ライフサイエンスコーパス: fingolimod

1 ibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod).

2 ften switch therapy to either natalizumab or fingolimod.

3 ly preceding switch to either natalizumab or fingolimod.

4 ent, interferon beta, glatiramer acetate, or fingolimod.

5 nth follow-up period after the initiation of fingolimod.

6 ts during the WP and after the initiation of fingolimod.

7 at clinically relevant therapeutic doses of fingolimod.

8 The patients were clinically stable on fingolimod.

9 iosis for 12 days with CYM-5442, vehicle, or fingolimod.

10 erse events shifted towards that typical for fingolimod.

11 tential and mechanisms of neuroprotection by fingolimod.

12 ed (1:1) to receive either 0.5 mg or 1.25 mg fingolimod.

13 fect of delaying the start of treatment with fingolimod.

14 efficacy after switching from IFNbeta-1a to fingolimod.

15 25 mg and 133 to placebo in cohort 1; 336 to fingolimod 0.5 mg and 354 to placebo in cohort 2).

16 53 (15%) of 358 patients given fingolimod 0.5 mg and 45 (13%) of 355 patients given pla

17 sisted of 336 patients randomly allocated to fingolimod 0.5 mg and 487 to placebo.

18 esults are presented here for the continuous-fingolimod 0.5 mg and pooled IFN-switch groups.

19 Fingolimod 0.5 mg caused more of the following adverse e

20 Fingolimod 0.5 mg is associated with a low incidence of

21 Mean PBVC was -0.86 (SD 1.22) for fingolimod 0.5 mg versus -1.28 (1.50) for placebo (treat

22 1), corresponding to a reduction of 48% with fingolimod 0.5 mg versus placebo.

23 isability progression (hazard rate 0.83 with fingolimod 0.5 mg vs placebo; 95% CI 0.61-1.12; p=0.227)

24 e study (EOS), ARR in patients on continuous-fingolimod 0.5 mg was significantly lower than in the IF

25 patients: 370 to fingolimod 1.25 mg, 358 to fingolimod 0.5 mg, and 355 to placebo.

26 sing-remitting multiple sclerosis-to receive fingolimod 0.5 mg, fingolimod 1.25 mg, or placebo orally

27 patients were switched in a masked manner to fingolimod 0.5 mg, whereas those on placebo continued on

28 n onwards, patients were assigned to receive fingolimod 0.5 mg/day or placebo (cohort 2).

29 acebo and 0.21 (0.17-0.25) in patients given fingolimod 0.5 mg: rate ratio 0.52 (95% CI 0.40-0.66; p<

30 S study demonstrated significant benefits of fingolimod 0.5 or 1.25 mg over interferon beta-1a (IFNbe

31 as performed before and after treatment with fingolimod (0.3 mg/kg/d by mouth, 28 d) or vehicle as a

32 Patients randomised to fingolimod (0.5/1.25 mg) in the core phase continued the

33 Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta fo

34 terferon beta (0.98 [0.65-1.49], p=0.93) and fingolimod (0.50 [0.25-1.01], p=0.18), and a lower proba

35 time curve) differed between natalizumab and fingolimod (-0.12 vs 0.04 per year, respectively, p < 0.

36 postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-y

37 infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipie

38 significantly lower in both groups receiving fingolimod--0.20 (95% confidence interval [CI], 0.16 to

39 tween Sept 3, 2008, and Aug 30, 2011 (147 to fingolimod 1.25 mg and 133 to placebo in cohort 1; 336 t

40 Patients were initially assigned to fingolimod 1.25 mg per day or placebo (cohort 1); howeve

41 On Nov 12, 2009, all patients assigned to fingolimod 1.25 mg were switched to the 0.5 mg dose in a

42 and randomly allocated 1083 patients: 370 to fingolimod 1.25 mg, 358 to fingolimod 0.5 mg, and 355 to

43 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared wi

44 iple sclerosis-to receive fingolimod 0.5 mg, fingolimod 1.25 mg, or placebo orally once daily (1:1:1;

45 el of AD, the 5xFAD model, with two doses of fingolimod (1 and 5 mg/kg/day) and measured the response

46 Fingolimod (1) is the first approved oral therapy for th

47 ratio [HR] 0.66 [95% CI 0.36-1.22], p=0.37), fingolimod (1.27 [0.60-2.70], p=0.67), and natalizumab (

48 nburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fin

49 ituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea

50 od 19%), yielding a total cohort of N = 256 (fingolimod 55%).

