Nicole Mairon

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.

Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis

BACKGROUND An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20‐expressing B cells, in the primary progressive form of the disease. METHODS In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time‐to‐event analysis. RESULTS The percentage of patients with 12‐week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24‐week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25‐foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2‐weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain‐volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36‐Item Short‐Form Health Survey. Infusion‐related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections. CONCLUSIONS Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long‐term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann–La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570.)

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

BACKGROUND B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. METHODS In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta‐1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate. RESULTS The annualized relapse rate was lower with ocrelizumab than with interferon beta‐1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta‐1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium‐enhancing lesions per T1‐weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta‐1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper‐limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta‐1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion‐related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta‐1a. Neoplasms occurred in 0.5% of the patients treated with ocrelizumab and in 0.2% of those treated with interferon beta‐1a. CONCLUSIONS Among patients with relapsing multiple sclerosis, ocrelizumab was associated with lower rates of disease activity and progression than interferon beta‐1a over a period of 96 weeks. Larger and longer studies of the safety of ocrelizumab are required. (Funded by F. Hoffmann–La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333, respectively.)

PO128 Infusion-related reactions with ocrelizumab in rms and ppms

Background Infusion-related reactions (IRRs) have been observed with ocrelizumab treatment. Objective To evaluate the pattern of IRRs in studies of ocrelizumab in relapsing (OPERA I/II [NCT01247324/NCT01412333]) and primary progressive (ORATORIO [NCT01194570]) multiple sclerosis. Methods During the 96 week OPERA studies, patients received ocrelizumab 600 mg via intravenous (IV) infusion every 24 weeks or subcutaneous interferon beta-1a (IFNβ−1a) 44 µg three-times weekly. In ORATORIO, patients received ocrelizumab 600 mg IV given as two 300 mg infusions 14 days apart or matching placebo every 24 weeks for ≥120 weeks. Patients were pretreated with IV methylprednisolone 100 mg or blinded equivalent; analgesics/antipyretics and antihistamines were recommended. Results Safety analyses included patients from OPERA I/II (ocrelizumab, n=825; IFNβ−1a, n=826) and ORATORIO (ocrelizumab, n=486; placebo, n=239). Infusion-related reactions were more common with ocrelizumab versus comparator in OPERA I/II (34.3% vs 9.7% with IFNβ−1a) and ORATORIO (39.9% vs 25.5% with placebo), and were most frequent with the first infusion, decreasing thereafter. The majority of IRRs were mild to moderate in severity and most commonly included pruritus, rash, throat irritation and flushing. Conclusions The most common adverse event in these studies was IRRs, which were mostly mild to moderate in severity and decreased in incidence after the first infusion.