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 19,000 patients with rheumatoid arthritis since 2001. RABBIT-SpA has extended the focus to axial spondyloarthritis and psoriatic arthritis with around 1,700 patients since 2017. With more than 1,500 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 risk calculation based on the individual patient profile. It is accessed over 25,000 times per year.
From our European collaboration with other biologics registers, no increased risk of lymphomas and no shift in lymphoma subtypes associated with TNF inhibitor treatment or other biologics compared to conventional synthetic treatments was found. Following safety concerns, the risk of malignant melanomas was as well analyzed 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 the risk of this severe and life-threatening complication compared to other treatments significantly.
One of the latest findings from RABBIT is that the effectiveness of different biological therapies is influenced differently by obesity, depending on their mode of action. Therapies whose mode of action is based on cytokine inhibition (TNF inhibitors and tocilizumab) are much more strongly affected by obesity than therapies that target the cell level or cell interactions (rituximab and abatacept). This represents a further step towards individualized therapy.
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.
PD Dr.med. Anja Strangfeld
Deputy Group Leader:
PD Dr.med. Anne Regierer
Lisa Baganz 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
Lea Karnstedt, Paula Morgenroth, Ronald Müller, Steve Mvogo Ondoua, Jasmin Sandor, Julia Leskow
Es nehmen ca. 300 rheumatologische Praxen und Kliniken in ganz Deutschland teil./About 300 practices and clinics of rheumatologists in Germany are participating.
Wissenschaftliche Beiräte:/Scientific Advisory Board:
Dr. med. Frank Behrens, Frankfurt am Main; Prof. Dr. med. Jürgen Braun, Herne; PD Dr. med. Rebecca Fischer-Betz, Düsseldorf; Prof. Dr. med. Peter Herzer, München; Prof. Dr. med. Jörn Kekow, Vogelsang-Gommern; Prof. Dr. med. Bernhard Manger, Erlangen; PD Dr. med. Jutta Richter, Düsseldorf; Prof. Dr. med. Georg Schett, Erlangen; Prof. Dr. med. Matthias Schneider, Düsseldorf; Prof. Dr. med. Joachim Sieper, Berlin; Dr. med. Susanna Späthling-Mestekemper, München; Prof. Dr. med. 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)
- Characterising comorbidity in RA in Europe: a multi‐national analysis of big healthcare data (FOREUM grant
- JAK-Pot collaboration (Safety and effectiveness of JAK inhibitors; collaboration with 18 other registers)
- Meissner Y, Strangfeld A, Costedoat-Chalumeau N, Förger F, Goll D, Molto A, Özdemir R, Wallenius M, Fischer-Betz R. European Network of Pregnancy Registers in Rheumatology (EuNeP) – an overview of procedures and data collection.
Arthritis Res Ther 21, 241 (2019) doi:10.1186/s13075-019-2019-3
- Mercer LK, Regierer AC, Mariette X, Dixon WG, Baecklund E, Hellgren K, Dreyer L, Hetland ML, Cordtz R, Hyrich K, Strangfeld A, Zink A, Canhao H, Hernandez MV, Tubach F, Gottenberg JE, Morel J, Zavada J, Iannone F, Askling J, Listing J. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project. Ann Rheum Dis. 2017; 76(12):2025-2030.
- Mercer LK, Askling J, Raaschou P, Dixon WG, Dreyer L, Hetland ML, Strangfeld A, Zink A, Mariette X, Finckh A, Canhao H, Iannone F, Zavada J, Morel J, Gottenberg JE, Hyrich KL, Listing J. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis. 2017; 76(2):386-391.
- Meissner Y, Richter A, Manger B, Tony HP, Wilden E, Listing J, Zink A, Strangfeld A. Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort. Ann Rheum Dis. 2017; 76(9):1583-1590.
- Strangfeld A, Richter A, Siegmund B, Herzer P, Rockwitz K, Demary W, Aringer M, Meissner Y, Zink A, Listing J. Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis. 2017; 76(3):504-510.
- Baganz L, Richter A, Kekow J, Bussmann A, Krause A, Stille C, Listing J, Zink A, Strangfeld A. Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified by number of previous treatment failures with biologic agents: results from the German RABBIT cohort. Rheumatol Int. 2018; 38(4):579-587.