ライフサイエンスコーパス: belatacept

1 preexisting Tfh cells more efficiently than belatacept.

2 highest efficacy may be in combination with belatacept.

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

4 lso had early rejection before initiation of belatacept.

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

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

7 and tacrolimus, to 2 arms using maintenance belatacept.

8 protect kidney transplant recipients taking belatacept.

9 09 participants studied, 24 (4%) were taking belatacept.

10 re using ex vivo costimulatory blockade with belatacept.

11 pressive regimen, particularly tacrolimus or belatacept.

12 sets in vitro and in vivo in the presence of belatacept.

13 were breastfed while their mothers continued belatacept.

14 prove the selection of patients converted to belatacept.

15 d with 42 nonimmunized patients treated with belatacept.

16 activation subsequent to the introduction of belatacept.

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

18 e randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m

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

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

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

22 get of rapamycin inhibitors (144, 9.9%), and belatacept (58, 4.0%).

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

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

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

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

27 Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85

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

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

30 Belatacept, a B7-specific mediator of costimulation bloc

31 Belatacept, a second-generation, higher avidity variant

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

33 Belatacept, a selective T cell costimulation blocker, is

34 Literature evidence regarding belatacept, a selective T-cell costimulation blocker, du

35 kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, wo

36 CTLA-4 antibodies, including clinically used belatacept, abrogated irAEs without affecting cancer imm

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

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

39 Belatacept, an investigational selective costimulation b

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

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

42 -59R; BENEFIT trial only); and (c) impact of belatacept and cyclosporine on side effect experience an

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

44 In both the moderate intensity belatacept and low intensity belatacept groups, obese pa

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

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

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

48 didates were treated with the combination of belatacept and PI therapy, which significantly reduced b

49 underwent alemtuzumab induction followed by belatacept and sirolimus maintenance therapy.

50 Belatacept and sirolimus significantly prolonged rejecti

51 The combination of belatacept and sirolimus successfully prevents islet all

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

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

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

55 vival in CMV high-risk patients treated with belatacept and whether it is explained by the higher ris

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

57 lt, we stopped enrollment and treatment with belatacept, and all participants were treated with stand

58 itized animals were treated with bortezomib, belatacept, and anti-CD40 mAb twice weekly for a month (

59 belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transpla

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

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

62 Belatacept appears to have similar longitudinal risk of

63 tacrolimus monotherapy together with monthly belatacept applications.

64 Abatacept and belatacept are clinically approved agents for the treatm

65 After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control ar

66 Overall, 6 participants in the belatacept arm died compared with none in the control ar

67 equently, two additional participants in the Belatacept arm died for a total of five deaths compared

68 til, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept,

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

70 To report the first case of belatacept-associated multidrug-resistant Cytomegaloviru

71 Sirolimus was discontinued at day-180, and belatacept at day-365 posttransplant.

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

73 inhibition of PC generation with CTLA4-Ig or belatacept (B/B).

74 cipients Following Conversion to Nulojix(R) (Belatacept)-Based, NCT01820572.

75 lant recipients experiencing rejection under belatacept-based early corticosteroid withdrawal followi

76 ting induction in a recent randomized trial (Belatacept-based Early Steroid Withdrawal Trial, clinica

77 le data suggest that conversion from CNI- to belatacept-based immunosuppression >=6 mo posttransplant

78 enal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a

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

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

81 Belatacept-based immunosuppressive therapy resulted in h

82 trials have shown that, compared with CNIs, belatacept-based maintenance immunosuppression can impro

83 Belatacept-based maintenance immunosuppression is associ

84 mmunosuppression followed by conversion to a belatacept-based regimen can lower the AR risk while pre

85 the US Food and Drug Administration-approved belatacept-based regimen is also associated with higher

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

87 Belatacept-based regimens demonstrated promise across di

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

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

90 ation 16 (CTOT-16), sought to evaluate novel belatacept-based strategies employing tacrolimus and cor

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

92 l allograft rejection is more frequent under belatacept-based, compared with tacrolimus-based, immuno

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

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

95 using a conditioning regimen with aCD40 and belatacept (Bela).

