ライフサイエンスコーパス: tofacitinib

1 quality of life and patient preferences for tofacitinib.

2 ion of germinal centers of mice treated with tofacitinib.

3 second structurally unrelated Jak inhibitor, Tofacitinib.

4 developed in six patients who were receiving tofacitinib.

5 in patients who received placebo followed by tofacitinib.

6 erate to severe ulcerative colitis receiving tofacitinib.

7 greater response rates were observed in the tofacitinib 0.001% twice daily (27.3%), 0.005% twice dai

8 ring (CCC; 100%) at week 8 was greatest with tofacitinib 0.005% once daily (15.9%) versus vehicle (6.

9 The tofacitinib 0.005% once daily group showed significant i

10 HLA-DR was observed in patients treated with tofacitinib 0.005% QD and 0.003% BID: 71% and 67% of bas

11 n tears was 36% of baseline (P=0.053) in the tofacitinib 0.005% QD group and 95% of baseline (P > 0.2

12 , and IL-12p70, were markedly reduced in the tofacitinib 0.005% QD group but not the vehicle group.

13 at week 8 (40% of baseline, P=0.035) in the tofacitinib 0.005% QD group, whereas the vehicle group s

14 domized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg, 3 mg, 10 mg, or 15 mg, or placebo tw

15 Tofacitinib (0.0003% twice daily, n = 46; 0.001% in both

16 Patients received 1 of 5 doses of tofacitinib (0.0003%, 0.001%, 0.003%, or 0.005% twice da

17 ients were assigned randomly to groups given tofacitinib (0.5, 3, 10, or 15 mg twice daily) or placeb

18 facitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercep

19 itinib 5 mg group, 210 (63.6%) of 330 in the tofacitinib 10 mg group, 197 (58.8%) of 335 in the etane

20 itinib 5 mg group, 225 (68.2%) of 330 in the tofacitinib 10 mg group, 222 (66.3%) of 335 in the etane

21 329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, an

22 acitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etaner

23 (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg t

24 y assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks.

25 r 1 month of treatment were compared between tofacitinib (10 mg two times a day) and etanercept (50 m

26 s adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3

27 ne was significantly greater (P = 0.001) for tofacitinib 15 mg BID versus placebo.

28 For tofacitinib 15 mg BID, most patients reported satisfacti

29 = 507) were randomized to receive placebo or tofacitinib (20 mg/day, 1 mg twice daily, 3 mg twice dai

30 corded in 130 (39.5%) of 329 patients in the tofacitinib 5 mg group, 210 (63.6%) of 330 in the tofaci

31 hieved by 155 (47.1%) of 329 patients in the tofacitinib 5 mg group, 225 (68.2%) of 330 in the tofaci

32 curring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofaciti

33 Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitin

34 domly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h inte

35 ed them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg t

36 re randomly assigned (1:1:1) to receive oral tofacitinib (5 mg twice daily) monotherapy, oral tofacit

37 citinib (5 mg twice daily) monotherapy, oral tofacitinib (5 mg twice daily) plus methotrexate, or sub

38 ients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advan

39 or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily.

40 er among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among th

41 pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor.

42 ensitive to the cytokine-signaling inhibitor tofacitinib, a Janus kinase (JAK) inhibitor targeting JA

43 Tofacitinib, a novel, oral Janus kinase inhibitor, demon

44 n a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patient

45 progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decr

46 tofacitinib, and definite willingness to use tofacitinib again on the IBD PRTI at week 8.

47 Tofacitinib also inhibited the expression of IFN-gamma-i

48 erate to severe ulcerative colitis receiving tofacitinib, although at an individual level the agreeme

49 Tofacitinib, an oral Janus kinase inhibitor that targets

50 Tofacitinib, an oral Janus kinase inhibitor, is being in

51 Tofacitinib, an oral, small-molecule Janus kinase inhibi

52 CR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared wit

53 Tofacitinib and etanercept commonly reduced IL-6, CCL20,

54 se archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-se

55 e event rates over 12 weeks were similar for tofacitinib and etanercept.

