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Your search keyword '"Radue, E. W."' showing total 10 results
Start Over Author "Radue, E. W." Publication Type Electronic Resources
10 results on '"Radue, E. W."'

1. Switching from natalizumab to fingolimod A randomized, placebo-controlled study in RRMS

Author

Kappos, L, Radue, E-W, Comi, G, Montalban, X, Butzkueven, H, Wiendl, H, Giovannoni, G, Hartung, H-P, Derfuss, T, Naegelin, Y, Sprenger, T, Mueller-Lenke, N, Griffiths, S, von Rosenstiel, P, Gottschalk, R, Zhang, Y, Dahlke, F, Tomic, D, Kappos, L, Radue, E-W, Comi, G, Montalban, X, Butzkueven, H, Wiendl, H, Giovannoni, G, Hartung, H-P, Derfuss, T, Naegelin, Y, Sprenger, T, Mueller-Lenke, N, Griffiths, S, von Rosenstiel, P, Gottschalk, R, Zhang, Y, Dahlke, F, and Tomic, D

Abstract

OBJECTIVE: To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in patients switching from natalizumab to fingolimod. METHODS: In this multicenter, double-blind, placebo-controlled trial (TOFINGO), patients with relapsing-remitting multiple sclerosis (RRMS) were randomized 1:1:1 to 8-, 12-, or 16-week WO followed by fingolimod treatment over 32 weeks from last natalizumab infusion (LNI). Brain MRI was performed at baseline and weeks 8, 12, 16, 20, and 24. RESULTS: Of 142 enrolled and randomized patients, 112 (78.9%) completed the study (8 weeks, n = 41/50; 12 weeks, n = 31/42; 16 weeks, n = 40/50). Number (95% confidence interval [CI]) of active (new/newly enlarged T2) lesions from LNI through 8 weeks of fingolimod treatment (primary outcome) was similar in the 8-week (2.1 [1.7-2.6]) and 12-week WO groups (1.7 [1.3-2.2]) and higher in the 16-week WO group (8.2 [7.3-9.1]). During the WO period only, the number (95% CI) of active lesions increased with increasing WO duration (8 weeks, 0.4 [0.2-0.6]; 12 weeks, 2.1 [1.6-2.6]; 16 weeks, 3.6 [3.0-4.2]). Over the 24 weeks from LNI, gadolinium-enhancing T1 lesion counts were lower in the 8-week WO group (14.1 [5.67-22.53]) than in the 12-week (21.3 [1.41-41.19]) or 16-week (18.5 [8.40-28.60]) WO groups. More patients were relapse-free in the 8-week (88%) and 12-week (91%) WO groups than the 16-week WO group (84%). Sixty-eight percent of patients experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or opportunistic infections occurred. CONCLUSIONS: Initiating fingolimod therapy 8-12 weeks after natalizumab discontinuation is associated with a lower risk of MRI and clinical disease reactivation than initiation after 16-week WO. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS switching from natalizumab to fingolimod, shorter natalizumab WO periods a

Published
2015

2. Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy

Author

Metz, I, Radue, E W, Oterino, A, Kümpfel, T, Wiendl, H, Schippling, S, Kuhle, J, Sahraian, M A, Gray, F, Jakl, V, Häusler, D, Brück, W, Metz, I, Radue, E W, Oterino, A, Kümpfel, T, Wiendl, H, Schippling, S, Kuhle, J, Sahraian, M A, Gray, F, Jakl, V, Häusler, D, and Brück, W

Abstract

Natalizumab is an approved medication for highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of this drug. Here, we describe pathological and radiological characteristics of immune reconstitution inflammatory syndrome (IRIS), which occurs in natalizumab-associated PML after the cessation of therapy, and we differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS patients with natalizumab-associated PML were analyzed and their histology compared with non-MS PML. Histology showed an extensive CD8-dominated T cell infiltrate and numerous macrophages within lesions, and in nondemyelinated white and grey matter, in four out of five cases. Few or no virally infected cells were found. This was indicative of IRIS as known from HIV patients with PML. Outstandingly high numbers of plasma cells were present as compared to non-MS PML and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions with a band-like or speckled contrast enhancement either at the lesion edge or within lesions. Only the fifth patient showed typical PML pathology, with low inflammation and high numbers of virally infected cells. This patient showed a similar interval between drug withdrawal and biopsy (3.5 months) to the rest of the cohort (range 2.5-4 months). MRI could not differentiate between PML-associated IRIS and ongoing PML. We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML-IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML.

