ライフサイエンスコーパス: denosumab

1 CE in reducing the risks of SRE than monthly denosumab.

2 consistent with the known safety profile of denosumab.

3 l patients who received at least one dose of denosumab.

4 e patients who received at least one dose of denosumab.

5 by disruption of RANK-RANKL interaction with denosumab.

6 Hypocalcemia occurred more frequently with denosumab.

7 on in bone turnover markers was greater with denosumab.

8 ; hypocalcemia occurred more frequently with denosumab.

9 and no adverse reactions to the injection of denosumab.

10 phonates or newer targeted therapies such as denosumab.

11 n and more reasonable alternative to monthly denosumab.

12 ident three days after the administration of denosumab.

13 e compact bone erosion that was prevented by Denosumab.

14 xtension, in which all participants received denosumab.

15 RCA1-mutation carriers who were treated with denosumab.

16 al drugs, especially the bone antiresorptive denosumab.

17 zoledronic acid and the monoclonal antibody denosumab.

18 osis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39).

19 omly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or

20 andomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo.

21 oice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks.

22 ast cancer with evidence of bone metastases; denosumab 120 mg subcutaneously every 4 weeks, intraveno

23 Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidro

24 The analyses included 252 patients (132, denosumab; 120, placebo) with a baseline and at least on

25 acebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for

26 % [2.9]; teriparatide, 0.7% [2.7], p<0.0001; denosumab 2.5% [2.6], p=0.0011).

27 the teriparatide (0.8% [4.1], p=0.0007) and denosumab (2.1% [3.8], p=0.0238) groups, as did total-hi

28 rall survival did not differ between groups (denosumab, 43.9 [95% CI 40.1-not estimable] months vs pl

29 n the teriparatide (6.2% [4.6], p=0.0139) or denosumab (5.5% [3.3], p=0.0005) groups.

30 to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n = 127) every 6 months.

31 ents received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) i

32 whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneou

33 ly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously e

34 Adjuvant denosumab 60 mg twice per year reduces the risk of clini

35 ive 24 months of teriparatide (20 mg daily), denosumab (60 mg every 6 months), or both drugs.

36 e randomly assigned to treatment groups (716 denosumab, 716 placebo).

37 h zoledronic acid (a bisphosphonate) or with denosumab (a monoclonal antibody to RANK ligand) reduces

38 We assessed denosumab, a fully human anti-RANKL monoclonal antibody,

39 This study compared denosumab, a fully human monoclonal anti-receptor activa

40 This randomized study compared denosumab, a fully human monoclonal antibody against rec

41 We investigated the effects of denosumab, a fully human monoclonal antibody against rec

42 We investigated the ability of denosumab, a fully human monoclonal antibody against rec

43 Denosumab, a fully human monoclonal antibody to receptor

44 Denosumab, a fully human mononoclonal antibody to recept

45 onally, data demonstrated the superiority of denosumab, a RANK-ligand antagonist, compared to zoledro

46 to both received an additional 24 months of denosumab alone (combination to denosumab group).

47 Denosumab also consistently increased time to bone metas

48 Denosumab also reduced the risk of nonvertebral fracture

49 Denosumab also reduces risk for radiographic vertebral f

50 Denosumab also significantly delayed time to first bone

51 Denosumab (AMG 162), a fully human monoclonal antibody t

52 Denosumab, an anti-RANK ligand monoclonal antibody, sign

53 ble, including antiresorptive agents such as denosumab and bisphosphonates, as well as complementary

54 f adverse events were comparable between the denosumab and placebo groups.

55 Denosumab and radium-223 reduce the risk of skeletal-rel

56 ATA-Switch) is a preplanned extension of the denosumab and teriparatide administration study (DATA),

57 Denosumab and toremifene (a selective estrogen receptor

58 ypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo.

59 high-strength evidence that bisphosphonates, denosumab, and teriparatide reduce fractures compared wi

60 d haematology), and participant incidence of denosumab antibody formation.

61 dy, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 mont

62 porotic women switching from teriparatide to denosumab, bone mineral density continued to increase, w

63 Denosumab caused sustained suppression of markers of bon

64 andomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one o

65 e generally similar in patients treated with denosumab compared with those receiving placebo or alend

66 sphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active

67 Denosumab consistently improves BMFS in men with shorter

68 In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0

69 gs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as ad

70 by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bo

71 adverse events for all individuals receiving denosumab decreased from 165.3 to 95.9 per 100 participa

72 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none

73 inst RANKL-expressing malignant cells and as denosumab does not stimulate NK reactivity, we generated

74 Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14,

75 orts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and

76 to receive 20 mug teriparatide daily, 60 mg denosumab every 6 months, or both.

77 The data represent up to 10 years of denosumab exposure for women who received 3 years of den

78 ose who transferred from a previous study of denosumab for GCTB (cohort 3).

