Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)
Authors: Tony Hans-Peter , Burmester Gerd , Schulze-Koops Hendrik , Grunke Mathias , Henes Joerg , Kötter Ina , Haas Judith , Unger Leonore , Lovric Svjetlana , Haubitz Marion , Fischer-Betz Rebecca , Chehab Gamal , Rubbert-Roth Andrea , Specker Christof , Weinerth Jutta , Holle Julia , Müller-Ladner Ulf , König Ramona , Fiehn Christoph , Burgwinkel Philip , Budde Klemens , Sörensen Helmut , Meurer Michael , Aringer Martin , Kieseier Bernd , Erfurt-Berge Cornelia , Sticherling Michael , Veelken Roland , Ziemann Ulf , Strutz Frank , von Wussow Praxis , Meier Florian MP , Hunzelmann Nico , Schmidt Enno , Bergner Raoul , Schwarting Andreas , Eming Rüdiger , Hertl Michael , Stadler Rudolf , Schwarz-Eywill Michael , Wassenberg Siegfried , Fleck Martin , Metzler Claudia , Zettl Uwe , Westphal Jens , Heitmann Stefan , Herzog Anna L , Wiendl Heinz , Jakob Waltraud , Schmidt Elvira , Freivogel Klaus , Dörner Thomas ,   GRAID investigators
Published: May 2011

Abstract
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).

Conclusions
Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.