ライフサイエンスコーパス: belatacept

1 phenolate (MPA), sirolimus, tofacitinib, and belatacept.

2 d to assess long-term safety and efficacy of belatacept.

3 preexisting Tfh cells more efficiently than belatacept.

4 highest efficacy may be in combination with belatacept.

5 st (n = 25) T-cell subsets were sensitive to belatacept.

6 lso had early rejection before initiation of belatacept.

7 inal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious c

8 were 11.1%, 21.9%, and 13.9%, respectively (belatacept 4-weekly vs cyclosporine: HR = 1.06, 95% CI 0

9 tes from second randomization to year 10 for belatacept 4-weekly, belatacept 8-weekly, and cyclospori

10 Estimated mean GFR values at year 10 for belatacept 4-weekly, belatacept 8-weekly, and cyclospori

11 ar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and

12 orine: HR = 1.06, 95% CI 0.35-3.17, P = .92; belatacept 8-weekly vs cyclosporine: HR = 2.00, 95% CI 0

13 mization to year 10 for belatacept 4-weekly, belatacept 8-weekly, and cyclosporine were 11.1%, 21.9%,

14 R values at year 10 for belatacept 4-weekly, belatacept 8-weekly, and cyclosporine were 67.0, 68.7, a

15 mammalian target of rapamycin inhibitor) or belatacept (a high-affinity variant of the CD28 costimul

16 S after transplant using either abatacept or belatacept, a B7-1 blocker with higher affinity, and did

17 Belatacept, a B7-specific mediator of costimulation bloc

18 Belatacept, a second-generation, higher avidity variant

19 se of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, ma

20 eactive memory T cells that was resistant to belatacept alone.

21 Belatacept, an inhibitor of the CD28-CD80/86 costimulato

22 Belatacept, an investigational selective costimulation b

23 equencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12

24 stem using human T cells, the combination of belatacept and anti-LFA-1 was able to suppress cytokine

25 -59R; BENEFIT trial only); and (c) impact of belatacept and cyclosporine on side effect experience an

26 thway appeared to be sufficiently blocked by belatacept and did not predict rejection.

27 recipients included maintenance therapy with belatacept and mycophenolate mofetil plus induction with

28 seven liver transplant patients who received belatacept and mycophenolic acid maintenance immunosuppr

29 No patients who were treated with belatacept and one patient who was treated with CsA deve

30 Belatacept and sirolimus significantly prolonged rejecti

31 The combination of belatacept and sirolimus successfully prevents islet all

32 All received belatacept and sirolimus; six also received alefacept.

33 nty-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA compl

34 ismatched islet allotransplants treated with belatacept and the mTOR inhibitor, sirolimus.

35 ive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine.

36 The remaining agents (MPA, belatacept, and tofacitinib) had less apparent dose-depe

37 l, acute rejection rate was compared between belatacept- and tacrolimus-treated patients and immunolo

38 Belatacept appears to have similar longitudinal risk of

39 tacrolimus monotherapy together with monthly belatacept applications.

40 Abatacept and belatacept are clinically approved agents for the treatm

41 ss for evaluating efficacy and safety, using belatacept as an example.

42 xicity have made alternative agents, such as belatacept, attractive to clinicians.

43 evious analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyc

44 pating in studies comparing cyclosporine and belatacept-based immunosuppression.

45 Belatacept-based immunosuppressive therapy resulted in h

46 avored to develop a clinically translatable, belatacept-based regimen that could obviate the need for

47 At 2 years, belatacept-based regimens sustained better renal functio

48 data exist to directly compare outcomes with belatacept-based regimens to tacrolimus.

49 scharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens.

50 lymphocyte-associated antigen 4-Ig molecule belatacept (BEL), promote or inhibit the potential for i

51 regimens based on the costimulation blocker belatacept (BELA) or the antileukocyte functional antige

52 Understanding the extent to which belatacept binds to its targets in patients may enable c

53 vide the first direct clinical evidence that belatacept binds to one of its targets.