56 ascular events occurred in five who received tofacitinib and in none who received placebo; as compare

57 ancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudic

58 Efficacy has been shown in phase III with tofacitinib and in phase II with fostamatinib and VX-509

59 alimumab and methotrexate (-6 [-14 to 3]) or tofacitinib and methotrexate (-8 [-16 to 1]).

60 INTERPRETATION: Tofacitinib and methotrexate combination therapy was non

61 Non-inferiority was declared for tofacitinib and methotrexate versus adalimumab and metho

62 monotherapy, 173 (46%) of 376 patients with tofacitinib and methotrexate, and 169 (44%) of 386 patie

63 nt (384 had tofacitinib monotherapy; 376 had tofacitinib and methotrexate; and 386 had adalimumab and

64 The results suggest that tofacitinib and other Janus kinase inhibitors may be eff

65 X-509 and fostamatinib; lipid elevation with tofacitinib and VX-509; creatinine elevation and anemia

66 The JAK inhibitors CP-690,550 (tofacitinib) and INCB018424 (ruxolitinib) have demonstra

67 tacrolimus, mycophenolate (MPA), sirolimus, tofacitinib, and belatacept.

68 xtreme satisfaction, definite preference for tofacitinib, and definite willingness to use tofacitinib

69 VX-509; creatinine elevation and anemia with tofacitinib, and hypertension and diarrhea with fostamat

70 The three compounds, roflumilast, tofacitinib, and ruxolitinib, were topically administere

71 trametinib, the Janus kinase-STAT inhibitor tofacitinib, and the STAT5 inhibitor pimozide reversed s

72 We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.

73 n = 384) were randomized to receive placebo, tofacitinib at 1, 3, 5, 10, or 15 mg administered orally

74 eks (total of 6 injections) followed by oral tofacitinib at 5 mg twice a day for 12 weeks.

75 ose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (10

76 io to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107

77 to MTX has been inadequate, the addition of tofacitinib at a dosage >/=3 mg twice daily showed susta

78 Treatment with tofacitinib at a dose of >/=3 mg twice a day resulted in

79 32%, 48%, 61%, and 78% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.39), 3 mg (P=0.55),

80 13%, 33%, 48%, and 41% of patients receiving tofacitinib at a dose of 0.5 mg (P=0.76), 3 mg (P=0.01),

81 Patients were randomly assigned to receive tofacitinib at a dose of 0.5 mg, 3 mg, 10 mg, or 15 mg o

82 eased at baseline but reduced after 1 day of tofacitinib (baseline, median of 1290 pSTAT1(+) cells/mu

83 kidney transplantation patients treated with tofacitinib/basiliximab (n=5), calcineurin inhibitor (CN

84 nsplantation patients, 7 days after starting tofacitinib/basiliximab treatment, cytokine-induced P-ST

85 Short-term treatment with tofacitinib BID was associated with dose-dependent impro

86 eneralized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor,

87 High tofacitinib concentrations were independently associated

88 f the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-m

89 range occurred in more patients who received tofacitinib continuously than in patients who received p

90 hemic stroke among the patients who received tofacitinib continuously.

91 This study indicates that in the future tofacitinib could provide a convenient and well-tolerate

92 nsive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibito

93 stigate how selective inhibition of JAK with tofacitinib (CP-690,550) affects osteoclast-mediated bon

94 gs targeting this pathway, the JAK inhibitor tofacitinib (CP-690,550) and the anti-interleukin (IL)-2

95 Tofacitinib (CP-690,550) is a novel oral Janus kinase in

96 Tofacitinib (CP-690,550) is a novel oral Janus kinase in

97 his study, we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways

98 One additional treatment may be tofacitinib (CP-690,550), an oral inhibitor of Janus kin

99 A new Janus kinase inhibitor, tofacitinib (CP-690550), has shown promising results for

100 This phase 1/2 study of tofacitinib demonstrated a trend for improving both sign

101 rom baseline for all tofacitinib groups, and tofacitinib demonstrated greater improvements than cyclo

102 Tofacitinib did not impact human osteoclast differentiat

103 Tofacitinib diminished the expansion and activation of m

104 cells with the Janus kinase (JAK) inhibitor tofacitinib disproportionately altered the expression of

105 Tofacitinib disrupted adventitial microvascular angiogen

106 20 response rates for patients receiving all tofacitinib dosages >/=3 mg twice daily (52.9% for 3 mg

107 ), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a bli

108 r placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53).