96 transplant recipients converted from CNI to belatacept between 7/1/12 to 9/30/17.

97 transplant recipients converted from CNI to belatacept between July 1, 2012, and September 30, 2017.

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

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

100 Belatacept blocks CD28-mediated T-cell costimulation and

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

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

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

104 Implementation of belatacept can be beneficial in hand transplantation.

105 The belatacept concentration associated with half-maximal re

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

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

108 Belatacept confers increased patient and graft survival

109 nal transplant recipients were randomized to belatacept conversion ( n =223) or CNI continuation ( n

110 alvage immunosuppressive therapies, isolated belatacept conversion alone was associated with stabiliz

111 al experience with a prospective protocol of belatacept conversion in patients with chronic active an

112 In the belatacept conversion versus CNI continuation groups, 8%

113 r transplantation and were followed up after belatacept conversion, for a median of 308 days (interqu

114 After belatacept conversion, one antibody-mediated rejection w

115 Belatacept could be the treatment of choice in renal-tra

116 decades ago, resulted in the development of belatacept CTLA-4 fused with an immunoglobulin Fc domain

117 Belatacept, currently enrolling phase III trials in rena

118 Belatacept (cytotoxic T-lymphocyte-associated protein 4

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

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

121 s to counsel female transplant recipients on belatacept desiring to pursue pregnancy.

122 Costimulation blockade with belatacept did not provide sufficient immunosuppression

123 Neither rapamycin nor belatacept directly inhibited these cells.

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

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

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

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

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

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

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

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

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

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

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

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

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

137 The group receiving carfilzomib and belatacept exhibited significantly reduced levels of don

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

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

140 nergism between PI based desensitization and belatacept facilitating transplantation with a negative

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

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

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

144 clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs

145 ts with BMI >30 kg/m(2) in the low intensity belatacept group experienced significantly more rejectio

146 One patient in the belatacept group had post-transplant lymphoproliferative

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

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

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

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

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

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

153 erate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m(2) e

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

155 In kidney transplantation, Belatacept has been associated with a lower incidence of

156 Belatacept has been associated with an increased acute r

157 Belatacept has been demonstrated to be as efficient as c

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

159 Every 2-month (q2m) belatacept has potential to increase utilization, theref

160 Evidence indicates that patients on belatacept have lower rates of DSA formation, suggesting

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

162 who reject versus those who remain stable on belatacept identified three potential "risky" memory T c

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

164 ure, kidney transplant recipients treated by belatacept immunosuppression may be at increased risk fo

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

166 spectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal

167 Acute rejection was more frequent with belatacept in BENEFIT.

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

169 We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients

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

171 biting alloimmune responses, clinical use of belatacept in kidney transplantation revealed a substant

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

173 lower incidence of DSA, but experience with Belatacept in lung transplantation is limited.

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

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

176 alian target of rapamycin [mTOR] inhibitors, belatacept, induction agents, and withdrawal of calcineu

177 ths post-transplantation; 8 received monthly belatacept infusions.

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

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

180 Belatacept is potent in inhibiting B/T cell interaction,

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

182 0%, and 25.8% for belatacept more-intensive, belatacept less-intensive, and cyclosporine, respectivel

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

184 Five-year graft survival in the belatacept-less intensive arm was significantly higher t

185 In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White r

186 Although rejection was not uniform in the belatacept maintenance therapy groups, the frequency of

187 4 variants and that the clinically available belatacept may emerge as a broadly applicable drug to ab

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

189 Belatacept may impair humoral immunity, impacting the ef

190 Belatacept may preserve the glomerular filtration rate a

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

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

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

194 Patients were offered weaning to belatacept monotherapy after 1 year and followed for 5 y

195 h CoB, and permits control of rejection with belatacept monotherapy in selected patients.