54 Belatacept blocks CD28-mediated T-cell costimulation and

55 selective inhibitor of T-cell costimulation, belatacept, blocks CD28-mediated T-cell activation by bi

56 the mean eGFR were significantly higher with belatacept (both the more-intensive regimen and the less

57 nificantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lym

58 Implementation of belatacept can be beneficial in hand transplantation.

59 The belatacept concentration associated with half-maximal re

60 Primary alloresponses were inhibited at the belatacept concentration required for CD86-receptor satu

61 od and dendritic cell cultures, although the belatacept concentrations required for CD86-receptor sat

62 Belatacept, currently enrolling phase III trials in rena

63 Belatacept (cytotoxic T-lymphocyte-associated protein 4

64 ded as a comprehensive summary of the entire belatacept data submission.

65 n our lead molecule MEDI5265, abatacept, and belatacept, depending on which type of APC was used, wit

66 CD86-receptor saturation correlated with belatacept dose/dose frequency and remained consistently

67 revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesti

68 n models were applied to participants in the Belatacept Evaluation of Nephroprotection and Efficacy a

69 cy as First-line Immunosuppression Trial and Belatacept Evaluation of Nephroprotection and Efficacy a

70 k profile versus cyclosporine A (CsA) in the Belatacept Evaluation of Nephroprotection and Efficacy a

71 stline Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy a

72 emonstrate application to 2 clinical trials: Belatacept Evaluation of Nephroprotection and Efficacy a

73 t-line Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy a

74 Patients received 5 mg/kg belatacept every 2 weeks, and the dosing interval was ex

75 eated patients were re-randomized to receive belatacept every 4 weeks (4-weekly, n = 62) or every 8 w

76 on was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 wee

77 were 2-fold higher in patients administered belatacept every 8 weeks vs every 4 weeks.

78 data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of rena

79 n, kidney transplant recipients treated with belatacept experienced increased rates of acute rejectio

80 argets in patients may enable correlation of belatacept exposure to receptor saturation as a pharmaco

81 mained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graf

82 the Biologics License Application (BLA) for belatacept for prophylaxis of organ rejection in adult p

83 tates--abatacept for autoimmune diseases and belatacept for transplantation.

84 In the belatacept group, four of five recipients developed seve

85 ft losses, due to rejection, occurred in the belatacept group.

86 to month 36, the mean cGFR increased in the belatacept groups by +1.0 mL/min/1.73 m(2) /year (MI) an

87 calculated glomerular filtration rate in the belatacept groups versus CsA.

88 roximately 21 mL/min/1.73 m(2) higher in the belatacept groups versus cyclosporine at year 3.

89 values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowe

90 D in each study between years 1 and 2 in the belatacept groups.

91 Belatacept has been associated with an increased acute r

92 Belatacept has been demonstrated to be as efficient as c

93 Long-term follow-up of recipients on belatacept has demonstrated superior glomerular filtrati

94 s targeting costimulatory molecules, notably belatacept, have made the progression from the bench, th

95 nsplant recipients with hepatitis C received belatacept immunosuppression in the perioperative period

96 the Food and Drug Administration approval of belatacept in 2011, the first approval of a maintenance

97 Acute rejection was more frequent with belatacept in BENEFIT.

98 nsitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant ce

99 The clinical profile of belatacept in kidney transplant recipients was evaluated

100 The success of belatacept in late-stage clinical trials inaugurates the

101 , high affinity variant of CTLA4-Ig, LEA29Y (belatacept), in a nonhuman primate model of islet transp

102 Focus on optimizing belatacept-inclusive regimens has led to studies using l

103 Belatacept is a biologic that targets CD80/86 and preven

104 Belatacept is a first-in-class co-stimulation blocker in

105 confidence interval [CI] 0.47-1.92; P = .89; belatacept less-intensive vs cyclosporine: HR = 1.61; 95

106 0%, and 25.8% for belatacept more-intensive, belatacept less-intensive, and cyclosporine, respectivel

107 to belatacept more-intensive-based (n = 74), belatacept less-intensive-based (n = 71), or cyclosporin

108 Understanding T-cell subset sensitivity to belatacept may identify cellular markers for immunosuppr

109 Belatacept may preserve the glomerular filtration rate a

110 a mammalian target of rapamycin inhibitor or belatacept) may demonstrate a better efficacy/safety pro

111 dose-dependent effects on interferon-gamma (belatacept median inhibition at 21.5%; P=0.004 vs. tacro

112 These results suggest that belatacept-mediated inhibition of alloresponses involved

113 s-intensive, and cyclosporine, respectively (belatacept more-intensive vs cyclosporine: hazard ratio

114 to year 10 were 22.8%, 37.0%, and 25.8% for belatacept more-intensive, belatacept less-intensive, an

115 ansplant recipients were first randomized to belatacept more-intensive-based (n = 74), belatacept les

116 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboon

117 uthorities for kidney transplant patients is belatacept (Nulojix), a fusion protein that interferes w

118 ive (MI) or a less intensive (LI) regimen of belatacept or a CsA-based regimen.

