Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study.

OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing

Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-year results from the MOBILE study

Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year.Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of &gt;2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens.Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly.Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated.Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.<br/