109 the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that swit

110 the placebo group that switched to the 10-mg tofacitinib dose.

111 eduction) from baseline was observed for all tofacitinib doses (-0.9 to -1.9) and vehicle (-2.0), but

112 tically significant (P<0.2, 2-sided) for all tofacitinib doses (1.7-3.1 mm), cyclosporine (3.9 mm), a

113 All tofacitinib doses were well tolerated, exhibiting better

114 In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo i

115 es of herpes zoster in patients who received tofacitinib during the trial.

116 Tofacitinib effectively suppressed innate and adaptive i

117 The JAK inhibitor tofacitinib effectively suppresses tissue-resident memor

118 assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placeb

119 All doses of tofacitinib exhibited a reasonable safety profile and we

120 oral compounds including kinase inhibitors (tofacitinib, fostamatinib, VX-509), an S1P lyase inhibit

121 ge in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib gro

122 .0001), and 71.9% (15 mg; P < 0.0001) in the tofacitinib group and 35.9% of patients in the adalimuma

123 ccurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib gro

124 sponse rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group

125 ia for an ACR 20 response (59.8% in the 5-mg tofacitinib group and 65.7% in the 10-mg tofacitinib gro

126 -mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0

127 eks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.

128 -mg tofacitinib group and 65.7% in the 10-mg tofacitinib group vs. 26.7% in the combined placebo grou

129 events occurring in >10% of patients in any tofacitinib group were diarrhea, upper respiratory tract

130 events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 7

131 the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in t

132 -mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo

133 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo g

134 losis developed in two patients in the 10-mg tofacitinib group.

135 ponse rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo gr

136 DI scores were greater in the 5-mg and 10-mg tofacitinib groups than in the placebo groups (-0.50 and

137 th 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the cr

138 se rates (month 6) were also superior in the tofacitinib groups versus placebo.

139 In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of

140 gnificant improvements from baseline for all tofacitinib groups, and tofacitinib demonstrated greater

141 placebo (5.6% and 8.7% in the 5-mg and 10-mg tofacitinib groups, respectively, and 4.4% with placebo;

142 creatinine levels had small increases in the tofacitinib groups.

143 Three patients treated with tofacitinib had an absolute neutrophil count of less tha

144 The remaining agents (MPA, belatacept, and tofacitinib) had less apparent dose-dependent effects on

145 Tofacitinib has a multitiered response in patients with

146 Tofacitinib improved disease control in patients with ac

147 phase 2 trial, we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely ac

148 nts still receiving placebo were switched to tofacitinib in a blinded fashion.

149 Herein we report the effects of tofacitinib in a murine model of GVHD.

150 We evaluated tofacitinib in patients with active psoriatic arthritis

151 We evaluated tofacitinib in patients with active psoriatic arthritis

152 chanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis.

153 tralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angio

154 Tofacitinib is a novel, oral, Janus kinase inhibitor tha

155 Tofacitinib is an oral Janus kinase inhibitor being inve

156 Tofacitinib is an oral Janus kinase inhibitor for the tr

157 Tofacitinib is an oral Janus kinase inhibitor that is un

158 Topical ophthalmic tofacitinib may act as an immunomodulator in patients wi

159 Tofacitinib may be an effective drug for treatment again

160 Tofacitinib may carry a significant risk for LTBI reacti

161 cause the increase of viral infections under tofacitinib may have been influenced by overlapping toxi

162 Tofacitinib monotherapy at >/=3 mg twice a day was effic

163 Two (1%) of the 384 patients receiving tofacitinib monotherapy died.

164 ference 2% [98.34% CI -6 to 11]) but not for tofacitinib monotherapy versus either adalimumab and met

165 n patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions i

166 Tofacitinib monotherapy was not shown to be non-inferior

167 s attained in 147 (38%) of 384 patients with tofacitinib monotherapy, 173 (46%) of 376 patients with

168 In total, 23 (6%) of 384 patients receiving tofacitinib monotherapy, 26 (7%) of 376 patients receivi

169 aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate,

170 1146 patients received treatment (384 had tofacitinib monotherapy; 376 had tofacitinib and methotr

171 Our goal was to characterize the impact of tofacitinib on LTBI using a mouse model of contained tub

172 current study was to determine the effect of tofacitinib on patient-reported outcomes (PROs).

