ライフサイエンスコーパス: abatacept

1 dema, which were absent after treatment with abatacept.

2 bal assessment was seen only with 3 mg/kg of abatacept.

3 atigue) demonstrated a treatment effect with abatacept.

4 eived placebo during year 1 were switched to abatacept.

5 firming noninferiority of SC abatacept to IV abatacept.

6 5% CI 3.47-15.6) in C-peptide reduction with abatacept.

7 provements were significantly higher for the abatacept 10 mg/kg (P = 0.006) and 30/10 mg/kg (P = 0.02

8 ry analysis suggest the potential promise of abatacept 10 mg/kg for multiple sclerosis.

9 2 in the induction trials were randomized to abatacept 10 mg/kg or placebo every 4 weeks through week

10 % in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups

11 etes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1000 mg per dose) or placeb

12 e 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abata

13 1.4%, 19.0%, and 20.3% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical respon

14 7.2%, 10.2%, and 15.5% of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical respon

15 and 490 patients with UC were randomized to abatacept 30, 10, or 3 mg/kg (according to body weight)

16 ept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively.

17 tients were assigned to treatment groups (77 abatacept, 35 placebo).

18 monstrate mice treated with a single dose of abatacept 8 h post SEB exposure had reduced pathology co

19 Abatacept, a co-stimulatory blocker, and rituximab, a B

20 tement in the renal community, implying that abatacept, a costimulatory inhibitor that targets B7-1,

21 t as it can enable personalized therapy with abatacept, a CTLA-4 mimetic, and inform genetic counseli

22 tic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-im

23 Abatacept, a humanized version of CTLA4Ig, has been appr

24 BACKGROUND & AIMS: The efficacy of abatacept, a selective costimulation modulator, in Crohn

25 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patie

26 going National Institutes of Health trial of abatacept (Abatacept and Cyclophosphamide Combination: E

27 ercentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20

28 6 reactions occurred in 17 [22%] patients on abatacept and 11 reactions in six [17%] on placebo).

29 l of 118 patients were randomized to receive abatacept and 57 to receive placebo.

30 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatace

31 e randomized and treated, 86.2% receiving SC abatacept and 82% receiving SC adalimumab completed 12 m

32 Abatacept and belatacept are clinically approved agents

33 nal Institutes of Health trial of abatacept (Abatacept and Cyclophosphamide Combination: Efficacy and

34 e of costimulation through administration of abatacept and inhibitors of B7-related molecules and CD4

35 f adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but s

36 The abatacept and placebo groups exhibited similar frequenci

37 ding halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinica

38 Abatacept and rituximab were not associated with increas

39 In the SC abatacept and SC adalimumab groups, the incidence of ser

40 The results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in

41 head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along wit

42 s factor (TNF) inhibitors (TNFi), rituximab, abatacept and tocilizumab, following TNFi failure with n

43 as interleukin-6 antagonists (MRA), CTLA4Ig (abatacept), and anti-B cell therapy (rituximab) have alr

44 gle chain Fv (DC2219), belimumab, atacicept, abatacept, and abetimus sodium.

45 rankings between our lead molecule MEDI5265, abatacept, and belatacept, depending on which type of AP

46 reagents such as recombinant interleukin-10, abatacept, and CD3-specific antibodies are feasible as t

47 a treatment, the promising alternatives MRA, abatacept, and rituximab have been tested.

48 emulsions on the stability of BSA, lysozyme, abatacept, and trastuzumab formulations containing surfa

49 Abatacept- and vehicle-treated groups both maintained co

50 n, mice were treated for up to 16 weeks with abatacept, anti-murine TNF antibody, or vehicle.

51 were randomized at a ratio of 2:1 to receive abatacept ( approximately 10 mg/kg of body weight) or pl

52 se [ approximately 10 mg/kg] on day 1) or IV abatacept ( approximately 10 mg/kg) on days 1, 15, and 2

53 Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or pla

54 the TL and PASI scores were observed in all abatacept arms; a response according to the investigator

55 These results do not support the use of abatacept as a therapeutic strategy for targeting podocy

56 trials evaluated the efficacy and safety of abatacept as induction (IP) and maintenance (MP) therapy

57 Patients in the IM101075 trial received abatacept at 1 of 2 different dose regimens or placebo,

58 Abatacept at a dosage of 10 mg/kg elicited an increase i

59 Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weig

60 e randomized (1:1:1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg

61 CD and 131 patients with UC who responded to abatacept at week 12 in the induction trials were random

62 ns occurred in 3.8% of patients receiving SC abatacept compared to 9.1% of patients receiving SC adal

63 %), thus demonstrating the noninferiority of abatacept compared to adalimumab.