Published
2012

3. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

Author

Giroux M.-F., Prakash K.G., Serracino-Inglott F., Subramanian G., Symth J.V., Walker M.G., Clarke M., Davis M., Dixit S.A., Dorman P., Dyker A., Ford G., Golkar A., Jackson R., Jayakrishnan V., Lambert D., Lees T., Louw S., Mendelow A.D., Rodgers H., Rose J., Stansby G., Wyatt M., Baker T., Baldwin N., Jones L., Mitchell D., Munro E., Thornton M., Baker D., Davis N., Hamilton G., Platts A., Tibballs J., Beard J., Cleveland T., Dodd D., Gaines P., Lonsdale R., Nair R., Nassef A., Nawaz S., Venables G., Belli A., Clifton A., Cloud G., Halliday A., Markus H., McFarland R., Morgan R., Pereira A., Thompson A., Chataway J., Cheshire N., Gibbs R., Hammady M., Jenkins M., Malik I., Wolfe J., Adiseshiah M., Bishop C., Brew S., Brookes J., Jager R., Kitchen N., Ashleigh R., Butterfield S., Gamble G.E., Nasim A., O'Neill P., Wong J., Edwards R.D., Lees K.R., MacKay A.J., Moss J., Rogers P., Ederle J., Dobson J., Featherstone R.L., Bonati L.H., van der Worp H.B., de Borst G.J., Hauw Lo T., Dorman P.J., Macdonald S., Lyrer P.A., McCollum C., Nederkoorn P.J., Brown M.M., Algra A., Bamford J., Bland M., Hacke W., Mas J.L., McGuire A.J., Sidhu P., Bradbury A., Collins R., Molyneux A., Naylor R., Warlow C., Ferro M., Thomas D., Featherstone R.F., Tindall H., McCabe D., Wallis A., Coward L., Brooks M., Chambers B., Chan A., Chu P., Clark D., Dewey H., Donnan G., Fell G., Hoare M., Molan M., Roberts A., Roberts N., Beiles B., Bladin C., Clifford C., Grigg M., New G., Bell R., Bower S., Chong W., Holt M., Saunder A., Than P.G., Gett S., Leggett D., McGahan T., Quinn J., Ray M., Wong A., Woodruff P., Foreman R., Schultz D., Scroop R., Stanley B., Allard B., Atkinson N., Cambell W., Davies S., Field P., Milne P., Mitchell P., Tress B., Yan B., Beasley A., Dunbabin D., Stary D., Walker S., Cras P., d'Archambeau O., Hendriks J.M.H., Van Schil P., Bosiers M., Deloose K., van Buggenhout E., De Letter J., Devos V., Ghekiere J., Vanhooren G., Astarci P., Hammer F., Lacroix V., Verhelst R., DeJaegher L., Peeters A., Verbist J., Blair J.-F., Caron J.L., Daneault N., Guilbert F., Lanthier S., Lebrun L.-H., Oliva V., Raymond J., Roy D., Soulez G., Weill A., Hill M., Hu W., Hudion M., Morrish W., Sutherland G., Alback A., Harno H., Ijas P., Kaste M., Lepantalo M., Mustanoja S., Paananen T., Porras M., Putaala J., Railo M., Sairanen T., Soinne L., Vehmas A., Vikatmaa P., Goertler M., Halloul Z., Skalej M., Brennan P., Kelly C., Leahy A., Moroney J., Thornton J., Koelemay M.J.W., Reekers J.A.A., Roos Y.B.W.E.M., Hendriks J.M., Koudstaal P.J., Pattynama P.M.T., van der Lugt A., van Dijk L.C., van Sambeek M.R.H.M., van Urk H., Verhagen H.J.M., Bruijninckx C.M.A., de Bruijn S.F., Keunen R., Knippenberg B., Mosch A., Treurniet F., van Dijk L., van Overhagen H., Wever J., de Beer F.C., van den Berg J.S.P., van Hasselt B.A.A.M., Zeilstra D.J., Boiten J., de Mol van Otterloo J.C.A., de Vries A.C., Lycklama a Nijeholt G.J., van der Kallen B.F.W., Blankensteijn J.D., De Leeuw F.E., Schultze Kool L.J., van der Vliet J.A., de Kort G.A.P., Kapelle L.J., Lo T.H., Mali W.P.T.M., Moll F., Verhagen H., Barber P.A., Bourchier R., Hill A., Holden A., Stewart J., Bakke S.J., Krohg-Sorensen K., Skjelland M., Tennoe B., Bialek P., Biejat Z., Czepiel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Lelek M., Polanski J., Kirbis J., Milosevic Z., Zvan B., Blasco J., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Branera J., Canovas D., Estela J., Gimenez Gaibar A., Perendreu J., Bjorses K., Gottsater A., Ivancev K., Maetzsch T., Sonesson B., Berg B., Delle M., Formgren J., Gillgren P., Kall T.-B., Konrad P., Nyman N., Takolander R., Andersson T., Malmstedt J., Soderman M., Wahlgren C., Wahlgren N., Binaghi S., Hirt L., Michel P., Ruchat P., Engelter S.T., Fluri F., Guerke L., Jacob A.L., Kirsch E., Radue E.-W., Stierli P., Wasner M., Wetzel S., Bonvin C., Kalangos A., Lovblad K., Murith N., Ruefenacht D., Sztajzel R., Higgins N., Kirkpatrick P.J., Martin P., Adam D., Bell J., Bradbury A.W., Crowe P., Gannon M., Henderson M.J., Sandler D., Shinton R.A., Scriven J.M., Wilmink T., D'Souza S., Egun A., Guta R., Punekar S., Seriki D.M., Thomson G., Brennan J.A., Enevoldson T.P., Gilling-Smith G., Gould D.A., Harris P.L., McWilliams R.G., Nasser H.-C., White R., Giroux M.-F., Prakash K.G., Serracino-Inglott F., Subramanian G., Symth J.V., Walker M.G., Clarke M., Davis M., Dixit S.A., Dorman P., Dyker A., Ford G., Golkar A., Jackson R., Jayakrishnan V., Lambert D., Lees T., Louw S., Mendelow A.D., Rodgers H., Rose J., Stansby G., Wyatt M., Baker T., Baldwin N., Jones L., Mitchell D., Munro E., Thornton M., Baker D., Davis N., Hamilton G., Platts A., Tibballs J., Beard J., Cleveland T., Dodd D., Gaines P., Lonsdale R., Nair R., Nassef A., Nawaz S., Venables G., Belli A., Clifton A., Cloud G., Halliday A., Markus H., McFarland R., Morgan R., Pereira A., Thompson A., Chataway J., Cheshire N., Gibbs R., Hammady M., Jenkins M., Malik I., Wolfe J., Adiseshiah M., Bishop C., Brew S., Brookes J., Jager R., Kitchen N., Ashleigh R., Butterfield S., Gamble G.E., Nasim A., O'Neill P., Wong J., Edwards R.D., Lees K.R., MacKay A.J., Moss J., Rogers P., Ederle J., Dobson J., Featherstone R.L., Bonati L.H., van der Worp H.B., de Borst G.J., Hauw Lo T., Dorman P.J., Macdonald S., Lyrer P.A., McCollum C., Nederkoorn P.J., Brown M.M., Algra A., Bamford J., Bland M., Hacke W., Mas J.L., McGuire A.J., Sidhu P., Bradbury A., Collins R., Molyneux A., Naylor R., Warlow C., Ferro M., Thomas D., Featherstone R.F., Tindall H., McCabe D., Wallis A., Coward L., Brooks M., Chambers B., Chan A., Chu P., Clark D., Dewey H., Donnan G., Fell G., Hoare M., Molan M., Roberts A., Roberts N., Beiles B., Bladin C., Clifford C., Grigg M., New G., Bell R., Bower S., Chong W., Holt M., Saunder A., Than P.G., Gett S., Leggett D., McGahan T., Quinn J., Ray M., Wong A., Woodruff P., Foreman R., Schultz D., Scroop R., Stanley B., Allard B., Atkinson N., Cambell W., Davies S., Field P., Milne P., Mitchell P., Tress B., Yan B., Beasley A., Dunbabin D., Stary D., Walker S., Cras P., d'Archambeau O., Hendriks J.M.H., Van Schil P., Bosiers M., Deloose K., van Buggenhout E., De Letter J., Devos V., Ghekiere J., Vanhooren G., Astarci P., Hammer F., Lacroix V., Verhelst R., DeJaegher L., Peeters A., Verbist J., Blair J.-F., Caron J.L., Daneault N., Guilbert F., Lanthier S., Lebrun L.-H., Oliva V., Raymond J., Roy D., Soulez G., Weill A., Hill M., Hu W., Hudion M., Morrish W., Sutherland G., Alback A., Harno H., Ijas P., Kaste M., Lepantalo M., Mustanoja S., Paananen T., Porras M., Putaala J., Railo M., Sairanen T., Soinne L., Vehmas A., Vikatmaa P., Goertler M., Halloul Z., Skalej M., Brennan P., Kelly C., Leahy A., Moroney J., Thornton J., Koelemay M.J.W., Reekers J.A.A., Roos Y.B.W.E.M., Hendriks J.M., Koudstaal P.J., Pattynama P.M.T., van der Lugt A., van Dijk L.C., van Sambeek M.R.H.M., van Urk H., Verhagen H.J.M., Bruijninckx C.M.A., de Bruijn S.F., Keunen R., Knippenberg B., Mosch A., Treurniet F., van Dijk L., van Overhagen H., Wever J., de Beer F.C., van den Berg J.S.P., van Hasselt B.A.A.M., Zeilstra D.J., Boiten J., de Mol van Otterloo J.C.A., de Vries A.C., Lycklama a Nijeholt G.J., van der Kallen B.F.W., Blankensteijn J.D., De Leeuw F.E., Schultze Kool L.J., van der Vliet J.A., de Kort G.A.P., Kapelle L.J., Lo T.H., Mali W.P.T.M., Moll F., Verhagen H., Barber P.A., Bourchier R., Hill A., Holden A., Stewart J., Bakke S.J., Krohg-Sorensen K., Skjelland M., Tennoe B., Bialek P., Biejat Z., Czepiel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Lelek M., Polanski J., Kirbis J., Milosevic Z., Zvan B., Blasco J., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Branera J., Canovas D., Estela J., Gimenez Gaibar A., Perendreu J., Bjorses K., Gottsater A., Ivancev K., Maetzsch T., Sonesson B., Berg B., Delle M., Formgren J., Gillgren P., Kall T.-B., Konrad P., Nyman N., Takolander R., Andersson T., Malmstedt J., Soderman M., Wahlgren C., Wahlgren N., Binaghi S., Hirt L., Michel P., Ruchat P., Engelter S.T., Fluri F., Guerke L., Jacob A.L., Kirsch E., Radue E.-W., Stierli P., Wasner M., Wetzel S., Bonvin C., Kalangos A., Lovblad K., Murith N., Ruefenacht D., Sztajzel R., Higgins N., Kirkpatrick P.J., Martin P., Adam D., Bell J., Bradbury A.W., Crowe P., Gannon M., Henderson M.J., Sandler D., Shinton R.A., Scriven J.M., Wilmink T., D'Souza S., Egun A., Guta R., Punekar S., Seriki D.M., Thomson G., Brennan J.A., Enevoldson T.P., Gilling-Smith G., Gould D.A., Harris P.L., McWilliams R.G., Nasser H.-C., and White R.