51 n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umea, n = 36, fingolimod 19%), yielding

52 A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for t

53 Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist

54 the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier.

55 Recently fingolimod, a functional S1P1 receptor antagonist, was i

56 Fingolimod, a nonselective sphingosine-1-phosphate (S1P)

57 Fingolimod, a sphingosine-1-phosphate receptor agonist,

58 syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue

59 at can also be activated in vivo by systemic fingolimod administration.

60 It is unknown whether fingolimod affects microglial activation in MS.

61 atients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (fem

62 neurons, underlie the beneficial effects of fingolimod after stroke.

63 ts given to MS patients: they are reduced by fingolimod, alemtuzumab, and dimethyl fumarate, whereas

64 fficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone

65 Fingolimod also decreased GFAP staining and the number o

66 Fingolimod also decreased infarct size in a rat model of

67 Fingolimod also readily penetrates the CNS, and fingolim

68 FTY720 (fingolimod), an FDA-approved drug for treatment of multi

69 erosis (MS)-like lesion after treatment with fingolimod, an established MS therapy.

70 tudy examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate an

71 Fingolimod, an oral sphingosine 1-phosphate receptor mod

72 sing fingolimod treatment using search terms fingolimod and either rebound or reactivation.

73 Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse act

74 Fingolimod and natalizumab therapies efficiently targete

75 had occurred in 232 and 338 patients in the fingolimod and placebo groups, respectively, resulting i

76 gs expand knowledge of the safety profile of fingolimod and strengthen evidence for its beneficial ef

77 ts given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab.

78 fectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsi

79 ffect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment

80 dings substantiate the beneficial profile of fingolimod as a disease-modifying agent in the managemen

81 s support a strong therapeutic potential for fingolimod as an acute rescue therapy for the treatment

82 The initial randomisation and dose of fingolimod assigned for the extension remained masked to

83 Fingolimod at 1 mg/kg/day provided better neuroprotectio

84 at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or i

85 In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon b

86 t study reveals that when applied topically, fingolimod attenuates both immediate and late-phase resp

87 The patients were switched to fingolimod because of safety reasons or therapy escalati

88 ants were included if they stopped receiving fingolimod between January 2014 and December 2015.

89 Importantly, fingolimod blocked the 2 activation events evoked in ast

90 Importantly, the treatment effect of fingolimod can be monitored in vivo by measuring the deg

91 Rates of VZV infections in fingolimod clinical trials are based on pooled data from

92 rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patie

93 on beta-1a, ARR was lower after switching to fingolimod compared with the previous 12 months (interfe

94 infection was higher for patients receiving fingolimod compared with those receiving other disease-m

95 patients switched from interferon beta-1a to fingolimod, continuous treatment with fingolimod for 2 y

96 Furthermore, fingolimod decreased interstitial fibrosis, cardiomyocyt

97 In mice at 3 months of age, we found that fingolimod decreased plaque density as well as soluble p

98 Fingolimod did not protect primary neurons against gluta

99 The anti-inflammatory effects of fingolimod did not slow disease progression in primary p

100 the group that received the 1.25-mg dose of fingolimod: disseminated primary varicella zoster and he

101 On withdrawal of fingolimod, drug-induced remission was lost and recrudes

102 ngosine-1-phosphate receptor activation with fingolimod during acute MI reduced infarct size via the

103 ngosine-1-phosphate receptor activation with fingolimod during acute myocardial infarction (MI) inhib