119 an intensive or a less-intensive regimen of belatacept or cyclosporine.

120 transplant recipients were 1:1 randomized to belatacept or tacrolimus combined with basiliximab, myco

121 more (MI) or less intensive (LI) regimen of belatacept, or cyclosporine.

122 ess susceptible to costimulatory blockade by belatacept, or resulted from incomplete CD80/86 blockade

123 table pharmacokinetics, and good safety with belatacept over 5 years.

124 ive was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute r

125 netic analyses showed consistent exposure to belatacept over time.

126 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less

127 ey-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen,

128 3 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the

129 tensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen.

130 th the more-intensive and the less-intensive belatacept regimens as compared with the cyclosporine re

131 ) increased over the 7-year period with both belatacept regimens but declined with the cyclosporine r

132 Thus far, no biomarker for belatacept-resistant rejection has been validated.

133 Belatacept's renal benefits were sustained, as evidenced

134 Belatacept saturated CD80 and CD86 receptors in whole bl

135 Here, we evaluate the belatacept sensitivity of allo-antigen-specific CD154-ex

136 undergoing alemtuzumab-induced depletion and belatacept/sirolimus immunosuppression were studied long

137 Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevent C

138 ed high patient persistence with intravenous belatacept, stable renal function, predictable pharmacok

139 igher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, an

140 opathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percen

141 There was one episode of graft rejection on belatacept therapy in a patient who had also had early r

142 d 90 days posttransplant and the duration of belatacept therapy ranged from 19 to 89 days.

143 and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand-transpla

144 regs can be combined in vitro with CTLA4-Ig (belatacept) to lead to enhanced inhibition of allo-proli

145 d by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals.

146 Whole blood from belatacept-treated patients had significantly lower leve

147 Belatacept-treated patients maintained a high rate of pa

148 Belatacept-treated patients reported better absolute PCS

149 Belatacept-treated patients tended to experience less si

150 At 3-6 months posttransplant, belatacept-treated patients were re-randomized to receiv

151 CD86 molecules on circulating monocytes in belatacept-treated patients were saturated at all timepo

152 Although 4 of 5 belatacept-treated patients with greater than 35 cells C

153 system PTLD--was observed more frequently in belatacept-treated patients.

154 ues of the biomarkers did not differ between belatacept-treated rejectors and nonrejectors.

155 The rejection incidence was higher in belatacept-treated than tacrolimus-treated 55% versus 10

156 FIT-EXT trial, the calculator estimated that belatacept use may result in reduction in MACE (>20%) an

157 orders occurred more frequently with CsA (2% belatacept versus 12% CsA).

158 ccurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders

159 n all-cause graft survival of less intensive belatacept versus cyclosporine at the second transplant

160 Compared with cyclosporine, belatacept was associated with improved HRQoL, suggestin

161 At 1 year, belatacept was associated with similar patient/graft sur

162 splant recipients with hepatitis C receiving belatacept was conducted under Institutional Review Boar

163 Belatacept was initially well tolerated in all cases.

164 Belatacept was initiated between 2 and 90 days posttrans

165 In the primary analysis, we found that belatacept was not associated with a statistically signi

166 Pharmacodynamic monitoring of belatacept was performed by measuring free CD86 on monoc

167 The primary indication for belatacept was perioperative renal dysfunction.

168 resistant cellular rejection occurring under belatacept was predominantly mediated by cytotoxic memor

169 A 61-year-old woman treated with belatacept, who received her first kidney transplant fro

170 A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acu

171 l--EXTended criteria donors trials comparing belatacept with cyclosporine in standard criteria donor

172 One patient is taking belatacept with lowered tacrolimus and sirolimus trough

173 this initial group of patients suggest that belatacept with mycophenolic acid may be a safe maintena

174 Kidney transplant patients treated with belatacept without depletional induction experience high