Abstract

Background: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Method(s): The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Finding(s): The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.

Published
2010

4. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial

Author

Ederle, Jörg, Dobson, Joanna, Featherstone, Roland L., Bonati, Leo H., van der Worp, H. Bart, de Borst, Gert J., Hauw Lo, T., Gaines, Peter, Dorman, Paul J., Macdonald, Sumaira, Lyrer, Philippe A., Hendriks, Johanna M., McCollum, Charles, Nederkoorn, Paul J., Brown, Martin M., Algra, A., Bamford, J., Bland, M., Hacke, W., Mas, J.L., McGuire, A.J., Sidhu, P., Bradbury, A., Collins, R., Molyneux, A., Naylor, R., Warlow, C., Ferro, M., Thomas, D., Featherstone, R.F., Tindall, H., McCabe, D.J.H., Wallis, A., Coward, L., Brooks, M., Chambers, B., Chan, A., Chu, P., Clark, D., Dewey, H., Donnan, G., Fell, G., Hoare, M., Molan, M., Roberts, A., Roberts, N., Beiles, B., Bladin, C., Clifford, C., Grigg, M., New, G., Bell, R., Bower, S., Chong, W., Holt, M., Saunder, A., Than, P.G., Gett, S., Leggett, D., McGahan, T., Quinn, J., Ray, M., Wong, A., Woodruff, P., Foreman, R., Schultz, D., Scroop, R., Stanley, B., Allard, B., Atkinson, N., Cambell, W., Davies, S., Field, P., Milne, P., Mitchell, P., Tress, B., Yan, B., Beasley, A., Dunbabin, D., Stary, D., Walker, S., Cras, P., d'Archambeau, O., Hendriks, J.M.H., Van Schil, P., Bosiers, M., Deloose, K., van Buggenhout, E., De Letter, J., Devos, V., Ghekiere, J., Vanhooren, G., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., DeJaegher, L., Verbist, J., Blair, J.-F., Caron, J.L., Daneault, N., Giroux, M.-F., Guilbert, F., Lanthier, S., Lebrun, L.-H., Oliva, V., Raymond, J., Roy, D., Soulez, G., Weill, A., Hill, M., Hu, W., Hudion, M., Morrish, W., Sutherland, G., Wong, J., Albäck, A., Harno, H., Ijäs, P., Kaste, M., Lepäntalo, M., Mustanoja, S., Paananen, T., Porras, M., Putaala, J., Railo, M., Sairanen, T., Soinne, L., Vehmas, A., Vikatmaa, P., Goertler, M., Halloul, Z., Skalej, M., Brennan, P., Kelly, C., Leahy, A., Moroney, J., Thornton, J., Koelemay, M.J.W., Reekers, J.A.A., Roos, Y.B.W.E.M., Hendriks, J.M., Koudstaal, P.J., Pattynama, P.M.T., van der Lugt, A., van Dijk, L.C., van Sambeek, M.R.H.M., van Urk, H., Verhagen, H.J.M., Bruijninckx, C.M.A., de Bruijn, S.F., Keunen, R., Knippenberg, B., Mosch, A., Treurniet, F., van Dijk, L., van Overhagen, H., Wever, J., de Beer, F.C., van den Berg, J.S.P., van Hasselt, B.A.A.M., Zeilstra, D.J., Boiten, J., de Mol van Otterloo, J.C.A., de Vries, A.C., Lycklama a Nijeholt, G.J., van der Kallen, B.F.W., Blankensteijn, J.D., De Leeuw, F.E., Schultze Kool, L.J., van der Vliet, J.A., de Kort, G.A.P., Kapelle, L.J., Lo, T.H., Mali, W.P.T.M., Moll, F., Verhagen, H., Barber, P.A., Bourchier, R., Hill, A., Holden, A., Stewart, J., Bakke, S.J., Krohg-Sørensen, K., Skjelland, M., Tennøe, B., Bialek, P., Biejat, Z., Czepiel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Lelek, M., Polanski, J., Kirbis, J., Milosevic, Z., Zvan, B., Blasco, J., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Branera, J., Canovas, D., Estela, Jordi, Gimenez Gaibar, A., Perendreu, J., Björses, K., Gottsater, A., Ivancev, K., Maetzsch, T., Sonesson, B., Berg, B., Delle, M., Formgren, J., Gillgren, P., Kall, T.-B., Konrad, P., Nyman, N., Takolander, R., Andersson, T., Malmstedt, J., Soderman, M., Wahlgren, C., Wahlgren, N., Binaghi, S., Hirt, L., Michel, P., Ruchat, P., Engelter, S.T., Fluri, F., Guerke, L., Jacob, A.L., Kirsch, E., Radue, E.-W., Stierli, P., Wasner, M., Wetzel, S., Bonvin, C., Kalangos, A., Lovblad, K., Murith, N., Ruefenacht, D., Sztajzel, R., Higgins, N., Kirkpatrick, P.J., Martin, P., Adam, D., Bell, J., Bradbury, A.W., Crowe, P., Gannon, M., Henderson, M.J., Sandler, D., Shinton, R.A., Scriven, J.M., Wilmink, T., D'Souza, S., Egun, A., Guta, R., Punekar, S., Seriki, D.M., Thomson, G., Brennan, J.A., Enevoldson, T.P., Gilling-Smith, G., Gould, D.A., Harris, P.L., McWilliams, R.G., Nasser, H.-C., White, R., Prakash, K.G., Serracino-Inglott, F., Subramanian, G., Symth, J.V., Walker, M.G., Clarke, M., Davis, M., Dixit, S.A., Dorman, P., Dyker, A., Ford, G., Golkar, A., Jackson, R., Jayakrishnan, V., Lambert, D., Lees, T., Louw, S., Mendelow, A.D., Rodgers, H., Rose, J., Stansby, G., Wyatt, M., Baker, T., Baldwin, N., Jones, L., Mitchell, D., Munro, E., Thornton, M., Baker, D., Davis, N., Hamilton, G., McCabe, D., Platts, A., Tibballs, J., Beard, J., Cleveland, T., Dodd, D., Gaines, P., Lonsdale, R., Nair, R., Nassef, A., Nawaz, S., Venables, G., Belli, A., Clifton, A., Cloud, G., Halliday, A., Markus, H., McFarland, R., Morgan, R., Pereira, A., Thompson, A., Chataway, J., Cheshire, N., Gibbs, R., Hammady, M., Jenkins, M., Malik, I., Wolfe, J., Adiseshiah, M., Bishop, C., Brew, S., Brookes, J., Jäger, R., Kitchen, N., Ashleigh, R., Butterfield, S., Gamble, G.E., Nasim, A., O'Neill, P., Edwards, R.D., Lees, K.R., MacKay, A.J., Moss, J., Rogers, P., Ederle, Jörg, Dobson, Joanna, Featherstone, Roland