104 Furthermore, fingolimod efficacy in blocking astrocyte-mediated neuro

105 The Enquete Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a sur

106 More importantly, fingolimod enhanced neurobehavioral recovery.

107 In conclusion, fingolimod exerts protective effects in a mouse model of

108 -1a to fingolimod, continuous treatment with fingolimod for 2 years provides a sustained treatment ef

109 Three percent stopped fingolimod for efficacy, tolerance, or compliance issues

110 Each patient received treatment with oral fingolimod for various durations.

111 gosine 1-phosphate receptor (S1PR) modulator fingolimod (FTY720) ameliorated chronic progressive expe

112 Treatment with fingolimod (FTY720) during the late phase of disease rev

113 Recently, the S1P analogue Fingolimod (FTY720) has been approved for the treatment

114 The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients resul

115 Fingolimod (FTY720) is a sphingosine 1-phosphate (S1P) r

116 Fingolimod (FTY720) is an FDA-approved therapeutic drug

117 Recent studies have shown that fingolimod (FTY720) is neuroprotective in CNS injury mod

118 ssessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-

119 with either sphingosine kinase inhibitor or fingolimod (FTY720) significantly attenuated histamine-i

120 Importantly, fingolimod (FTY720), a S1P analog recently approved for

121 tudy was designed to determine the impact of fingolimod (FTY720), a sphingosine-1-phosphate receptor

122 Fingolimod (FTY720), a sphingosine-1-phosphate-receptor

123 hingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced

124 (+) gammadeltaT17 cells egress from LNs in a fingolimod (FTY720)-sensitive manner and use C-C chemoki

125 FTY720 (Fingolimod, Gilenya) is a sphingosine analog used as an

126 nd Drug Administration-approved drug FTY720 (fingolimod, Gilenya) or vehicle control solution from 5

127 events occurred in 84 (25%) patients in the fingolimod group and 117 (24%) in the placebo group, inc

128 The fingolimod group had a lower mean annualized relapse rat

129 7.2% (95% CI 71.87-82.51) of patients in the fingolimod group versus 80.3% (73.31-87.25) of patients

130 phopenia occurred in 19 (6%) patients in the fingolimod group versus none in the placebo group, brady

131 le group were matched to 148 patients in the fingolimod group.

132 Over 24 months, in continuous fingolimod groups compared with the group that switched

133 Fingolimod has been approved recently by the US Food and

134 In addition, fingolimod has recently been introduced as the first ora

135 Fingolimod has shown reductions in clinical and MRI dise

136 Oral active drugs such as fingolimod have been weighed down by safety concerns.

137 nd efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort

138 se on IFNbeta-1a were re-randomised (1:1) to fingolimod (IFN-switch; IFN: 0.5/1.25 mg).

139 ificance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, wheth

140 the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns.

141 se of the study was to examine the effect of fingolimod in a mouse model of intracerebral hemorrhage.

142 ata suggest a potential therapeutic role for fingolimod in AD.

143 ese findings suggest that S1PR modulation by fingolimod in both the immune system and CNS, producing

144 Neuroprotective effects of fingolimod in mouse models of Parkinson's disease.

145 We assessed the safety and efficacy of fingolimod in patients with primary progressive multiple

146 enerally consistent with those of studies of fingolimod in patients with relapse-onset multiple scler

147 alizumab is more effective than switching to fingolimod in reducing relapse rate and short-term disab

148 therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral is

149 and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natal

150 further assessed the efficacy and safety of fingolimod in such patients.

151 gned to receive 0.5 mg or 1.25 mg daily oral fingolimod in the core study continued with the same tre

152 A neuroprotective effect of fingolimod in vivo may result from its inhibitory action

153 ntial of the immunosuppressive agent FTY720 (fingolimod) in hepatocellular carcinoma (HCC).

154 re phase continued the same dose (continuous-fingolimod) in the extension, whereas those on IFNbeta-1

155 In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-in

156 FTY720/fingolimod increases NPC1 and NPC2 expression and reduce

157 activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can als

158 ibitors of both pathways, demonstrating that fingolimod-induced cardioprotection was mediated by repe

159 with the mononuclear cell-sequestering drug fingolimod influenced anti-CNS T cell responses in the C

160 reactivation during the WP or shortly after fingolimod initiation.

