Assessing benefits and risks of new treatments in rheumatology
The mission of our group is to provide robust data on the real-world safety and effectiveness of new therapies in rheumatology. This objective is addressed through three long-term cohort studies, so-called disease registers. RABBIT has enrolled more than 18,000 patients with rheumatoid arthritis since 2001. RABBIT-SpA has extended the focus to axial spondyloarthritis and psoriatic arthritis with around 1,200 patients since 2017. With nearly 1,400 women, Rhekiss is one of the largest pregnancy registers in rheumatology worldwide, with an extensive observation period reaching from pre-conception to the second birthday of the child. In order to enable joint analyses with even larger data sets, we coordinate the European Network of Pregnancy Registers EuNeP, funded by the FOREUM foundation.
Data from these registers provide clinicians with reliable information on the outcomes of treatments in different groups of patients. An example is the RABBIT risk score for serious infection which takes into account patient characteristics, medical history, co-morbidity, treatment of interest, as well as concomitant treatment. A web-based risk calculator (www.biologika-register.de) allows immediate calculation of risk. It has been accessed approximately 25,000 times in 2018.
From our European collaboration with other biologics registers, no increased risk of lymphomas and no shift in lymphoma subtypes associated with the treatment with TNF inhibitors or other biologics compared to conventional synthetic treatments was found. Following safety concerns, the risk of malignant melanomas was as well analysed in this collaboration, leading to the reassuring result of no increased risk with TNF inhibitor treatment.
Overall, the results from RABBIT underline the importance of tight control of disease activity. Uncontrolled high disease activity was shown to be a major driver of preterm mortality, myocardial infarction and stroke.
Due to the high numbers of patients and patient-years, the registers also allow for the investigation of very rare events, such as lower intestinal perforations. For the first time outside of Randomised Clinical Trials, interleukin-6 blockade has been shown to increase (at least fivefold) the risk of this severe and life-threatening complication compared to other treatments.
Future analyses will address spondyloarthritides and pregnancies, as well as new treatment options such as biosimilars and JAK inhibitors, taking the interplay of risks arising from the disease itself, conditions of the patient including comorbidity, and the novel treatments into account. This will allow tailoring treatment to the risk profiles of individual patients.
Keywords: Disease Register, observational cohort, long-term safety and effectiveness
Dr.med. Anja Strangfeld
Deputy Group Leader:
PD Dr.med. Anne Regierer
Lisa Baganz MSc, Dörthe Kühl-Habich MSc, Dr. Doreen Huschek, Dr. rer. med. Yvette Meißner, Dr. rer. nat. Martin Schäfer, Anja Weiß MSc
Medical documentalists/Data manager:
Tanja Ellmann, Mandy Grope, Juliana Hoffmann, Ulrike Kamenz, Lisa Lindner, Steffen Meixner, Andreas Reich, Juliane Reinke, Franca Stein, Carina Wittkopp, Corina Walter, Birgit Wuthe, Susanna Zernicke, Steffi Zühlke
Claudia Fritz, Siegfried Kindler, Dina Schreckeis,
Madlen Spilka, Ronja Ramien
Martin Schütz, Lea Karnstedt, Paula Morgenroth, Ronald Müller, Steve Mvogo Ondoua, Jasmin Sandor, Michelle Pieper, Julia Leskow
About 300 practices and clinics of rheumatologists in Germany are participating.
Scientific Advisory Board:
Dr. Frank Behrens, Frankfurt am Main; Prof. Jürgen Braun, Herne; PD Dr. Rebecca Fischer-Betz, Düsseldorf; Prof. Peter Herzer, München; Prof. Jörn Kekow, Vogelsang-Gommern; Prof. Bernhard Manger, Erlangen; PD Dr. Jutta Richter, Düsseldorf; Prof. Georg Schett, Erlangen; Prof. Matthias Schneider, Düsseldorf; Prof. Joachim Sieper, Berlin; Dr. Susanna Späthling-Mestekemper, München; Prof. Christof Specker, Essen
BSRBR (Manchester, GB), ARTIS (Stockholm, S), DANBIO (Kopenhagen, DK), BIOBADASER (Madrid, E), RATIO (Paris, F), AIR (Montpellier, F), ORA (Straßburg, F), REGATE (Straßburg, F), ATTRA (Prag, CZ), GISEA (Bari, I), SCQM (Genf, S), Rheuma.pt (Lissabon, P)
EULAR Working Group RODS (Register and Observational Drugs Studies), ENCePP (European Network of Centers of Pharmacovigilance and Pharmacoepidemiology), EuNeP (European Network of Pregnancy Registers in Rheumatology)
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