L., Bonati, Leo H., van der Worp, H. Bart, de Borst, Gert J., Hauw Lo, T., Gaines, Peter, Dorman, Paul J., Macdonald, Sumaira, Lyrer, Philippe A., Hendriks, Johanna M., McCollum, Charles, Nederkoorn, Paul J., Brown, Martin M., Algra, A., Bamford, J., Bland, M., Hacke, W., Mas, J.L., McGuire, A.J., Sidhu, P., Bradbury, A., Collins, R., Molyneux, A., Naylor, R., Warlow, C., Ferro, M., Thomas, D., Featherstone, R.F., Tindall, H., McCabe, D.J.H., Wallis, A., Coward, L., Brooks, M., Chambers, B., Chan, A., Chu, P., Clark, D., Dewey, H., Donnan, G., Fell, G., Hoare, M., Molan, M., Roberts, A., Roberts, N., Beiles, B., Bladin, C., Clifford, C., Grigg, M., New, G., Bell, R., Bower, S., Chong, W., Holt, M., Saunder, A., Than, P.G., Gett, S., Leggett, D., McGahan, T., Quinn, J., Ray, M., Wong, A., Woodruff, P., Foreman, R., Schultz, D., Scroop, R., Stanley, B., Allard, B., Atkinson, N., Cambell, W., Davies, S., Field, P., Milne, P., Mitchell, P., Tress, B., Yan, B., Beasley, A., Dunbabin, D., Stary, D., Walker, S., Cras, P., d'Archambeau, O., Hendriks, J.M.H., Van Schil, P., Bosiers, M., Deloose, K., van Buggenhout, E., De Letter, J., Devos, V., Ghekiere, J., Vanhooren, G., Astarci, P., Hammer, F., Lacroix, V., Peeters, A., Verhelst, R., DeJaegher, L., Verbist, J., Blair, J.-F., Caron, J.L., Daneault, N., Giroux, M.-F., Guilbert, F., Lanthier, S., Lebrun, L.-H., Oliva, V., Raymond, J., Roy, D., Soulez, G., Weill, A., Hill, M., Hu, W., Hudion, M., Morrish, W., Sutherland, G., Wong, J., Albäck, A., Harno, H., Ijäs, P., Kaste, M., Lepäntalo, M., Mustanoja, S., Paananen, T., Porras, M., Putaala, J., Railo, M., Sairanen, T., Soinne, L., Vehmas, A., Vikatmaa, P., Goertler, M., Halloul, Z., Skalej, M., Brennan, P., Kelly, C., Leahy, A., Moroney, J., Thornton, J., Koelemay, M.J.W., Reekers, J.A.A., Roos, Y.B.W.E.M., Hendriks, J.M., Koudstaal, P.J., Pattynama, P.M.T., van der Lugt, A., van Dijk, L.C., van Sambeek, M.R.H.M., van Urk, H., Verhagen, H.J.M., Bruijninckx, C.M.A., de Bruijn, S.F., Keunen, R., Knippenberg, B., Mosch, A., Treurniet, F., van Dijk, L., van Overhagen, H., Wever, J., de Beer, F.C., van den Berg, J.S.P., van Hasselt, B.A.A.M., Zeilstra, D.J., Boiten, J., de Mol van Otterloo, J.C.A., de Vries, A.C., Lycklama a Nijeholt, G.J., van der Kallen, B.F.W., Blankensteijn, J.D., De Leeuw, F.E., Schultze Kool, L.J., van der Vliet, J.A., de Kort, G.A.P., Kapelle, L.J., Lo, T.H., Mali, W.P.T.M., Moll, F., Verhagen, H., Barber, P.A., Bourchier, R., Hill, A., Holden, A., Stewart, J., Bakke, S.J., Krohg-Sørensen, K., Skjelland, M., Tennøe, B., Bialek, P., Biejat, Z., Czepiel, W., Czlonkowska, A., Dowzenko, A., Jedrzejewska, J., Kobayashi, A., Lelek, M., Polanski, J., Kirbis, J., Milosevic, Z., Zvan, B., Blasco, J., Chamorro, A., Macho, J., Obach, V., Riambau, V., San Roman, L., Branera, J., Canovas, D., Estela, Jordi, Gimenez Gaibar, A., Perendreu, J., Björses, K., Gottsater, A., Ivancev, K., Maetzsch, T., Sonesson, B., Berg, B., Delle, M., Formgren, J., Gillgren, P., Kall, T.-B., Konrad, P., Nyman, N., Takolander, R., Andersson, T., Malmstedt, J., Soderman, M., Wahlgren, C., Wahlgren, N., Binaghi, S., Hirt, L., Michel, P., Ruchat, P., Engelter, S.T., Fluri, F., Guerke, L., Jacob, A.L., Kirsch, E., Radue, E.-W., Stierli, P., Wasner, M., Wetzel, S., Bonvin, C., Kalangos, A., Lovblad, K., Murith, N., Ruefenacht, D., Sztajzel, R., Higgins, N., Kirkpatrick, P.J., Martin, P., Adam, D., Bell, J., Bradbury, A.W., Crowe, P., Gannon, M., Henderson, M.J., Sandler, D., Shinton, R.A., Scriven, J.M., Wilmink, T., D'Souza, S., Egun, A., Guta, R., Punekar, S., Seriki, D.M., Thomson, G., Brennan, J.A., Enevoldson, T.P., Gilling-Smith, G., Gould, D.A., Harris, P.L., McWilliams, R.G., Nasser, H.-C., White, R., Prakash, K.G., Serracino-Inglott, F., Subramanian, G., Symth, J.V., Walker, M.G., Clarke, M., Davis, M., Dixit, S.A., Dorman, P., Dyker, A., Ford, G., Golkar, A., Jackson, R., Jayakrishnan, V., Lambert, D., Lees, T., Louw, S., Mendelow, A.D., Rodgers, H., Rose, J., Stansby, G., Wyatt, M., Baker, T., Baldwin, N., Jones, L., Mitchell, D., Munro, E., Thornton, M., Baker, D., Davis, N., Hamilton, G., McCabe, D., Platts, A., Tibballs, J., Beard, J., Cleveland, T., Dodd, D., Gaines, P., Lonsdale, R., Nair, R., Nassef, A., Nawaz, S., Venables, G., Belli, A., Clifton, A., Cloud, G., Halliday, A., Markus, H., McFarland, R., Morgan, R., Pereira, A., Thompson, A., Chataway, J., Cheshire, N., Gibbs, R., Hammady, M., Jenkins, M., Malik, I., Wolfe, J., Adiseshiah, M., Bishop, C., Brew, S., Brookes, J., Jäger, R., Kitchen, N., Ashleigh, R., Butterfield, S., Gamble, G.E., Nasim, A., O'Neill, P., Edwards, R.D., Lees, K.R., MacKay, A.J., Moss, J., and Rogers, P.