161 Patients had received fingolimod, interferon beta, or glatiramer acetate for a

162 witching from injectable immunomodulators to fingolimod is associated with fewer relapses, more favor

163 Although S1P1 agonist fingolimod is currently used for the treatment of multip

164 FTY720 (also called fingolimod) is recognized as an immunosuppressant and ha

165 Treatment with fingolimod led to a highly significant reduction in the

166 Switching from interferon beta-1a to fingolimod led to enhanced efficacy with no unexpected s

167 After switching to fingolimod (M0-12 vs M13-EOS), patients initially treate

168 m alone reduced pathological features as did fingolimod (maximally lymphopenic throughout), despite f

169 s, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflamma

170 the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nerv

171 ith multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema.

172 tulated that anti-inflammatory mechanisms of fingolimod might also be protective in Alzheimer's disea

173 Importantly, fingolimod mitigated the development of adverse post-MI

174 ious 12 months (interferon beta-1a to 0.5 mg fingolimod [n=167], 0.31 [95% CI 0.22-0.43] in months 0-

175 13-24 p=0.049; interferon beta-1a to 1.25 mg fingolimod [n=174], 0.29 [0.20-0.40] vs 0.18 [0.12-0.27]

176 vs 0.11 [0.08-0.16] in months 13-24; 1.25 mg fingolimod [n=330], 0.15 [0.10-0.21] vs 0.11 [0.08-0.16]

177 od showed persistent benefits in ARR (0.5 mg fingolimod [n=356], 0.12 [95% CI 0.08-0.17] in months 0-

178 patients were matched (natalizumab, n = 407; fingolimod, n = 171).

179 After switching to fingolimod, numbers of new or newly enlarging T2 and gad

180 were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (

181 of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (

182 rodegeneration, and addressed the effects of fingolimod on astrocyte-neuron interaction and NO synthe

183 We saw no effect of fingolimod on disability progression.

184 MRS also showed an effect of fingolimod on glutamate levels.

185 g-remitting MS who were switching therapy to fingolimod or injectable immunomodulators up to 12 month

186 ls whereas this was not readily observed for fingolimod or monomethylfumarate.

187 th computer-generated blocks to receive oral fingolimod or placebo for at least 36 months and a maxim

188 Animals randomly received fingolimod or saline (control).

189 ophosphatidic acid but not by phosphate-free fingolimod or sphingosine or by phosphate-masked phospha

190 Fingolimod (or saline) was given 30 min after surgery an

191 udy therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Ex

192 monitored their frequencies in untreated and fingolimod- or natalizumab-treated patients with MS.

193 r the switch to natalizumab in comparison to fingolimod (p < 0.001).

194 golimod also readily penetrates the CNS, and fingolimod-P formed in situ may have direct effects on n

195 Its active form, fingolimod-phosphate (fingolimod-P), is a sphingosine 1-phosphate receptor (S1

196 oncentrations of the monoacyl monophosphates fingolimod phosphate, sphingosine 1-phosphate, and lysop

197 Its active form, fingolimod-phosphate (fingolimod-P), is a sphingosine 1-

198 Fingolimod potently inhibits the MS animal model, experi

199 Fingolimod prevents T-cell migration to inflammatory sit

200 cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishm

201 These cases provide evidence for a fingolimod rebound syndrome at a clinically relevant fre

202 e sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for

203 In a transient mouse model, fingolimod reduced infarct size, neurological deficit, e

204 In the clinical trials that led to approval, fingolimod reduced not only acute relapses and magnetic

205 tration of the immunosuppressant drug FTY720/fingolimod reduced ORMDL3 expression and ceramide levels

206 Compound 1 (FTY720, Fingolimod) represents a new generation of immunosuppres

207 ccomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-indu

208 Fingolimod's mechanism of action in MS is not known with

209 Fingolimod's unique mechanism of action distinguishes it

210 Although S1P and phospho-fingolimod share the same structural elements of a zwitt

211 tting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and

212 Patients receiving continuous fingolimod showed persistent benefits in ARR (0.5 mg fin

213 Fingolimod significantly decreased edema, apoptosis and

214 In long-term experiments, fingolimod significantly improved myocardial salvage, re

215 different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenbu

216 ch of the newly approved agents-natalizumab, fingolimod, teriflunomide, dimethyl fumarate, and alemtu

217 ificant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05).

