TY  - JOUR
A1  - Tony, Hans-Peter
A1  - Burmester, Gerd
A1  - Schulze-Koops, Hendrik
A1  - Grunke, Mathias
A1  - Henes, Joerg
A1  - Kötter, Ina
A1  - Haas, Judith
A1  - Unger, Leonore
A1  - Lovric, Svjetlana
A1  - Haubitz, Marion
A1  - Fischer-Betz, Rebecca
A1  - Chehab, Gamal
A1  - Rubbert-Roth, Andrea
A1  - Specker, Christof
A1  - Weinerth, Jutta
A1  - Holle, Julia
A1  - Müller-Ladner, Ulf
A1  - König, Ramona
A1  - Fiehn, Christoph
A1  - Burgwinkel, Philip
A1  - Budde, Klemens
A1  - Sörensen, Helmut
A1  - Meurer, Michael
A1  - Aringer, Martin
A1  - Kieseier, Bernd
A1  - Erfurt-Berge, Cornelia
A1  - Sticherling, Michael
A1  - Veelken, Roland
A1  - Ziemann, Ulf
A1  - Strutz, Frank
A1  - von Wussow, Praxis
A1  - Meier, Florian MP
A1  - Hunzelmann, Nico
A1  - Schmidt, Enno
A1  - Bergner, Raoul
A1  - Schwarting, Andreas
A1  - Eming, Rüdiger
A1  - Schwarz-Eywill, Michael
A1  - Wassenberg, Siegfried
A1  - Fleck, Martin
A1  - Metzler, Claudia
A1  - Zettl, Uwe
A1  - Westphal, Jens
A1  - Heitmann, Stefan
A1  - Herzog, Anna L.
A1  - Wiendl, Heinz
A1  - Jakob, Waltraud
A1  - Schmidt, Elvira
A1  - Freivogel, Klaus
A1  - Dörner, Thomas
A1  - Hertl, Michael
A1  - Stadler, Rudolf
T1  - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)
JF  - Arthritis Research & Therapy
N2  - Introduction: 

Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. 

Methods: 

Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. 

Results: 

A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm)
KW  - GRAID
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856
VL  - 13
IS  - R75
ER  - 
TY  - JOUR
A1  - Kleinschnitz, Christoph
A1  - Grund, Henrike
A1  - Wingler, Kirstin
A1  - Armitage, Melanie E.
A1  - Jones, Emma
A1  - Mittal, Manish
A1  - Barit, David
A1  - Schwarz, Tobias
A1  - Geis, Christian
A1  - Kraft, Peter
A1  - Barthel, Konstanze
A1  - Schuhmann, Michael K.
A1  - Herrmann, Alexander M.
A1  - Meuth, Sven G.
A1  - Stoll, Guido
A1  - Meurer, Sabine
A1  - Schrewe, Anja
A1  - Becker, Lore
A1  - Gailus-Durner, Valerie
A1  - Fuchs, Helmut
A1  - Klopstock, Thomas
A1  - de Angelis, Martin Hrabe
A1  - Jandeleit-Dahm, Karin
A1  - Shah, Ajay M.
A1  - Weissmann, Norbert
A1  - Schmidt, Harald H. H. W.
T1  - Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration
N2  - Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.
KW  - Schlaganfall
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68416
ER  -