Abstract

Background: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77-2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16-2

Published
2010

5. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial.

Author

Giroux M.-F., Prakash K.G., Serracino-Inglott F., Subramanian G., Symth J.V., Walker M.G., Clarke M., Davis M., Dixit S.A., Dorman P., Dyker A., Ford G., Golkar A., Jackson R., Jayakrishnan V., Lambert D., Lees T., Louw S., Mendelow A.D., Rodgers H., Rose J., Stansby G., Wyatt M., Baker T., Baldwin N., Jones L., Mitchell D., Munro E., Thornton M., Baker D., Davis N., Hamilton G., Platts A., Tibballs J., Beard J., Cleveland T., Dodd D., Gaines P., Lonsdale R., Nair R., Nassef A., Nawaz S., Venables G., Belli A., Clifton A., Cloud G., Halliday A., Markus H., McFarland R., Morgan R., Pereira A., Thompson A., Chataway J., Cheshire N., Gibbs R., Hammady M., Jenkins M., Malik I., Wolfe J., Adiseshiah M., Bishop C., Brew S., Brookes J., Jager R., Kitchen N., Ashleigh R., Butterfield S., Gamble G.E., Nasim A., O'Neill P., Wong J., Edwards R.D., Lees K.R., MacKay A.J., Moss J., Rogers P., Ederle J., Dobson J., Featherstone R.L., Bonati L.H., van der Worp H.B., de Borst G.J., Hauw Lo T., Dorman P.J., Macdonald S., Lyrer P.A., McCollum C., Nederkoorn P.J., Brown M.M., Algra A., Bamford J., Bland M., Hacke W., Mas J.L., McGuire A.J., Sidhu P., Bradbury A., Collins R., Molyneux A., Naylor R., Warlow C., Ferro M., Thomas D., Featherstone R.F., Tindall H., McCabe D., Wallis A., Coward L., Brooks M., Chambers B., Chan A., Chu P., Clark D., Dewey H., Donnan G., Fell G., Hoare M., Molan M., Roberts A., Roberts N., Beiles B., Bladin C., Clifford C., Grigg M., New G., Bell R., Bower S., Chong W., Holt M., Saunder A., Than P.G., Gett S., Leggett D., McGahan T., Quinn J., Ray M., Wong A., Woodruff P., Foreman R., Schultz D., Scroop R., Stanley B., Allard B., Atkinson N., Cambell W., Davies S., Field P., Milne P., Mitchell P., Tress B., Yan B., Beasley A., Dunbabin D., Stary D., Walker S., Cras P., d'Archambeau O., Hendriks J.M.H., Van Schil P., Bosiers M., Deloose K., van Buggenhout E., De Letter J., Devos V., Ghekiere J., Vanhooren G., Astarci P., Hammer F., Lacroix V., Verhelst R., DeJaegher L., Peeters A., Verbist J., Blair J.-F., Caron J.L., Daneault N., Guilbert F., Lanthier S., Lebrun L.-H., Oliva V., Raymond J., Roy D., Soulez G., Weill A., Hill M., Hu W., Hudion M., Morrish W., Sutherland G., Alback A., Harno H., Ijas P., Kaste M., Lepantalo M., Mustanoja S., Paananen T., Porras M., Putaala J., Railo M., Sairanen T., Soinne L., Vehmas A., Vikatmaa P., Goertler M., Halloul Z., Skalej M., Brennan P., Kelly C., Leahy A., Moroney J., Thornton J., Koelemay M.J.W., Reekers J.A.A., Roos Y.B.W.E.M., Hendriks J.M., Koudstaal P.J., Pattynama P.M.T., van der Lugt A., van Dijk L.C., van Sambeek M.R.H.M., van Urk H., Verhagen H.J.M., Bruijninckx C.M.A., de Bruijn S.F., Keunen R., Knippenberg B., Mosch A., Treurniet F., van Dijk L., van Overhagen H., Wever J., de Beer F.C., van den Berg J.S.P., van Hasselt B.A.A.M., Zeilstra D.J., Boiten J., de Mol van Otterloo J.C.A., de Vries A.C., Lycklama a Nijeholt G.J., van der Kallen B.F.W., Blankensteijn J.D., De Leeuw F.E., Schultze Kool L.J., van der Vliet J.A., de Kort G.A.P., Kapelle L.J., Lo T.H., Mali W.P.T.M., Moll F., Verhagen H., Barber P.A., Bourchier R., Hill A., Holden A., Stewart J., Bakke S.J., Krohg-Sorensen K., Skjelland M., Tennoe B., Bialek P., Biejat Z., Czepiel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Lelek M., Polanski J., Kirbis J., Milosevic Z., Zvan B., Blasco J., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Branera J., Canovas D., Estela J., Gimenez Gaibar A., Perendreu J., Bjorses K., Gottsater A., Ivancev K., Maetzsch T., Sonesson B., Berg B., Delle M., Formgren J., Gillgren P., Kall T.-B., Konrad P., Nyman N., Takolander R., Andersson T., Malmstedt J., Soderman M., Wahlgren C., Wahlgren N., Binaghi S., Hirt L., Michel P., Ruchat P., Engelter S.T., Fluri F., Guerke L., Jacob A.L., Kirsch E., Radue E.-W., Stierli P., Wasner M., Wetzel S., Bonvin C., Kalangos A., Lovblad K., Murith N., Ruefenacht D., Sztajzel R., Higgins N., Kirkpatrick P.J., Martin P., Adam D., Bell J., Bradbury A.W., Crowe P., Gannon M., Henderson M.J., Sandler D., Shinton R.A., Scriven J.M., Wilmink T., D'Souza S., Egun A., Guta R., Punekar S., Seriki D.M., Thomson G., Brennan J.A., Enevoldson T.P., Gilling-Smith G., Gould D.A., Harris P.L., McWilliams R.G., Nasser H.-C., White R., Giroux M.-F., Prakash K.G., Serracino-Inglott F., Subramanian G., Symth J.V., Walker M.G., Clarke M., Davis M., Dixit S.A., Dorman P., Dyker A., Ford G., Golkar A., Jackson R., Jayakrishnan V., Lambert D., Lees T., Louw S., Mendelow A.D., Rodgers H., Rose J., Stansby G., Wyatt M., Baker T., Baldwin N., Jones L., Mitchell D., Munro E., Thornton M., Baker D., Davis N., Hamilton G., Platts A., Tibballs J., Beard J., Cleveland T., Dodd D., Gaines P., Lonsdale R., Nair R., Nassef A., Nawaz S., Venables G., Belli A., Clifton A., Cloud G., Halliday A., Markus H., McFarland R., Morgan R., Pereira A., Thompson A., Chataway J., Cheshire N., Gibbs R., Hammady M., Jenkins M., Malik I., Wolfe J., Adiseshiah M., Bishop C., Brew S., Brookes J., Jager R., Kitchen N., Ashleigh R., Butterfield S., Gamble G.E., Nasim A., O'Neill P., Wong J., Edwards R.D., Lees K.R., MacKay A.J., Moss J., Rogers P., Ederle J., Dobson J., Featherstone R.L., Bonati L.H., van der Worp H.B., de Borst G.J., Hauw Lo T., Dorman P.J., Macdonald S., Lyrer P.A., McCollum C., Nederkoorn P.J., Brown M.M., Algra A., Bamford J., Bland M., Hacke W., Mas J.L., McGuire A.J., Sidhu P., Bradbury A., Collins R., Molyneux A., Naylor R., Warlow C., Ferro M., Thomas D., Featherstone R.F., Tindall H., McCabe D., Wallis A., Coward L., Brooks M., Chambers B., Chan A., Chu P., Clark D., Dewey H., Donnan G., Fell G., Hoare M., Molan M., Roberts A., Roberts N., Beiles B., Bladin C., Clifford C., Grigg M., New G., Bell R., Bower S., Chong W., Holt M., Saunder A., Than P.G., Gett S., Leggett D., McGahan T., Quinn J., Ray M., Wong A., Woodruff P., Foreman R., Schultz D., Scroop R., Stanley B., Allard B., Atkinson N., Cambell W., Davies S., Field P., Milne P., Mitchell P., Tress B., Yan B., Beasley A., Dunbabin D., Stary D., Walker S., Cras P., d'Archambeau O., Hendriks J.M.H., Van Schil P., Bosiers M., Deloose K., van Buggenhout E., De Letter J., Devos V., Ghekiere J., Vanhooren G., Astarci P., Hammer F., Lacroix V., Verhelst R., DeJaegher L., Peeters A., Verbist J., Blair J.-F., Caron J.L., Daneault N., Guilbert F., Lanthier S., Lebrun L.-H., Oliva V., Raymond J., Roy D., Soulez G., Weill A., Hill M., Hu W., Hudion M., Morrish W., Sutherland G., Alback A., Harno H., Ijas P., Kaste M., Lepantalo M., Mustanoja S., Paananen T., Porras M., Putaala J., Railo M., Sairanen T., Soinne L., Vehmas A., Vikatmaa P., Goertler M., Halloul Z., Skalej M., Brennan P., Kelly C., Leahy A., Moroney J., Thornton J., Koelemay M.J.W., Reekers J.A.A., Roos Y.B.W.E.M., Hendriks J.M., Koudstaal P.J., Pattynama P.M.T., van der Lugt A., van Dijk L.C., van Sambeek M.R.H.M., van Urk H., Verhagen H.J.M., Bruijninckx C.M.A., de Bruijn S.F., Keunen R., Knippenberg B., Mosch A., Treurniet F., van Dijk L., van Overhagen H., Wever J., de Beer F.C., van den Berg J.S.P., van Hasselt B.A.A.M., Zeilstra D.J., Boiten J., de Mol van Otterloo J.C.A., de Vries A.C., Lycklama a Nijeholt G.J., van der Kallen B.F.W., Blankensteijn J.D., De Leeuw F.E., Schultze Kool L.J., van der Vliet J.A., de Kort G.A.P., Kapelle L.J., Lo T.H., Mali W.P.T.M., Moll F., Verhagen H., Barber P.A., Bourchier R., Hill A., Holden A., Stewart J., Bakke S.J., Krohg-Sorensen K., Skjelland M., Tennoe B., Bialek P., Biejat Z., Czepiel W., Czlonkowska A., Dowzenko A., Jedrzejewska J., Kobayashi A., Lelek M., Polanski J., Kirbis J., Milosevic Z., Zvan B., Blasco J., Chamorro A., Macho J., Obach V., Riambau V., San Roman L., Branera J., Canovas D., Estela J., Gimenez Gaibar A., Perendreu J., Bjorses K., Gottsater A., Ivancev K., Maetzsch T., Sonesson B., Berg B., Delle M., Formgren J., Gillgren P., Kall T.-B., Konrad P., Nyman N., Takolander R., Andersson T., Malmstedt J., Soderman M., Wahlgren C., Wahlgren N., Binaghi S., Hirt L., Michel P., Ruchat P., Engelter S.T., Fluri F., Guerke L., Jacob A.L., Kirsch E., Radue E.-W., Stierli P., Wasner M., Wetzel S., Bonvin C., Kalangos A., Lovblad K., Murith N., Ruefenacht D., Sztajzel R., Higgins N., Kirkpatrick P.J., Martin P., Adam D., Bell J., Bradbury A.W., Crowe P., Gannon M., Henderson M.J., Sandler D., Shinton R.A., Scriven J.M., Wilmink T., D'Souza S., Egun A., Guta R., Punekar S., Seriki D.M., Thomson G., Brennan J.A., Enevoldson T.P., Gilling-Smith G., Gould D.A., Harris P.L., McWilliams R.G., Nasser H.-C., and White R.