79 clinical data on the efficacy and safety of denosumab for the treatment of postmenopausal osteoporos

80 The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with h

81 Denosumab given subcutaneously twice yearly for 36 month

82 density was unchanged in the teriparatide to denosumab group (0.0% [95% CI -1.3 to 1.4]), whereas it

83 se of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group

84 ensity increased more in the teriparatide to denosumab group (6.6% [95% CI 5.3-7.9]) than in the deno

85 ensity increased more in the teriparatide to denosumab group (8.3% [95% CI 6.1-10.5]) and the combina

86 the greatest increase in the combination to denosumab group (8.6% [7.1-10.0]; p=0.0446 vs the teripa

87 3% [95% CI 6.1-10.5]) and the combination to denosumab group (9.1% [6.1-12.0]) than in the denosumab

88 The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was

89 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in th

90 n score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and signif

91 observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, an

92 ased by 2.8% (1.2-4.4) in the combination to denosumab group (p=0.0075 for the teriparatide to denosu

93 Differences between the combination to denosumab group and the teriparatide to denosumab group

94 he lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the p

95 n to denosumab group and the teriparatide to denosumab group did not differ significantly (p=0.67).

96 extension, similar to rates observed in the denosumab group during the first three years of the FREE

97 ared with the placebo group, patients in the denosumab group had a significantly delayed time to firs

98 identified more infections (n = 146) in the denosumab group than in the control group (n = 99).

99 eased by 5.5% and 7.6%, respectively, in the denosumab group versus placebo (P < .0001 at both time p

100 ratide group, p=0.30 for the teriparatide to denosumab group vs the combination to denosumab group, a

101 umab group (p=0.0075 for the teriparatide to denosumab group vs the combination to denosumab group; p

102 comparisons, p=0.13 for the teriparatide to denosumab group vs the denosumab to teriparatide group,

103 during the study, of which one death (in the denosumab group) was thought to be related to the study

104 paratide received denosumab (teriparatide to denosumab group), those originally assigned to denosumab

105 to teriparatide group vs the combination to denosumab group).

106 24 months of denosumab alone (combination to denosumab group).

107 to teriparatide group vs the combination to denosumab group).

108 4.9-21.8) in 27 women in the teriparatide to denosumab group, 14.0% (10.9-17.2) in 27 women the denos

109 14.0-18.0) in 23 women in the combination to denosumab group, although this increase did not differ s

110 ide to denosumab group vs the combination to denosumab group, and p=0.41 for the denosumab to teripar

111 [7.1-10.0]; p=0.0446 vs the teriparatide to denosumab group, p<0.0001 vs the denosumab to teriparati

112 , with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazar

113 , with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk

114 , with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazar

115 ide to denosumab group vs the combination to denosumab group; p=0.0099 for the denosumab to teriparat

116 reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group.

117 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the p

118 Patients who received denosumab had a decreased incidence of new vertebral fra

119 Discontinuing teriparatide and denosumab, however, results in rapidly declining bone mi

120 Both bisphosphonates and denosumab improve BMD in men with nonmetastatic prostate

121 Denosumab improved BMD and reduced the incidence of new

122 b exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (lon

123 placebo group and the efficacy and safety of denosumab in men with PSADT </= 10, </= 6, and </= 4 mon

124 ficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone me

125 and efficacy results from a phase 2 study of denosumab in patients with GCTB.

126 the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated

127 r primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abno

128 eived 3 years of placebo and transitioned to denosumab in the extension (crossover group).

129 ibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived

130 f monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metas

131 Combined teriparatide and denosumab increased BMD more than either agent alone and

132 In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased b

133 study showed that combined teriparatide and denosumab increased bone mineral density more than eithe

134 Denosumab is a fully human monoclonal antibody to the re

135 Denosumab is a fully human monoclonal IgG2 antibody that

136 Denosumab is a promising therapeutic agent for the manag

137 Denosumab is an investigational fully human monoclonal a

138 opausal women with low bone mineral density, denosumab is associated with a greater increase in bone

139 Denosumab is shown to support bone mineral density in ho

140 itor therapy, twice-yearly administration of denosumab led to significant increases in BMD over 24 mo

141 Data for adjuvant denosumab look promising but are currently insufficient

142 Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primar

143 Subcutaneous denosumab may be similar to IV BPs in suppressing bone t

144 Given its unique actions, denosumab may be useful in the treatment of osteoporosis

145 Denosumab may delay worsening of pain compared with bisp

146 in patients who received radium-223 without denosumab (median 13 months, 12-NA).

147 and in patients who received radium-223 plus denosumab (median NA, 15 months-NA) than in patients who

148 ted with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop.

