Objective The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients. Methods These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP. Results As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab’s known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0–11.6) years; median follow-up time was 5.2 (range 0–10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias. Conclusions Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab. Trial registration number NCT00493298 .
Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP)
[저자] Helmut Butzkueven, Ludwig Kappos, Heinz Wiendl, Maria Trojano, Tim Spelman, Ih Chang, Rachna Kasliwal, Seema Jaitly, Nolan Campbell, Pei-Ran Ho, Stephanie Licata,
On behalf of the Tysabri Observational Program (TOP) Investigators
Abraham Roby Adamkova Jana Airas Laura Aktas Orhan Albrecht Holger Alsassa Roger de Arcaya Esquide Amaya Alvarez Angstwurm Klemens Anne Olivier Anvari Kerstin Aram Julia Atula Sari Augspach-Hofmann Regine Barnett Michael Barroso Bruno Barthomolé Emmanuel Nadal Jordi Batlle Bayas Antonios Bergmann Arnfin Berkenfeld Ralf Berthele Achim Bertolotto Antonio Billy Christophe Bitsch Andreas Bohr Kin-Arno Böhringer Johannes Borsotti Jean Paul Bos M. Bouquiaux Olivier Bourteel Hélène Brosch Thomas Buehler Bernhard Bureau Michel Busson Philippe Butzkueven Helmut Caekebeke Jo Hernández Carmen Calles Caminero Rodríguez Ana Belén Caride Alejandro Triviño Tamara Castillo Constantinescu Cris Correale Jorge Costa Guerra José Manuel Crols Roeland D’Haeseleer Miguel de Gans Koen de Jesus Jimeez Maria de la Luz Villalpando Ma Pauw Adinda De Decoo Danny Delalande Sophie Delerue Olivier Delvaux Valérie Dereeper Olivier Deri Norma H. Deryck Olivier Devy Richard D'Hooghe Marie Domke Sylke Dubois Benedicte Duddy Martin Dufek Michal Duhin Emeline Dupuis Michel Eck Philippe Eder Hans-Thomas Edland Astrid Ehrlich Sven Eisenberg Eli Skromne Elias Wolfgang-Gerhard Erdmann Evelyn Ernst Michael Estudillo Rocio Márquez Faiss Juergen Fanjaud Guy Farbu Elisabeth Faucheux Jean Marc Fiedler Jiri Flores Ciro Jesús Alfredo Flores Ramirez Francisco Gerardo de Jesus Flores Rivera Jose Florio Ciro Frank Benedikt Gasperini Claudio Geens Karine Gehring Klaus Ghalamfarsa Sohrab Mostoufizadeh Giraud Pierric Godet Etienne Guardado Antonio Gonzalez Gössling Jens Grand'Maison François Gratz Thomas Gray Orla Grimaldi Luigi Grothe Christoph Guillaume Daniel Günther Stefan Vasilescu Carmen Gurau Guthke Kersten Haas Judith Harms Lutz Harrower Timothy Hartikainen Päivi Hautecoeur Patrick Havrdova Eva Hellwig Kerstin Hengstman G.J.D. Hermans Mieke Herting Birgit Hodgkinson Suzanne Hoffmann Olaf Hogenesch Roelfien Ida Hognestad Tone Horn Markus Horn Rolf Hupperts R.M.M. N'gbo Rosy Ikazabo N'gbo Ille Olivier Ingvaldsen Teis Barclay Ismail Samir Jacques Francois Jaeger Joachim Jichici Draga Sá Maria José Kafke Waldemar Kallmann Boris Kastnerová Iveta Kausch Ulrich Kendjuo Jean Bertin N. Kermode Allan King John Kirsch Michael Kittlitz Matthias Kneebone Chris Knop Karl Christian Koivisto Keijo Krug Reinhard Kukowski Borries Kwiatkowski Arnaud Landefeld Harald Lang Michael Lange Thomas Larrieu Jean-Marc Lassek Christoph Laureys Guy Lechner-Scott Jeannette López Leonardo Llamas Lund Christian Macdonell Richard MacLean Gregg de Noordhout Alain Maertens Vioud Marcel Maillet Mainella Carolina Malessa Rolf Malkoun Imad Mantegazza Renato Marchetti Paul Mares Jan Ozaeta Gisela Martin Martínez-Yélamos Sergio Marzo Sola María Eugenia Masri Said Mauz Uwe Medaer R. Melin Annick Meluzinová Eva Menges Christian Merienne Marc Meuth Sven Midgard Rune Millefiorini Enrico Molitor Daniel Moll J.W.B. Morganho Armando Moulignier Antoine Myhr Kjell Morten Neudert Christian Nicholas Richard Nifle Chantal Novotna Alena Odeh Francis Ondze Basile Osei-Bonsu Michael Pandolfo Massimo Peeters Katelijne Peglau Ines Ruiz Domingo Pérez Pesci Ilaria Pfeffer Oliver Amato Maria Pia Pilz Christopher Plummer Chris Polzer Udo Pouliquen Andre Aguilar Sandra Quiñones i Torrenta Lluis Ramio Ramo Cristina Rauer Sebastian Redmond Ian Rehkopf Elisabeth Reifschneider Gerd Rente José Retif Cecile Richter Nils Roch Kerstin Roth Roland Rottoli Mariarosa Ruhnke Oliver Ruprecht Klemens Sailer Michael Saines Noel Montero Rosilda Santos Scarel Serena Scarpini Elio Schierenbeck Jürgen Schimrigk Sebastian Schlegel Eugen Schlemilch-Paschen Sylke Schmidt Stephan Schmitz Frank Scholz Peter Schroeter Michael Schuetze Ivo Schüler Stephan Schwab Matthias Schyns-Soeterboek Angélique Seeldrayers Pierrette Seiller Nicolas Sellal François Seppä Juha Matti Shawush Melad Siever Arno Sinnige L.G.F. Skoda Ondrej Smetcoren Charlotte Soares Diana Stankiewicz Tiago SoutoMagdalena Stetkarova Ivana Stienker-Fisse Helmut Stolarikova Klara Stourac Pavel Stratmann Hubert Suárez Sergio Sauri Suceveanu Manuel Tackenberg Björn Thenint Jean Philippe Tiedge Oliver Trojano Maria Tumani Hayrettin Ukkonen Maritta Urbain Etienne Uriot Marie-Sylvie Artaud Ursell Melanie Vachova Marta Valis Martin Walt Anneke Van Der van Munster Caspar Pesch Vincent Van Steenbergen Wilma Van Wijmeersch Bart Van Vanderdonckt Patrick Vanroose Erwin Verhagen W.I.M. Viallet François Wagner Bert Wagner Marc Wersching Ronald Wiehler Stephan Wildemann Brigitte Willekens Barbara Willems Christina Wilson Martin Windsheimer Jörg Zapletalová Olga Ziebold Uwe Ziegler François
[Category] 대상포진,
[Article Type] Original research
[Source] PMC
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