Abstract

Background: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Method(s): The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Finding(s): The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.

Published
2010

6. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results

Author

Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, E-W, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Sørensen, Per Soelberg, Frederiksen, Jette Lautrup Battistini, Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, E-W, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Sørensen, Per Soelberg, and Frederiksen, Jette Lautrup Battistini

Abstract

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7-36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15-24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88-89%) or new T2 lesions (70-78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20-0.21, and 68-73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3-5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

Published
2010

7. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results

Author

Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, E-W, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Sørensen, Per Soelberg, Frederiksen, Jette Lautrup Battistini, Comi, G, O'Connor, P, Montalban, X, Antel, J, Radue, E-W, Karlsson, G, Pohlmann, H, Aradhye, S, Kappos, L, Sørensen, Per Soelberg, and Frederiksen, Jette Lautrup Battistini

Abstract

In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7-36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15-24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88-89%) or new T2 lesions (70-78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20-0.21, and 68-73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3-5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

Published
2010

8. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

Author

O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, E W, de Vera, A, Pohlmann, H, Kappos, L, Battistini, Jette Lautrup, O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, E W, de Vera, A, Pohlmann, H, Kappos, L, and Battistini, Jette Lautrup

Abstract

OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd(+)) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd(+) lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity.

Published
2009

9. Oral fingolimod (FTY720) in multiple sclerosis: two-year results of a phase II extension study

Author

O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, E W, de Vera, A, Pohlmann, H, Kappos, L, Battistini, Jette Lautrup, O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, E W, de Vera, A, Pohlmann, H, Kappos, L, and Battistini, Jette Lautrup

Abstract

OBJECTIVE: To report the results of a 24-month extension of a phase II trial assessing the efficacy, safety, and tolerability of the once-daily oral sphingosine-1-phosphate receptor modulator, fingolimod (FTY720), in relapsing multiple sclerosis (MS). METHODS: In the randomized, double-blind, placebo-controlled core study, 281 patients received placebo or FTY720, 1.25 or 5.0 mg/day, for 6 months. During the subsequent dose-blinded extension, patients assigned to placebo were re-randomized to either dose of FTY720; those originally assigned to FTY720 continued at the same dose. Patients receiving FTY720 5.0 mg were switched to 1.25 mg during the month 15 to month 24 study visits. RESULTS: Of 281 patients randomized in the core study, 250 (89%) entered the extension phase, and 189 (75.6%) received treatment for 24 months. During the core study, FTY720 significantly reduced gadolinium-enhanced (Gd(+)) lesions and annualized relapse rate (ARR) compared with placebo, with no differences between doses. During the extension phase, patients who switched from placebo to FTY720 showed clear reductions in ARR and lesion counts compared with the placebo phase; ARR and lesion counts remained low in patients who continued FTY720 treatment. After 24 months, 79 to 91% of patients were free from Gd(+) lesions and up to 77% of patients remained relapse free. FTY720 was well tolerated; no new safety concerns emerged during months 7 to 24 compared with the 6-month core study. CONCLUSIONS: Once-daily oral treatment with FTY720, 1.25 or 5.0 mg, for up to 2 years, was well tolerated and was associated with low relapse rates and lesion activity.