196 Twelve patients were successfully weaned to belatacept monotherapy.

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

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

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

200 while prior work has shown that concomitant belatacept + mTOR inhibitor therapy is effective for mai

201 gh day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for th

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

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

204 imus, and T-cell costimulation blockade with belatacept) offer potential for enhanced benefits.

205 The impact of belatacept on CMV infection remains understudied.

206 In this study, we assessed the impact of belatacept on patient and graft survivals.

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

208 ppression were randomized (1:1) to switch to belatacept or continue treatment with their established

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

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

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

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

213 tient, or graft survival after conversion to belatacept over 5 years among HS and non-HS recipients.

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

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

216 netic analyses showed consistent exposure to belatacept over time.

217 Belatacept partially inhibited T-cell proliferation with

218 After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared

219 After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared

220 e CMV high-risk group, patients treated with belatacept presented a higher incidence of CMV viremia,

221 Alemtuzumab induction with belatacept/rapamycin-based maintenance immunotherapy (AB

222 es were collected from 8 patients undergoing belatacept-refractory rejection (BRR).

223 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less

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

225 3 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the

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

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

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

229 ns intended to further mitigate AR risks and belatacept-related outcomes in special populations, such

230 The cause of belatacept-resistant graft rejection was allocated to el

231 epresent a new therapeutic target to inhibit belatacept-resistant rejection during transplantation.

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

233 ory T cell subsets that potentially underlie belatacept-resistant rejection: CD4(+) CD28(+) T(EM) , C

234 Belatacept results in improved kidney transplant outcome

235 Belatacept's renal benefits were sustained, as evidenced

236 Belatacept saturated CD80 and CD86 receptors in whole bl

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

238 Conversion from CNI to belatacept should be done cautiously in high immunologic

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

240 Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevent C

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

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

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

244 scue" therapy for rejections occurring under belatacept that are refractory to traditional antireject

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

246 Every 2-month belatacept therapy may facilitate long-term utilization

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

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

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

250 desensitization with costimulation blockade (belatacept) to mitigate germinal center (GC) responses m

251 rfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four cont

252 Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged g

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

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

255 Belatacept-treated patients maintained a high rate of pa

256 Belatacept-treated patients reported better absolute PCS

257 Belatacept-treated patients tended to experience less si

258 gative recipients, 168 CMV high-risk and 203 belatacept-treated patients were included.

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

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

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

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

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

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

265 was halted early because of rejection in the belatacept treatment groups.

266 to optimize the many variables applicable to belatacept treatment, particularly for different patient

267 ective in lowering the AR risk compared with belatacept use in the de novo setting or conversion <6 m

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

269 Belatacept use was associated with 16.7-fold lower odds

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

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

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

273 line characteristics were similar for KTR on belatacept versus other regimens; the number of clinic v

274 cidence and persistence of CMV viremia under belatacept vs tacrolimus were compared.

275 Belatacept was a risk factor for PCP, possibly by increa

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

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

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

279 Belatacept was initially well tolerated in all cases.

280 Belatacept was initiated between 2 and 90 days posttrans

281 Every 2-month belatacept was noninferior to q1m, as the difference in

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

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

284 The primary indication for belatacept was perioperative renal dysfunction.

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

286 In parallel, belatacept was stopped and switched to tacrolimus.

287 Patients on belatacept were randomly assigned to q1m or q2m therapy.

288 Alemtuzumab and belatacept were well tolerated, but 44% of patients disc

289 The efficacy and safety of belatacept when converted from calcineurin inhibitors (C

290 The efficacy and safety of belatacept when converted from calcineurin inhibitors (C

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

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

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

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

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

296 our desensitized animals received additional belatacept with tacrolimus-based immunosuppression.

297 ng low-dose CNI plus costimulation blockade (belatacept) with intended CNI withdrawal (n = 22).

298 ival was lower in HS recipients converted to belatacept within the first year post transplant.

299 ival was lower in HS recipients converted to belatacept within the first-year posttransplant.

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