149 These preliminary data suggest that denosumab might be an effective treatment for osteoporos

150 o serious or fatal adverse events related to denosumab occurred.

151 Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE

152 ed clinical trial which tested the effect of denosumab on bone mineral density, we assessed the impac

153 There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA

154 hase II study was to evaluate the effects of denosumab on structural damage in patients with rheumato

155 ents shortly after transplantation to either denosumab on top of standard treatment (calcium and vita

156 assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years.

157 randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 3

158 leted (zoledronic acid) or are currently in (denosumab) phase III trials.

159 leted (zoledronic acid) or are currently in (denosumab) phase III trials.

160 e incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655.

161 nosumab group), those originally assigned to denosumab received teriparatide (denosumab to teriparati

162 Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vert

163 Denosumab reduced the risk of hip fracture, with a cumul

164 As compared with placebo, denosumab reduced the risk of new radiographic vertebral

165 Denosumab reduces bone turnover markers and increases bo

166 Denosumab represents a new treatment option for patients

167 Denosumab represents a potential novel treatment option

168 ion and no requirement for renal monitoring, denosumab represents a potential treatment option for pa

169 th concomitant abiraterone, enzalutamide, or denosumab require confirmation in prospective randomised

170 ther Novartis or Amgen, the makers of ZA and denosumab, respectively.

171 cells with the clinically available RANKL Ab Denosumab resulted in enhanced NK cell anti-leukemia rea

172 Denosumab significantly increased bone-metastasis-free s

173 Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%,

174 originally assigned to teriparatide received denosumab (teriparatide to denosumab group), those origi

175 ection (cystitis) occurred more often in the denosumab than in the control group (51 vs 25 episodes i

176 Denosumab therapy was also associated with significant i

177 men treated with alendronate are switched to denosumab, there is an increase in bone mineral density

178 be substantially reduced by the addition of denosumab, this treatment should be considered for clini

179 Both bisphosphonates and denosumab, through different pathways of action, signifi

180 ter displayed similar capacity compared with denosumab to neutralize the effects of RANKL on osteocla

181 Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited st

182 ost hoc analysis reveals that treatment with denosumab to prevent bone loss in first-year kidney tran

183 lendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fract

184 ab group (6.6% [95% CI 5.3-7.9]) than in the denosumab to teriparatide group (2.8% [1.3-4.2], p=0.000

185 enosumab group (9.1% [6.1-12.0]) than in the denosumab to teriparatide group (4.9% [2.2-7.5]; p=0.044

186 One participant in the denosumab to teriparatide group had nephrolithiasis, cla

187 ation to denosumab group, and p=0.41 for the denosumab to teriparatide group vs the combination to de

188 ination to denosumab group; p=0.0099 for the denosumab to teriparatide group vs the combination to de

189 assigned to denosumab received teriparatide (denosumab to teriparatide group), and those originally a

190 paratide to denosumab group, p<0.0001 vs the denosumab to teriparatide group).

191 mab group, 14.0% (10.9-17.2) in 27 women the denosumab to teriparatide group, and 16.0% (14.0-18.0) i

192 s it decreased by -1.8% (-5.0 to 1.3) in the denosumab to teriparatide group, and increased by 2.8% (

193 r the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0.30 for the teripara

194 ontinued to increase, whereas switching from denosumab to teriparatide results in progressive or tran

195 de, p=0.0336 for combination to denosumab vs denosumab to teriparatide).

196 ]; p=0.0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0.0336 for combination to d

197 Overall, 74% of denosumab-treated patients (157 of 211) achieved a more

198 On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bis

199 Denosumab treatment for 12 months resulted in an increas

200 INTERPRETATION: Denosumab treatment for up to 10 years was associated wi

201 Results The mean costs of the denosumab treatment strategy are nine-fold higher than g

202 Bone turnover markers decreased with denosumab treatment.

203 to teriparatide, p=0.0336 for combination to denosumab vs denosumab to teriparatide).

204 4.9% [2.2-7.5]; p=0.0447 for teriparatide to denosumab vs denosumab to teriparatide, p=0.0336 for com

205 Denosumab was administered subcutaneously every 4 weeks

206 Denosumab was associated with increased bone mineral den

207 Denosumab was associated with tumour responses and reduc

208 While denosumab was found to reduce fractures, long-term survi

209 Denosumab was noninferior (trending to superiority) to Z

210 Denosumab was noninferior to ZA in delaying time to firs

211 Although directionally favorable, denosumab was not statistically superior to ZA in delayi

212 Denosumab was superior to zoledronic acid in delaying or

213 Denosumab was superior to zoledronic acid in delaying ti

214 Cabazitaxel, sipuleucel-T and denosumab were approved in 2010 by regulatory agencies i

215 cy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 4

216 assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of pos

217 We compared combined teriparatide and denosumab with both agents alone.