64 acept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months.

65 Patients taking abatacept continued to take it.

66 ry signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology.

67 patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid a

68 The selective costimulation modulator abatacept (CTLA-4Ig) binds to CD80 and CD86, blocking in

69 To describe the mechanisms of action of abatacept (CTLA4-Ig) and summarize the evidence of its e

70 Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treat

71 Abatacept (CTLA4-Ig), etanercept (anti-TNF), or phosphat

72 Abatacept (CTLA4-Ig), the first selective T-cell costimu

73 Abatacept (cytotoxic T-lymphocyte-associated antigen 4-i

74 The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid

75 g tissues from SEB-exposed mice treated with abatacept demonstrated significantly lower levels of IL-

76 Abatacept did not impair the ability of mice to control

77 hibition of CD28-mediated costimulation with abatacept does not seem to alter the inflammatory respon

78 in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening

79 The domains of abatacept exhibit different conformational stabilities t

80 ey are tailored for specific disease states--abatacept for autoimmune diseases and belatacept for tra

81 ), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%).

82 of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P

83 Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo gro

84 At 1 year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab group dem

85 ercent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respec

86 fidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the pla

87 Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1

88 ponses were also significantly higher in the abatacept group than in the placebo group (20.3 percent

89 x months, significantly more patients in the abatacept group than in the placebo group had a clinical

90 In the abatacept group, post hoc analysis demonstrated further

91 measures that best discriminated between the abatacept groups and placebo, and the sensitivities of t

92 trol group, compared to 22% and 24% in the 2 abatacept groups).

93 Subjects treated with abatacept had an increased percentage of naive and a cor

94 At 2 years, patients taking abatacept had maintained their responses on the American

95 Of these agents, only rituximab and abatacept have been evaluated in multiple sclerosis pati

96 However, abatacept in combination with biologic background therap

97 Abatacept in combination with MTX has the potential to p

98 Abatacept in combination with synthetic DMARDs was well

99 sing the same data set from a large trial of abatacept in lupus nephritis (IM101075).

100 sing data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which

101 oups and to further examine the potential of abatacept in lupus nephritis.

102 rationale for conducting further studies of abatacept in lupus nephritis.

103 of life, prevention of structural damage) of abatacept in patients with RA who have failed to respond

104 e of B7-1 immunostaining and the efficacy of abatacept in patients with recurrent FSGS after renal tr

105 We evaluated the effect of abatacept in recent-onset type 1 diabetes.

106 ls of IL-2 (p < 0.0001) after treatment with abatacept, indicating that T cell proliferation is the m

107 Abatacept induced partial or complete remissions of prot

108 Abatacept-induced antibodies occurred in 1.1% of SC abat

109 neficial effect continues after cessation of abatacept infusions.

110 R stimulation being associated with relative abatacept insensitivity.

111 Abatacept is a biologic developed for inflammatory arthr

112 Our findings demonstrate that abatacept is a robust and potentially credible drug to p

113 While the mechanism of action of abatacept is fundamentally different from that of anti-T

114 The studies showed that abatacept is not efficacious for the treatment of modera

115 Therefore, abatacept is not recommended for use in combination with

116 te reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)-treated patients (2.6%) and 18 IV

117 -cell activation using CTLA4-immunoglobulin (Abatacept), led to significant increases in survival dur

118 extracellular domain of CTLA4 (also known as abatacept, marketed as Orencia), demonstrated reduced le

119 Our data indicate that abatacept may stabilize beta1-integrin activation in pod

120 percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% i

121 Abatacept modulates co-stimulation and prevents full T-c

122 eceive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119).

123 y were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or pla

124 59% (95% CI 6.1-112) higher at 2 years with abatacept (n=73, 0.378 nmol/L) than with placebo (n=30,

125 therapies: mycophenolate mofetil, rituximab, abatacept, nilotinib, and fresolimumab.

126 trexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an

127 In addition, we did not detect an effect of abatacept on FEV1, provocative concentration of methacho

128 h year 1, suggesting an increasing effect of abatacept on the inhibition of structural damage in year

129 recurrent FSGS after transplant using either abatacept or belatacept, a B7-1 blocker with higher affi

130 randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28

131 Subjects were randomized 1:1 to receive abatacept or placebo, followed by a second allergen chal

132 Study patients received either abatacept or placebo, on a background of mycophenolate m

133 e and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 16

134 observed in animals treated with CTLA-4 Ig (abatacept) or CD28 blockade in the presence of anti-CTLA

135 nhibitor (tocilizumab) were either negative (abatacept) or were associated with high rates of adverse

136 nti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery.