Published
2009

10. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial

Author

Ederle, J, Dobson, J, Featherstone, RL, Bonati, LH, van der Worp, HB, de Borst, GJ, Lo, TH, Gaines, P, Dorman, PJ, Macdonald, S, Lyrer, PA, Hendriks, JM, McCollum, C, Nederkoorn, PJ, Brown, MM, Algra, A, Bamford, J, Beard, J, Bland, M, Bradbury, AW, Clifton, A, Hacke, W, Halliday, A, Malik, I, Mas, JL, McGuire, AJ, Sidhu, P, Venables, G, Bradbury, A, Collins, R, Molynewc, A, Naylor, R, Warlow, C, Ferro, JM, Thomas, D, Coward, L, Featherstone, RF, Tindall, H, McCabe, DJH, Wallis, A, Brooks, M, Chambers, B, Chan, A, Chu, P, Clark, D, Dewey, H, Donnan, G, Fell, G, Hoare, M, Molan, M, Roberts, A, Roberts, N, Beiles, B, Bladin, C, Clifford, C, Grigg, M, New, G, Bell, R, Bower, S, Chong, W, Holt, M, Saunder, A, Than, PG, Gett, S, Leggett, D, McGahan, T, Quinn, J, Ray, M, Wong, A, Woodruff, P, Foreman, R, Schultz, D, Scroop, R, Stanley, B, Allard, B, Atkinson, N, Cambell, W, Davies, S, Field, P, Milne, P, Mitchell, P, Tress, B, Yan, B, Beasley, A, Dunbabin, D, Stary, D, Walker, S, Cras, P, d'Archambeau, O, Hendriks, JMH, Van Schil, P, Bosiers, M, Deloose, K, van Buggenhout, E, De Letter, J, Devos, V, Ghekiere, J, Vanhooren, G, Astarci, P, Hammer, F, Lacroix, V, Peeters, A, Verhelst, R, DeJaegher, L, Verbist, J, Blair, J-F, Caron, JL, Daneault, N, Giroux, M-F, Guilbert, F, Lanthier, S, Lebrun, L-H, Oliva, V, Raymond, J, Roy, D, Soulez, G, Weill, A, Hill, M, Hu, W, Hudion, M, Morrish, W, Sutherland, G, Wong, J, Alback, A, Harno, H, Ijas, P, Kaste, M, Lepantalo, M, Mustanoja, S, Paananen, T, Porras, M, Putaala, J, Railo, M, Sairanen, T, Soinne, L, Vehmas, A, Vikatmaa, P, Goertler, M, Halloul, Z, Skalej, M, Brennan, P, Kelly, C, Leahy, A, Moroney, J, Thornton, J, Koelemay, MJW, Reekers, JAA, Roos, YBWEM, Koudstaal, PJ, Pattynama, PMT, van der Lugt, A, van Dijk, LC, van Sambeek, MRHM, van Urk, H, Verhagen, HJM, Bruininckx, CMA, de Bruijn, SF, Keunen, R, Knippenberg, B, Mosch, A, Treurniet, F, van Dijk, L, van Overhagen, H, Wever, J, de Beer, FC, van den Berg, JSP, van Hasselt, BAAM, Zeilstra, DJ, Boiten, J, van Otterloo, JCADM, de Vries, AC, Nieholt, GJLA, van der Kallen, BFW, Blankensteijn, JD, De Leeuw, FE, Kool, LJS, van der Vliet, JA, de Kort, GAP, Kapelle, LJ, Mali, WPTM, Moll, F, Verhagen, H, Barber, PA, Bourchier, R, Hill, A, Holden, A, Stewart, J, Bakke, SJ, Krohg-Sorensen, K, Skjelland, M, Tennoe, B, Bialek, P, Biejat, Z, Czepiel, W, Czlonkowska, A, Dowzenko, A, Jedrzejewska, J, Kobayashi, A, Lelek, M, Polanski, J, Kirbis, J, Milosevic, Z, Zvan, B, Blasco, J, Chamorro, A, Macho, J, Obach, V, Riambau, V, San Roman, L, Branera, J, Canovas, D, Estela, J, Gimenez Gaibar, A, Perendreu, J, Bjorses, K, Gottsater, A, Ivancev, K, Maetzsch, T, Sonesson, B, Berg, B, Delle, M, Formgren, J, Gillgren, P, Kall, T-B, Konrad, P, Nyman, N, Takolander, R, Andersson, T, Malmstedt, J, Soderman, M, Wahlgren, C, Wahlgren, N, Binaghi, S, Hirt, L, Michel, P, Ruchat, P, Engelter, ST, Fluri, F, Guerke, L, Jacob, AL, Kirsch, E, Radue, E-W, Stierli, P, Wasner, M, Wetzel, S, Bonvin, C, Kalangos, A, Lovblad, K, Murith, N, Ruefenacht, D, Sztajzel, R, Higgins, N, Kirkpatrick, PJ, Martin, P, Adam, D, Bell, J, Crowe, P, Gannon, M, Henderson, MJ, Sandler, D, Shinton, RA, Scriven, JM, Wilmink, T, D'Souza, S, Egun, A, Guta, R, Punekar, S, Seriki, DM, Thomson, G, Brennan, A, Enevoldson, TP, Gilling-Smith, G, Gould, DA, Harris, PL, McWilliams, RG, Nasser, H-C, White, R, Prakash, KG, Serracino-Inglott, F, Subramanian, G, Symth, JV, Walker, MG, Clarke, M, Davis, M, Dixit, SA, Dolman, P, Dyker, A, Ford, G, Golkar, A, Jackson, R, Jayakrishnan, V, Lambert, D, Lees, T, Louw, S, Mendelow, AD, Rodgers, H, Rose, J, Stansby, G, Wyatt, M, Baker, T, Baldwin, N, Jones, L, Mitchell, D, Munro, E, Thornton, M, Baker, D, Davis, N, Hamilton, G, McCabe, D, Platts, A, Tibballs, J, Cleveland, T, Dodd, D, Lonsdale, R, Nair, R, Nassef, A, Nawaz, S, Belli, A, Cloud, G, Markus, H, McFarland, R, Morgan, R, Pereira, A, Thompson, A, Chataway, J, Cheshire, N, Gibbs, R, Hammady, M, Jenkins, M, Wolfe, J, Adiseshiah, M, Bishop, C, Brew, S, Brookes, J, Jaeger, R, Kitchen, N, Ashleigh, R, Butterfield, S, Gamble, GE, Nasim, A, O'Neill, P, Edwards, RD, Lees, KR, MacKay, AJ, Moss, J, Rogers, P, Ederle, J, Dobson, J, Featherstone, RL, Bonati, LH, van