Denosumab in transfusion-dependent thalassemia osteoporosis: a randomized, placebo-controlled, double-blind phase 2b clinical trial
| Autor: | Dimitrios Christoulas, Ersi Voskaridou, Melpomeni Peppa, Evangelos Terpos, Athanasios Papaefstathiou, Maria N. Dimopoulou, Konstantina Repa, Ioannis Ntanasis-Stathopoulos, Athanasios Papatheodorou |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty Bone density Osteoporosis 030209 endocrinology & metabolism Placebo Gastroenterology Collagen Type I Drug Administration Schedule law.invention Bone remodeling 03 medical and health sciences 0302 clinical medicine Red Cells Iron and Erythropoiesis Randomized controlled trial Osteoprotegerin Double-Blind Method law Bone Density Internal medicine Medicine Humans Aged Bone mineral Bone Density Conservation Agents business.industry RANK Ligand Headache Hematology Middle Aged medicine.disease Placebo Effect Denosumab Treatment Outcome Thalassemia Female Bone Remodeling business Peptides 030215 immunology medicine.drug |
| Zdroj: | Blood advances. 2(21) |
| ISSN: | 2473-9537 |
| Popis: | Denosumab (DNM) is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL) that has been licensed for the treatment of different types of osteoporosis. However, the prospective data for the evaluation of DNM efficacy on transfusion-dependent thalassemia (TDT)–induced osteoporosis are rather limited. Thus, we conducted a randomized, placebo-controlled, double-blind, phase 2b clinical trial to evaluate DNM in TDT osteoporosis. Patients were assigned to receive either 60 mg DNM (n = 32) or placebo (n = 31) subcutaneously on day 0 and 180 during a total of 12 months of follow-up. The percentage increase of L1-L4 bone mineral density was higher in the DNM group than the placebo group (5.92% ± 5.25% vs 2.92% ± 5.56%, respectively; P = .043), whereas the advantage of DNM regarding wrist bone mineral density was much higher compared with placebo (−0.26% ± 5.31% vs −3.92% ± 8.71%, respectively; P = .035). No grade 3 or 4 toxicity was observed. DNM reduced pain scores that remained unaltered in the placebo group. DNM showed a significant reduction of soluble RANKL (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase between baseline and the 12th month (P < .01 for all comparisons) without changes in dickkopf-1, sclerostin, and osteocalcin. On the contrary, placebo patients showed an increase in sRANKL, osteoprotegerin, dickkopf-1, sclerostin, C-telopeptide of collagen type I, tartrate-resistant acid phosphatase isoform-5b, and bone-specific alkaline phosphatase during the study period (P < .01 for all comparisons). In conclusion, DNM increased lumbar spine and wrist bone mineral density and reduced pain and bone remodeling markers, and thus it is another valuable option for the management of TDT-induced osteoporosis. This trial was registered at www.clinicaltrials.gov as #NCT02559648. |
| Databáze: | OpenAIRE |
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