137 We have studied abatacept (Orencia), a fusion protein that is constructe

138 Yet, despite continued administration of abatacept over 24 months, the decrease in beta-cell func

139 ed more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the othe

140 Abatacept produced significant clinical and functional b

141 on rates, consistent with the established IV abatacept profile.

142 SC abatacept provides efficacy and safety comparable with t

143 All abatacept regimens resulted in improved MRI, HAQ, and SF

144 ere the first biological agents, followed by abatacept, rituximab, and tocilizumab.

145 Abatacept's colloidal stability was studied by measuring

146 Abatacept's safety profile in combination with DMARDs al

147 V placebo)-treated patients (2.6%) and 18 IV abatacept (SC placebo)-treated patients (2.5%).

148 its TCR-driven activation, thereby promoting abatacept sensitivity.

149 as mice exposed to SEB and also treated with abatacept showed no weight loss for the duration of the

150 ontinuous 24-month costimulation blockade by abatacept significantly slows the decline of beta-cell f

151 Co-stimulation modulation with abatacept slowed reduction in beta-cell function over 2

152 Abatacept statistically significantly reduced disease ac

153 At 1 year, abatacept statistically significantly slowed the progres

154 anced the inhibition of T cell activation by abatacept, strongly inhibiting T cell activation driven

155 this study, we show that the extent to which abatacept suppresses T cell activation is influenced by

156 sults of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis

157 In patients treated with SC abatacept, the frequency of discontinuations due to AEs

158 For patients treated with 10 mg/kg abatacept, there were also statistically significant and

159 ransplantation, was rationally designed from abatacept to bind with more avidity to CD86, providing t

160 ell stimulation via the TCR, synergized with abatacept to inhibit T cell activation.

161 int for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients

162 -4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept.

163 as rheumatoid arthritis in combination with abatacept to promote the efficacy of treatment.

164 of subcutaneous forms of existing therapies (abatacept, tocilizumab), as well as newer-generation mon

165 In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BI

166 were 67.0% and 4.2%, respectively, in the SC abatacept-treated group and 65.2% and 4.9%, respectively

167 gen-induced eosinophilic inflammation in the abatacept-treated group compared with placebo (17.71% +/

168 and 65.2% and 4.9%, respectively, in the IV abatacept-treated group, with comparable frequencies of

169 ements were comparable between the SC and IV abatacept-treated groups.

170 % (95% confidence interval 72.6, 79.0) of IV abatacept-treated patients achieved an ACR20 response (e

171 pt-induced antibodies occurred in 1.1% of SC abatacept-treated patients and 2.3% of IV abatacept-trea

172 smallest detectable change) was 84.8% for SC abatacept-treated patients and 88.6% for SC adalimumab-t

173 Abatacept-treated patients had a similar incidence of ad

174 % (95% confidence interval 72.9, 79.2) of SC abatacept-treated patients versus 75.8% (95% confidence

175 SC abatacept-treated patients and 2.3% of IV abatacept-treated patients.

176 ertook this study to determine the effect of abatacept treatment in a murine model of chronic M tuber

177 function, and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of t

178 These changes were significantly affected by abatacept treatment, which drove the peripheral contract

179 Studies of a co-stimulation blocker (abatacept), tumor necrosis factor inhibitor (infliximab)

180 cells in rheumatoid arthritis was CTLA4-Ig (abatacept), use of this biologic is now expanding to oth

181 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 per

182 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 per

183 ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 per

184 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 per

185 8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 perc

186 0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 perc

187 increase in infections (32 [42%] patients on abatacept vs 15 [43%] on placebo) or neutropenia (seven

188 In CD-MP, 23.8% vs 11.1% of abatacept vs placebo patients were in remission at week

189 UC-MP, 12.5% vs 14.1% of patients receiving abatacept vs placebo were in remission at week 52.

190 transplant, treatment with the B7-1 blocker abatacept was associated with proteinuria remission.

191 Abatacept was associated with significant reductions in

192 Abatacept was found to be well tolerated and safe over t

193 ths, the decrease in beta-cell function with abatacept was parallel to that with placebo after 6 mont

194 The costimulation modifier abatacept was shown to be effective and relatively well

195 ing the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group m

196 lities that are highly pH dependent, whereas abatacept was weakly colloidally unstable at pH 6 or 7.5

197 neration, higher avidity variant of CTLA4Ig (abatacept), was approved by the Food and Drug Administra

198 were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both g

199 SC abatacept will provide additional treatment options, suc

200 ficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention ra