der Worp, HB, de Borst, GJ, Lo, TH, Gaines, P, Dorman, PJ, Macdonald, S, Lyrer, PA, Hendriks, JM, McCollum, C, Nederkoorn, PJ, Brown, MM, Algra, A, Bamford, J, Beard, J, Bland, M, Bradbury, AW, Clifton, A, Hacke, W, Halliday, A, Malik, I, Mas, JL, McGuire, AJ, Sidhu, P, Venables, G, Bradbury, A, Collins, R, Molynewc, A, Naylor, R, Warlow, C, Ferro, JM, Thomas, D, Coward, L, Featherstone, RF, Tindall, H, McCabe, DJH, Wallis, A, Brooks, M, Chambers, B, Chan, A, Chu, P, Clark, D, Dewey, H, Donnan, G, Fell, G, Hoare, M, Molan, M, Roberts, A, Roberts, N, Beiles, B, Bladin, C, Clifford, C, Grigg, M, New, G, Bell, R, Bower, S, Chong, W, Holt, M, Saunder, A, Than, PG, Gett, S, Leggett, D, McGahan, T, Quinn, J, Ray, M, Wong, A, Woodruff, P, Foreman, R, Schultz, D, Scroop, R, Stanley, B, Allard, B, Atkinson, N, Cambell, W, Davies, S, Field, P, Milne, P, Mitchell, P, Tress, B, Yan, B, Beasley, A, Dunbabin, D, Stary, D, Walker, S, Cras, P, d'Archambeau, O, Hendriks, JMH, Van Schil, P, Bosiers, M, Deloose, K, van Buggenhout, E, De Letter, J, Devos, V, Ghekiere, J, Vanhooren, G, Astarci, P, Hammer, F, Lacroix, V, Peeters, A, Verhelst, R, DeJaegher, L, Verbist, J, Blair, J-F, Caron, JL, Daneault, N, Giroux, M-F, Guilbert, F, Lanthier, S, Lebrun, L-H, Oliva, V, Raymond, J, Roy, D, Soulez, G, Weill, A, Hill, M, Hu, W, Hudion, M, Morrish, W, Sutherland, G, Wong, J, Alback, A, Harno, H, Ijas, P, Kaste, M, Lepantalo, M, Mustanoja, S, Paananen, T, Porras, M, Putaala, J, Railo, M, Sairanen, T, Soinne, L, Vehmas, A, Vikatmaa, P, Goertler, M, Halloul, Z, Skalej, M, Brennan, P, Kelly, C, Leahy, A, Moroney, J, Thornton, J, Koelemay, MJW, Reekers, JAA, Roos, YBWEM, Koudstaal, PJ, Pattynama, PMT, van der Lugt, A, van Dijk, LC, van Sambeek, MRHM, van Urk, H, Verhagen, HJM, Bruininckx, CMA, de Bruijn, SF, Keunen, R, Knippenberg, B, Mosch, A, Treurniet, F, van Dijk, L, van Overhagen, H, Wever, J, de Beer, FC, van den Berg, JSP, van Hasselt, BAAM, Zeilstra, DJ, Boiten, J, van Otterloo, JCADM, de Vries, AC, Nieholt, GJLA, van der Kallen, BFW, Blankensteijn, JD, De Leeuw, FE, Kool, LJS, van der Vliet, JA, de Kort, GAP, Kapelle, LJ, Mali, WPTM, Moll, F, Verhagen, H, Barber, PA, Bourchier, R, Hill, A, Holden, A, Stewart, J, Bakke, SJ, Krohg-Sorensen, K, Skjelland, M, Tennoe, B, Bialek, P, Biejat, Z, Czepiel, W, Czlonkowska, A, Dowzenko, A, Jedrzejewska, J, Kobayashi, A, Lelek, M, Polanski, J, Kirbis, J, Milosevic, Z, Zvan, B, Blasco, J, Chamorro, A, Macho, J, Obach, V, Riambau, V, San Roman, L, Branera, J, Canovas, D, Estela, J, Gimenez Gaibar, A, Perendreu, J, Bjorses, K, Gottsater, A, Ivancev, K, Maetzsch, T, Sonesson, B, Berg, B, Delle, M, Formgren, J, Gillgren, P, Kall, T-B, Konrad, P, Nyman, N, Takolander, R, Andersson, T, Malmstedt, J, Soderman, M, Wahlgren, C, Wahlgren, N, Binaghi, S, Hirt, L, Michel, P, Ruchat, P, Engelter, ST, Fluri, F, Guerke, L, Jacob, AL, Kirsch, E, Radue, E-W, Stierli, P, Wasner, M, Wetzel, S, Bonvin, C, Kalangos, A, Lovblad, K, Murith, N, Ruefenacht, D, Sztajzel, R, Higgins, N, Kirkpatrick, PJ, Martin, P, Adam, D, Bell, J, Crowe, P, Gannon, M, Henderson, MJ, Sandler, D, Shinton, RA, Scriven, JM, Wilmink, T, D'Souza, S, Egun, A, Guta, R, Punekar, S, Seriki, DM, Thomson, G, Brennan, A, Enevoldson, TP, Gilling-Smith, G, Gould, DA, Harris, PL, McWilliams, RG, Nasser, H-C, White, R, Prakash, KG, Serracino-Inglott, F, Subramanian, G, Symth, JV, Walker, MG, Clarke, M, Davis, M, Dixit, SA, Dolman, P, Dyker, A, Ford, G, Golkar, A, Jackson, R, Jayakrishnan, V, Lambert, D, Lees, T, Louw, S, Mendelow, AD, Rodgers, H, Rose, J, Stansby, G, Wyatt, M, Baker, T, Baldwin, N, Jones, L, Mitchell, D, Munro, E, Thornton, M, Baker, D, Davis, N, Hamilton, G, McCabe, D, Platts, A, Tibballs, J, Cleveland, T, Dodd, D, Lonsdale, R, Nair, R, Nassef, A, Nawaz, S, Belli, A, Cloud, G, Markus, H, McFarland, R, Morgan, R, Pereira, A, Thompson, A, Chataway, J, Cheshire, N, Gibbs, R, Hammady, M, Jenkins, M, Wolfe, J, Adiseshiah, M, Bishop, C, Brew, S, Brookes, J, Jaeger, R, Kitchen, N, Ashleigh, R, Butterfield, S, Gamble, GE, Nasim, A, O'Neill, P, Edwards, RD, Lees, KR, MacKay, AJ, Moss, J, and Rogers, P

Abstract

Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45

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