218 atient's VZV immune status before initiating fingolimod therapy and immunization for patients suscept

219 An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examination

220 nd regular follow-up eye examinations during fingolimod therapy are recommended.

221 1P1-deficient mice as well as MS patients on fingolimod therapy had an activated phenotype and were m

222 ults support a continued effect of long-term fingolimod therapy in maintaining a low rate of disease

223 tients relapsed during the first 6 months of fingolimod therapy.

224 Finally, therapeutic administration of fingolimod to EAE mice hampered astrocyte activation and

225 is (EAE) spinal cord, and the spinal cord of fingolimod-treated EAE mice.

226 ssed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg:

227 as accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils,

228 Fingolimod-treated mice showed a smaller infarct and per

229 ely 50% in the first year after switching to fingolimod treatment (44.3% to 66.0%).

230 in the combined T2 lesion area after 6 mo of fingolimod treatment (P = 0.040) but not in the areas of

231 In short-term experiments, fingolimod treatment activated the cardioprotective repe

232 High-dose fingolimod treatment administered before disease onset r

233 Fingolimod treatment also induced EAE in a disease-resis

234 the present investigation of the efficacy of fingolimod treatment for established disease, single-dos

235 Specifically, fingolimod treatment led to a significant reduction in L

236 highlight that rebound events after ceasing fingolimod treatment may happen even with short washout

237 hermore, these data provide insight into how fingolimod treatment might exacerbate CNS neuroinflammat

238 al PET can be used to evaluate the effect of fingolimod treatment on microglial activation.

239 Fingolimod treatment reduced microglial/macrophage activ

240 of severe disease reactivation after ceasing fingolimod treatment using search terms fingolimod and e

241 Of the 46 patients that stopped fingolimod treatment within the 2-year period, 5 (10.9%)

242 w severe neurological symptoms after ceasing fingolimod treatment, with the development of multiple n

243 rformed at baseline and after 8 and 24 wk of fingolimod treatment.

244 tified who experienced rebound after ceasing fingolimod treatment.

245 d severe relapse 4 to 16 weeks after ceasing fingolimod treatment.

246 Occurrence of rebound after ceasing fingolimod treatment.

247 ns of S1P1 and potential impact of long term fingolimod use on Th17 and Treg cell biology and general

248 FTY720/fingolimod, used for treatment of multiple sclerosis, is

249 golimod vs switch group; p=0.002 for 1.25 mg fingolimod vs switch group).

250 Gd-enhancing T1 lesions (p=0.001 for 0.5 mg fingolimod vs switch group; p=0.002 for 1.25 mg fingolim

251 ated using both in vivo and ex vivo imaging (fingolimod vs. vehicle treatment, P < 0.0001).

252 mean washout period before the initiation of fingolimod was 2.3 +/- 1.1 mo.

253 Oral fingolimod was approved in September 2010 by the US Food

254 Fingolimod was associated with a high risk of treatment

255 In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation

256 While the phosphorylated metabolite of fingolimod was found to be a nonselective S1P receptor a

257 In clinical trials, fingolimod was generally safe and well tolerated.

258 tients for whom a switch from natalizumab to fingolimod was planned.

259 oup that switched from interferon beta-1a to fingolimod, we recorded lower ARRs (0.18 [95% CI 0.14-0.

260 Alemtuzumab, natalizumab, and fingolimod were associated with the greatest benefit wit

261 ther adverse events among patients receiving fingolimod were nonfatal herpesvirus infections, bradyca

262 1P) receptor inhibitor FTY720 (also known as Fingolimod), which induces lymphopenia and prevents neur

263 s trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcome

264 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in r