Long term effectiveness of biological use for rheumatoid arthritis in daily clinical practice: analyses on the DREAM registry

The Dutch Rheumatoid Arthritis Monitoring (DREAM) biological register was started in February 2003 with the aim to monitor and evaluate the effectiveness of biologic agents in daily clinical practice. To-date, data on approximately 2000 patients is instantly available for analyses. Experience with long term use of biologics (especially TNF inhibitors (TNFi)) in the treatment of RA has raised some new questions which can be explored in the DREAM biologic registry. Based on current knowledge on antibody formation against TNFi, we hypothesize that if there are no anti-bodies formed against etanercept while antibodies are formed against adalimumab and infliximab, the latter two TNFi will potentially be less effective than etanercept in the long term. Therefore, we aim to make a comparison of the 5-year effectiveness and drug survival of three TNFi, adalimumab, etanercept and infliximab, controlled for relevant confounders. Although it is advised to treat patients with methotrexate (MTX) as co-medication because of synergistic effects on effectiveness and it’s assumed inhibition of the formation of anti-bodies against TNFi, there is still a body of patients that is treated with TNFi mono-therapy (about 15%). We expect a difference in effectiveness and drug survival between mono-therapy (TNFi) and combination therapy (TNFi + MTX), which might have an effect on the cost-effectiveness of TNFi. This will be analysed by comparing TNFi mono-therapy with TNFi + MTX combination therapy, controlled for relevant confounders. There is still lack of evidence that could guide the choice between subsequent biologic agents after failure on at least one TNFi. Per biologic agent we will analyse whether the type or number of agents used before the specific biologic agent is associated with the effectiveness of the agents. Analyses will be performed as separate case-control studies. Cases are defined as EULAR responders and controls are defined as EULAR non-responders. Cases and controls can be compared on their treatment histories and odds ratios will be calculated. For all three analyses, data from the DREAM registry will be used. This is a high quality observational registry in which unselected data is gathered on effectiveness, long-term side effects and use in daily clinical practice. The DREAM registry delivers information on safety and effectiveness in unselected real world patients, including elderly patients and patients with multi-morbidity and using co-medication. Moreover, real world data are able to feed health technology assessments and have additional value for formulating guidelines and raising awareness among professionals on the way they use (expensive) drugs. Besides, many research questions cannot be answered in a RCT. We first learn from experience in daily clinical practice and then use these results to formulate hypotheses and designs for future (pragmatic) randomized trials. In this way, future trials will best meet the needs of rheumatologists in daily practice. The DREAM registry is the heart of the DREAM collaboration in which the UMC st Radboud and University Twente/ Medisch spectrum Twente and 11 other rheumatology clinics are bonded. Within the DREAM collaboration we created an academic environment in which research is used to improve quality of care by doing research projects based on clinical experience and translating research findings back to clinical practice. This increases the input from the clinical point of view and the implementation of results into daily clinical practice. Ultimately we use results from DREAM analyses to update the treatment guidelines which are used in DREAM centres. DREAM provides transparency on treatment results and offers the DREAM centres a platform for improvement of their quality of care through online benchmarking information regarding their performances compared to other DREAM hospitals and through the identification of best practices.