GRAID – Interim Analysis Of The Retrospective German Register In Autoimmune Diseases

Thomas Dörner¹, Enno Schmidt², Christoph Fiehn³, Frank Behrens⁴, Rebecca Fischer-Betz⁵, Martin Fleck⁶, Julia Holle⁷, Joerg C. Henes⁸, Annett M. Jacobi⁹, Christian Kneitz¹⁰, Esther Wittenborn¹¹, Fabian Proft¹², Hendrik Schulze-Koops¹³ and Christof Iking-Konert¹⁴, ¹CC12, Dept. Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany, ²Department of Dermatology, University of Lübeck, Lübeck, Germany, ³ACURA Centre for Rheumatic Diseases, Baden-Baden, Germany, ⁴CIRI/Div. Rheumatology, J.W. Goethe-University, Frankfurt/Main, Germany, ⁵Department of Rheumatology, University of Düsseldorf, Düsseldorf, Germany, ⁶Internal Medicine I, University Medical Center of Regensburg, Regensburg, Germany, ⁷Vasculitis Clinic, Klinikum Bad Bramstedt & University Hospital of Schleswig Holstein, Bad Bramstedt, Germany, ⁸Department of Internal Medicine II, Rheumatology Division, University Hospital Tuebingen, Tuebingen, Germany, ⁹Rheumatology Internal Medicine D, University Hospital Münster, Münster, Germany, ¹⁰Internal Medicine II, Hospital Südstadt, Rostock, Germany, ¹¹Roche Pharma AG, Grenzach-Wyhlen, Germany, ¹²Rheumaeinheit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany, ¹³Division of Rheumatology, University of Munich, Munich, Germany, ¹⁴Department of Rheumatology, University Hospital Hamburg Eppendorf, Hamburg, Germany

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Biologics, off-label prescribing, registries and safety

Session Information

Title: Miscellaneous Rheumatic and Inflammatory Diseases II: Miscellaneous Rheumatic Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose: Autoimmune diseases are characterized by high morbidity and lead frequently to physical disability and loss of income. They are the third most important disease group following cardiovascular and tumour diseases. Beyond clinical studies the GRAID registry evaluates primarily safety aspects of the use of all biological therapies in clinical routine off-label settings.

Methods: Following GRAID1, GRAID2 is a retrospective, non-interventional multicentre registry using online data collection starting 2010. Whereas GRAID1 included only rituximab therapies, in GRAID2 all patients with an initial off-label-treatment with biologics since August 2006 can be enrolled. The retrospective documentation comprises case history, diagnosis, course of disease including safety and global efficacy.

Results: While GRAID1 included 370 patients, the interim analysis of GRAID2 is based on additional 125 patients (mean age 47.4 years; 62.4% female) refractory to conventional therapies covering 119.2 patient years (py) of biologics therapy up to now. As in GRAID1 the most frequent diagnosis was systemic lupus erythematosus (SLE; GRAID1 23.0%, GRAID2 20.0%). Further diagnoses in GRAID2 were ANCA associated vasculitides (AAV; 16.0%), overlap syndromes (8.0%), arthritis (non-RA/ankylosing spondylitis/psoriasis arthritis; 7.2%), fever syndromes (6.4%), progressive systemic sclerosis (3.2%), Sjögren’s syndrome (3.2%), macrophage activation syndrome (3.2%), polymyalgia rheumatica/cranial arteritis (2.4%), poly-/dermatomyositis (1.6%) and cryoglobulinaemic vasculitis (0.8%). Other main diagnoses were found in 28.0%. Main pre-treatments comprised steroids (69.6%) and azathioprine (50.4%). Most frequent biologics used were rituximab (71.2%), tocilizumab (12.0%), infliximab (8.0%), anakinra (3.2%), adalimumab (1.6%) and certolizumab (0.8%). In SLE and AAV rituximab was the only therapy used and in overlap syndromes it was most frequently used (90.0%). In arthritis and fever syndromes tocilizumab was applied most frequently (55.6% and 50.0%, resp.). After 6-7 months, data were available for 21/89 rituximab patients incl. 13 patients (61.9%) with general symptoms as clinical manifestation: Complete remission found in 3/13 patients (23.1%), partial remission in 4/13 patients (30.8%) and no substantial change in 6/13 patients (46.2%). After first application the tolerability of biologics was assessed as “very good”/”good” by physicians in 92.8% of patients. Altogether, 110 adverse events (AEs) occurred in 44 patients incl. 20 infections in 17 patients representing a rate of 16.8/100 py. 4 serious infections were reported, representing a rate of 3.4/100 py. In total, 12 serious AEs were reported in 8 patients. 2 patients (1.6%) died (pneumonia fungal and leukaemia).

Conclusion: GRAID1 has shown that off-label therapy with rituximab can be effective and well-tolerated in several autoimmune diseases. As data on off-label use are valuable to get data on therapeutic options for patients in urgent need, GRAID2 continues to collect data of a broader range of biologics and autoimmune diseases. Up to now, the data indicate benefits for the patients as well and safety results corresponding to GRAID1.

Disclosure:

T. Dörner,

Roche/Chugai,

Sanofi-Aventis Pharmaceutical,

UCB,

Roche/Chugai,

Takeda,

E. Schmidt,
None;

C. Fiehn,

Speakers fees <3000 Euro/year, 9; F. Behrens,
None;

R. Fischer-Betz,
None;

M. Fleck,
None;

J. Holle,

Roche/Chugai,

J. C. Henes,
None;

A. M. Jacobi,
None;

C. Kneitz,
None;

E. Wittenborn,

Roche Pharma AG,

F. Proft,
None;

H. Schulze-Koops,

BMS, Novartis, CSL Behring,

Abbott, Abbvie, Actelion, AstraZeneca, Biotest, BMS, Celgene, Chugai, GSK, Hoffmann-La Roche, MSD, Medac, Merck, Mundi Pharma, Novartis, Nycomed, Pfizer, Roche, Savient, UCB, 4SC ,

C. Iking-Konert,
None.

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