地舒单抗效果好吗？

It is a human immunoglobulin G2 (IgG2) monoclonal antibody with high specificity and affinity for RANKL. RANK receptor signaling promotes osteolysis and tumor growth. Desosumab inhibits tumor growth and reduces bone destruction by binding to RANKL and preventing it from activating RANK on the surface of osteoclasts, osteoclast precursors and osteoclast-like giant cells. Is denosumab effective?

A randomized, placebo-controlled Phase II clinical trial to evaluate the efficacy and safety of this product in the treatment of osteoporosis in postmenopausal women. Patients were randomly divided into 7 denosumab treatment groups [41 to 54 subjects in each group, respectively, subcutaneous injection of denosumab 6, 14, 30 mg (all once every 3 months), 14, 60, 100 or 210 mg (all once every 6 months)], an active control group (oral alendronate sodium 70 mg, once a week) and a placebo group. The main evaluation index is the change of the patient's spinal bone mineral density (BMD) from the baseline level after treatment. The results showed that after 12 months, compared with the baseline level, the spinal BMD of patients in the treatment group increased by 3.0% to 6.7%, that in the control group increased by 4.6%, and that in the placebo group decreased by 0.8% (P < 0.001). After 24 months, the spinal BMD of patients in the treatment group increased by 4.13% to 8.89%, while that in the placebo group decreased by 1.18%. The BMD of the hip and distal 1/3 of the radius in the treatment group was also significantly increased compared with the placebo. During this period, there were no significant differences in patient tolerability, BTM levels, and adverse reaction rates between groups. Among the 7 treatment groups, the 60 mg (once every 6 months) group has an ideal balance point in terms of safety and efficacy, and this dose will continue to be used in Phase III clinical trials in the future.

A 3-year randomized, double-blind, placebo-controlled phase III clinical trial FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) evaluated the efficacy and safety of denosumab in the treatment of osteoporosis in postmenopausal women. Patients were randomly assigned to: treatment (denosumab 60 mg subcutaneously every 6 months, n = 3902) or placebo (n = 3906). The primary outcome measure was the incidence of new vertebral fractures over the 3-year period, and secondary outcomes included the incidence of hip and nonvertebral fractures and the time to first fracture during the observation period. The subjects were aged between 60 and 90 years old, with an average age of 72.3 years. The basic value of spine or total hip T-score was between -4.0 and -2.5 (the average was -2.8). About 23% of the subjects had a history of at least one fracture before entering this trial. All patients also received daily supplements of 1,000 mg of vegetarian calcium and 400 to 800 IU of vitamin D. The results showed that compared with the placebo group, the incidence of new vertebral fractures in the treatment group was reduced by 68% (2.3% in the treatment group, 7.2% in the placebo group, P < 0.0001), the incidence of hip fractures was relatively reduced by 40% (0.7% in the treatment group, 1.2% in the placebo group, P = 0.036), and the incidence of non-vertebral fractures was relatively reduced. 20% (6.5% in the treatment group and 8.0% in the placebo group, P =0.011).

Another randomized, placebo-controlled phase III clinical trial, DEFEND (Denosumab Fortifies Bone Density), evaluated the role of denosumab in preventing osteoporosis in postmenopausal women. The average age of the subjects was 59.4 years old, and the spine T-scores were between -1.0 and -2.5 (the average was -1.61). They were randomly divided into a treatment group (denosumab 60 mg subcutaneous injection, once every 6 months, n = 166) or a placebo group (n = 166). All patients were supplemented with 1,000 mg of calcium every day, and the serum was passed through the subjects' plasma. The level of 25-hydroxyvitamin D determines the need for vitamin D supplementation. The main evaluation index is the change in spinal BMD measured by dual energy X-ray absorptiometry (DXA) compared with the baseline level. The results showed that after 24 months, denosumab significantly increased spinal BMD values ​​compared with placebo (a 6.5% increase in the treatment group versus a 0.6% decrease in the placebo group). In addition, the BMD values ​​of all tested parts such as the hip bone and distal radius in the treatment group increased significantly. At the same time, markers of bone resorption and formation were significantly reduced. The overall incidence of adverse reactions in the treatment group was similar to that in the placebo group during the observation period.

A one-year, double-blind, randomized controlled phase III clinical trial DECIDE (Determining Efficacy: Comparison of Initiating Denosumab versus alEndronate) compared the effectiveness and safety of this product and alendronate. A total of 1189 postmenopausal women were enrolled. The average baseline T-score of the lumbar spine of the enrolled patients was -2.6, and the average age was 64 years old. Patients were randomly divided into: treatment group (60 mg subcutaneous injection of this product, once every 6 months, n = 594), control group (oral alendronate sodium 70 mg, once every 6 months, n = 595). All subjects were supplemented with 500 mg of calcium per day, and the dose of vitamin D was adjusted based on plasma 25-hydroxyvitamin D levels. After 12 months, it can be observed that the BMD of both groups increased at all detection sites (hip, spine, femoral neck, trochanter, and distal 1/3 of the radius), but the increase in the treatment group was more significant than that of the control group (the primary endpoint of total hip BMD increased by 3.5 and 2.6, respectively, P <0. 000 1). The incidence of adverse reactions was similar between the two groups. A patient survey showed that the majority of patients (77%) preferred to receive subcutaneous injections twice a year.