Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial
2017; Elsevier BV; Volume: 17; Issue: 1 Linguagem: Inglês
10.1016/s1474-4422(17)30378-2
ISSN1474-4465
AutoresIvo N. van Schaik, Vera Bril, Nan van Geloven, Hans‐Peter Hartung, Richard A. Lewis, Gen Sobue, John‐Philip Lawo, Michaela Praus, Orell Mielke, Billie L. Durn, David R. Cornblath, Ingemar S. J. Merkies, Arman Sabet, Koshy George, L. Jackson Roberts, Ross Carne, Stefan Blum, Robert D. Henderson, Philip Van Damme, Jelle Demeestere, Sandrine Larue, Catherine-Andree Pinard D'Amour, Vera Bril, Ari Breiner, Pavel Kunc, Martin Vališ, J Süssová, Tomas Kalous, Radomír Taláb, Michal Bednar, Toomas Toomsoo, Inna Rubanovits, Katrin Gross‐Paju, Ulvi Sorro, M. Saarela, Mari Auranen, Jean Pouget, Shahram Attarian, Gwendal Le Masson, Anne-Cécile Wielanek-Bachelet, Claude Desnuelle, Émilien Delmont, Pierre Clavelou, D Aufauvre, Jens Schmidt, Jana Zschuentssch, Claudia Sommer, Daniela Kramer, Olaf Hoffmann, Carsten Goerlitz, Jürgen Haas, Marko Chatzopoulos, Richard S. Yoon, Ralf Gold, Peter Berlit, Andrea Jaspert-Grehl, David Liebetanz, Anna Kutschenko, Martin Stangel, Corinna Trebst, Petra Baum, Florian Then Bergh, Juliane Klehmet, Andreas Meisel, Fabian Klostermann, Johanna Oechtering, Helmar C. Lehmann, Michael Schroeter, Tim Hagenacker, Daniel Mueller, A.D Sperfeld, F. Bethke, Vivian E. Drory, Avi A. Algom, David Yarnitsky, Beth B. Murinson, Antonio Di Muzio, Fausta Ciccocioppo, Sandro Sorbi, Sabrina Matà, Angelo Schenone, Marina Grandis, Giuseppe Lauria, Daniele Cazzato, Giovanni Antonini, Stefania Morino, Dario Cocito, Maurizio Zibetti, Takanori Yokota, Takuya Ohkubo, Takashi Kanda, M Kawai, Kenichi Kaida, Hiroyuki Onoue, Satoshi Kuwabara, Masahiro Mori, Masahiro Iijima, Ken Ohyama, Masayuki Baba, Masahiko Tomiyama, Kazutoshi Nishiyama, Tsugio Akutsu, Kazuhito Yokoyama, Kazuaki Kanai, Ivo N. van Schaik, Filip Eftimov, Nicolette C. Notermans, Nora A. Visser, Catharina G. Faber, Janneke G. J. Hoeijmakers, Konrad Rejdak, Urszula Chyrchel-Paszkiewicz, Carlos Casanovas Pons, Maria Alberti Aguilo, Josep Gámez, Maria Salvadó Figueras, C. Márquez Infante, S. Benítez Rivero, Michael P. Lunn, Jasper M. Morrow, David Gosal, Timothy Lavin, Isaac Melamed, Alessandro Testori, Senda Ajroud‐Driss, Daniela M. Menichella, Ericka Simpson, Eugene C. Lai, Mazen M. Dimachkie, Richard J. Barohn, Said R. Beydoun, Harpreet K Johl, Dale J. Lange, Alexander Shtilbans, Suraj Muley, Shafeeq Ladha, Miriam Freimer, J. T. Kissel, Norman Latov, Russell L. Chin, Eroboghene E. Ubogu, Sandi Mumfrey, TRamesh Kumar Rao, Paul C. MacDonald, Khema R. Sharma, G. Gonzalez, Jeffrey A. Allen, David Walk, Lisa D. Hobson‐Webb, Karissa Gable,
Tópico(s)Myasthenia Gravis and Thymoma
ResumoApproximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo.Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076.In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50-74]) patients on placebo, 22 (39% [27-52]) on low-dose SCIg, and 19 (33% [22-46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25% (95% CI 6-41) for low-dose versus placebo (p=0·007), 30% (12-46) for high-dose versus placebo (p=0·001), and 6% (-11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related.This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP.CSL Behring.
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