.5 mg daily in producing bone mineral density (BMD) increases at all sites over 2 years (p < 0.05). These improvements were sustained over 5 years. In meta-analyses of pivotal ibandronate studies, doses equivalent to annual cumulative exposure (ACE) ≥ 10.8 mg (including 150 mg once monthly and 3 mg quarterly i.v.) significantly reduced the incidence of nonvertebral fractures versus placebo or ACE 5.5 mg (2.5 mg daily) (RRR 29.9% and 38%, respectively; p < 0.05). Therefore, prevention of nonvertebral fractures was found in all patients with the commercially available highest doses, and not only in high-risk patients as observed in randomized clinical trials with lower doses. Finally, a 12-month, observational study of claims databases reported comparable rates of nonvertebral fractures and a statistically significantly lower rate of vertebral fractures (p < 0.01) with ibandronate versus weekly bisphosphonates. A large body of evidence suggests that ibandronate has sustained vertebral and nonvertebral antifracture efficacy in women with postmenopausal osteoporosis.Therapeutic advances in musculoskeletal disease 04/2011; 3(2):67-79. DOI:10.1177/1759720X10395651
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ABSTRACT: The aim of this study was to assess the efficacy and safety of monthly oral 150 mg ibandronate in women with postmenopausal osteoporosis (PMO). A systematic review and meta-analysis were performed to determine treatment efficacy and safety outcomes between monthly oral 150 mg ibandronate and weekly 70 mg alendronate, daily 2.5 mg ibandronate, and a placebo. Eight randomized controlled trials were included in this systematic review and meta-analysis. Once-monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, showing increased bone mineral density (BMD) in both the lumbar spine and total hip. Pooled data from two cross-over trials showed that significantly more women with PMO preferred once-monthly ibandronate therapy to once-weekly alendronate therapy (relative risk [RR], 2.422; 95% confidence interval [CI], 2.111 to 2.825; p < 1 × 10(-8)) and found the monthly ibandronate regimen more convenient than the weekly alendronate regimen (RR, 3.096; 95% CI, 2.622 to 3.622; p < 1 × 10(-8)). Monthly 150 mg ibandronate therapy resulted in a significantly higher change in BMD of the lumbar spine than with the placebo. A once monthly 150 mg regimen produced greater increases in lumbar spine, total hip, femoral neck, and trochanter BMD than daily treatment, with a similar incidence of adverse events between the groups. Once monthly 150 mg ibandronate therapy was clinically comparable to weekly 70 mg alendronate, and patients strongly preferred the convenience of monthly ibandronate over weekly alendronate. Monthly 150 mg ibandronate was superior to, and as well tolerated as, the daily treatment.The Korean Journal of Internal Medicine 09/2011; 26(3):340-7. DOI:10.3904/kjim.2011.26.3.340
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ABSTRACT: Introduction: In this article, we have summarized the specific evidence on ibandronic acid (or ibandronate) efficacy, tolerability, and feasibility acquired from trials and clinical use. Areas covered: This critical review focuses on evidence from randomized controlled clinical trials, meta-analyses, surrogate markers, bridging trials, long-term extension studies, observational studies, clinical experiences in osteoporosis in addition to postmenopausal treatment adherence in clinical practice, and safety profile of ibandronic acid. Expert opinion: Pivotal studies on ibandronic acid efficacy in terms of antifracture effects on nonvertebral fractures had some intrinsic limitations. However, a large body of indirect evidence suggests that ibandronate has significantly sustained vertebral and nonvertebral antifracture efficacies in women with postmenopausal osteoporosis, in comparison to those observed with other nitrogen-containing bisphosphonates. Discrepancies in efficacy between the available bisphosphonate regimens appear to be a function of dose rather than to inherent differences in their respective therapeutic potential. Drugs or treatment regimens that minimize the risk of osteoporotic fractures and make the treatment of osteoporosis more convenient and suitable for patients are preferred: ibandronic acid marketed at oral doses of 150 mg once monthly and 3 mg quarterly as intravenous injection has these characteristics. The safety profile of ibandronic acid treatment appears to be good overall and in some cases better than that of other nitrogen-containing bisphosphonates.Expert Opinion on Pharmacotherapy 05/2013; DOI:10.1517/14656566.2013.795949 · 3.09 Impact Factor