173 is were randomized (3:1) to receive 10 mg of tofacitinib or placebo twice daily for 12 weeks.

174 ng inflamed human arteries were treated with tofacitinib or vehicle.

175 r patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events pe

176 ility to assess drug combinations other than tofacitinib plus methotrexate was limited.

177 notherapy, 26 (7%) of 376 patients receiving tofacitinib plus methotrexate, and 36 (9%) of 386 patien

178 arative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus metho

179 Oral administration of tofacitinib prevented GVHD-like disease manifested by we

180 kemic mice with the JAK3 selective inhibitor tofacitinib reduced the white blood cell count and cause

181 Our data indicate that tofacitinib reduces host containment of Mycobacterium tu

182 cular proteins significantly reduced only in tofacitinib responders.

183 ession, whereas the Janus kinase 3 inhibitor tofacitinib's success in the treatment of rheumatoid art

184 Compared with etanercept, tofacitinib showed a wider spectrum of cardiovascular bl

185 These results suggest that the JAK inhibitor tofacitinib suppresses osteoclast-mediated structural da

186 s than 2.6 was not significantly higher with tofacitinib than with placebo (5.6% and 8.7% in the 5-mg

187 Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosi

188 Adverse events were more frequent with tofacitinib than with placebo.

189 and herpes zoster infection were higher with tofacitinib than with placebo.

190 ction and serious infection were higher with tofacitinib than with placebo.

191 cle, we report that monotherapy of mice with tofacitinib (the JAK inhibitor) quells Ab responses to a

192 , double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis.

193 Tofacitinib therapy strongly inhibits gamma(c) cytokine-

194 Like tofacitinib, tocilizumab, a biologic targeting the IL-6

195 adverse events (AEs) in patients across all tofacitinib treatment arms (n = 272) were urinary tract

196 Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ p

197 Tofacitinib treatment was associated with elevations in

198 e normal Ig levels were still present during tofacitinib treatment, this agent specifically reduced a

199 orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a

200 ents); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients).

201 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or pl

202 thotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice dail

203 mly assigned, in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice dail

204 to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every

205 ly, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or placebo for 3 months followe

206 to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, placebo for 3 months followed b

207 or placebo for 3 months followed by 10 mg of tofacitinib twice daily.

208 a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still

209 TNF-alpha therapy are urgently required, and tofacitinib, vedolizumab and ustekinumab appear to be th

210 test elevation and neutropenia occurred with tofacitinib, VX-509 and fostamatinib; lipid elevation wi

211 More importantly, tofacitinib was also effective in reversing established

212 Tofacitinib was associated with an increase in both low-

213 received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.

214 phosphorylated STAT (P-STAT) 5 inhibition by tofacitinib was determined in cytokine-activated CD4(+)

215 Tofacitinib was equivalent to CsA in preventing acute re

216 ately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintena

217 ad an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 month

218 que psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice w

219 However, the safety profile of tofacitinib was poor, including increased incidences of

220 arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and wa

221 The efficacy of tofacitinib was superior to that of placebo at month 3 i

222 first such drug (the JAK inhibitor Xeljanz, tofacitinib) was approved by the FDA in November 2012 fo

223 erely active ulcerative colitis treated with tofacitinib were more likely to have clinical response a

224 uction, but the protein reduction effects of tofacitinib were strictly confined to treatment responde

225 nistration of the Janus kinase 2/3 inhibitor tofacitinib, which blocks IL-15 signaling.

226 Lesional T cells responded to tofacitinib with reduced proliferation rates (<10%) and