Ludwig Kappos

Publications (336) View all

• Source

  Available from: Ludwig Kappos

  Dataset: BG12 reduces evolution

  G N O'Neill, K Dawson, K Schmierer, D H Miller, L Kappos, R Gold, E Havrdova, M Yang, E Meluzinova, D G MacManus, M Eraksoy, V Limmroth, M Dufek, T A Yousry, C H Polman
• Source

  Available from: David G Macmanus

  Dataset: J Neurol (2011) 258:449–456 BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis.

  D G MacManus, D H Miller, L Kappos, R Gold, E Havrdova, V Limmroth, C H Polman, K Schmierer, T A Yousry, M Eraksoy, E Meluzinova, M Dufek, M Yang, G N O'Neill, K Dawson
• Article: Six-year follow-up of a case series with non-communicating syringomyelia in multiple sclerosis.

  K Weier, Y Naegelin, M Amann, S Magon, N Mueller-Lenke, E-W Radue, L Kappos, C Stippich, A Gass, T Sprenger
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  ABSTRACT: BACKGROUND: Non-communicating syringomyelia (NCS) has occasionally been described in case reports and small case series as an incidental finding of spinal cord (SC) pathology in patients with multiple sclerosis (MS), but only little is known on the clinical course and progression of NCS, and in more general terms on the prognosis of patients with MS and NCS. METHODS: Nine patients with MS with known NCS at baseline and a control group of 18 age-, sex- and disease course-matched patients with MS without NCS were recruited for a follow-up visit after 6 years. All 27 patients underwent clinical examination and brain magnetic resonance imaging (MRI), and 8/9 patients with NCS were additionally studied with MRI of the SC. MRI data were analysed for changes in length and maximal cross-sectional area of the NCS, lesion volumes of the brain and cord as well as for volumetric metrics of the whole brain (using SIENAX), the cerebellum and medulla oblongata (using ECCET). RESULTS: NCS did not significantly change in size when corrected for multiple comparisons. The clinical data (annual relapse rate, EDSS and disease duration) and MRI metrics (T2 and T1 lesion load; whole brain, cerebellar and medulla oblongata volumes as well as their percentage volume change per year) did not significantly differ between patients with MS with or without NCS. CONCLUSION: The stable findings regarding size and shape of the syrinx and lack of distinguishing MRI and clinical features support the assumption that NCS is not defining a prognostically or pathogenetically distinct subgroup of patients with MS.
  European Journal of Neurology 12/2012; · 3.69 Impact Factor
• Article: Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.

  M S Freedman, J S Wolinsky, B Wamil, C Confavreux, G Comi, L Kappos, T P Olsson, A Miller, H Benzerdjeb, H Li, C Simonson, P W O'Connor
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  ABSTRACT: To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFNβ alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [p = 0.4355] and 57.9% [p = 0.1005] for 7 and 14 mg, respectively). Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. Classification of evidence: This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.
  Neurology 05/2012; 78(23):1877-85. · 8.31 Impact Factor
• Article: Multiple Sklerose Aktuelle Übersicht zu fehlgeschlagenen und abgebrochenen Therapiestudien

  H. Wiendl, O. Neuhaus, L. Kappos, R. Hohlfeld
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  ABSTRACT: Neue immunbiologische Erkenntnisse haben zusammen mit Fortschritten in der Biotechnologie, Verbesserungen im Design von Medikamentenstudien und Entwicklung der Kernspintomographie zu einer Vielfalt prüfbarer Therapieansätze bei der multiplen Sklerose geführt. Neben erfolgreichen immunmodulatorischen Therapien gibt es jedoch einige Fehlschläge: Trotz eindrucksvoller tierexperimenteller Daten, überzeugender Konzepte oder gar Erfolg versprechender Phase-I/II-Studien erbrachten die untersuchten Medikamente letztendlich keine positive Wirkung oder zeigten unerwartete schwere Nebenwirkungen. Dieser Artikel gibt eine aktuelle Zusammenstellung von Therapiestudien, die fehlgeschlagen sind oder aus anderen Gründen abgebrochen wurden. Im Zentrum steht die Blockierung des TNF-α, die in 2 Studien (Lenercept, Infliximab) sogar zu negativen Effekten geführt hatte. Diese Resultate werfen kritische Fragen bezüglich Läsionspathogenese und Wertigkeit der Kernspintomographie in der Beurteilung klinischer Therapieeffekte auf. Außerdem werden die Studien für die immunsuppressiven Agenzien Linomid, Deoxyspergualin, Sulfasalazin und Cladribin, für die Zytokine Interleukin-10 und TGF-β2, die Studien zur Remyelinisierung durch intravenöse Immunglobuline (IVIg), zur oralen Toleranzinduktion und zur extrakorporalen Photopherese diskutiert. Recent immunobiological findings together with advances in biotechnology, ameliorations in clinical trial design, and MRI developments have led to a variety of therapeutical approaches in multiple sclerosis (MS). However, in contrast to successfully introduced new treatments, a number of therapeutical failures exist as well: despite impressive data from animal models, convincing concepts, and promising phase I/II studies, some investigated drugs and strategies showed no positive effects in clinical trials, or trials had to be terminated because of unexpected side effects. This article provides an overview of clinical studies that have failed or been abandoned for other reasons. Tumor necrosis factor (TNF) α-antagonists which have led to negative effects in two studies (Lenercept, Infliximab) are discussed in detail. These results raise critical questions concerning the hypothetical pathogenesis of MS lesions and the value of MRI in the assessment of clinically relevant therapeutic drug effects. In addition to a description of the immunobiological background, studies on the immunosuppressive agents linomide, deoxyspergualin, sulfasalazine and cladribine, trials for the cytokines interleukin-10 and TGF-β2, the studies on remyelination by intravenous immunoglobulins (IVIg), oral tolerance, and extracorporeal photopheresis are discussed.
  Der Nervenarzt 04/2012; 71(8):597-610. · 0.68 Impact Factor