Rheumatoid Arthritis & Comorbidities: Treat to Target

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting approximately 0.5 1% of the population. Due to its chronicity and its destructive disease course, RA leads to a major reduction in physical function, quality of life (QoL) and work productivity. In recent years treatment strategies have been proposed aiming for remission or low disease activity. Nevertheless, when compared to healthy controls, patients with RA continue to show substantial impairment of physical function and quality of life, as well as reduced productivity. This is partially due to the direct effects of RA, but prevalent comorbid conditions may also affect outcomes in patients with RA. An effective RA treatment strategy aiming for best achievable outcomes needs to not only be directed to RA, but also to comorbidities associated with RA. Treating RA to an ultimate functional and quality of life target therefore needs a multidisciplinary concept, similarly encompassing the evaluation, consideration, and treatment of comorbidities in RA patients. OBJECTIVE: The aim of the present proposal is to evaluate the prevalence of comorbidities, the effect of comorbidities on disease activity, physical function, quality of life, and work productivity in RA, and by how much effective treatment of comorbidities may reduce this burden. METHODS: To answer the question we first will systematically assess the comorbidity profile of contemporary RA patients by initially investigating the prevalence and incidence of comorbidities in a large dataset. In a next step we plan to evaluate the association of comorbidities and activity of RA and quantify the impact of each of these comorbid conditions on physical function, quality of life, and work productivity using datasets with detailed clinical data. This will provide information about the impact of each comorbid condition, as well as the cumulative effect of multiple comorbidities. The results will be used to model the effect of treating comorbidities on the individual patient as well as on society by evaluation of cost-effectiveness in a decision analysis model. EXPECTED OUTCOMES: The overall results will provide highly pertinent information about the impact of the comorbid conditions on major socio-economic outcomes in RA patients, as well as allow one to adapt treatment strategies including therapy of comorbidities, to improve all important outcomes of Rheumatoid Arthritis.

Summary for public relations work In rheumatoid arthritis (RA) patients a high prevalence of co-existing conditions can be observed, probably due to the chronic and inflammatory character of the disease. In recent years, increasing attention has been paid to comorbidities and multimorbidity as clinicians in rheumatology care for an aging patient population with multiple diseases. However, in contrast to comorbidities, the concept of multimorbidity is poorly understood and not well integrated into research and care. In our project we were able to develop and validate an instrument to quantify the burden of multimorbidity and to control for the effect on patients overall well being. We were able to identify the impact of multimorbidity status on patients treatment and outcomes. At the beginning of the project we were focusing on the conceptual differences between comorbidity and multimorbidity and on implementing the concept of multimorbidity in rheumatology. To quantify the impact of multimorbidity on patients overall well-being we developed a multimorbidity index based on health related quality of life, using a RA cohort. The index was used for further projects to study the effect of multimorbidity status on treatment patterns and outcomes in RA patients, which was the aim of our project. Concomitant diseases might impact treatment strategies, as multimorbid patients may observe less intensive treatment of RA than indicated. This could cause higher activity of RA and therefore has a negative impact on all its major outcomes, such as physical function, quality of life, work productivity or even mortality. In a large, international cohort we could show that after accounting for disease activity and other important confounders, the odds of biological DMARD use decreases 11% for each additional chronic morbid condition. This would mean that patients with a high number of chronic conditions in addition to RA were less likely to receive a biological agent, even if it might be necessary due to high disease activity of RA. Furthermore, we could also demonstrate that the multimorbidity negatively impacts treatment response in RA patients initiating DMARD therapy. The odd of achieving remission one year after DMARD start decreased 28% per additional condition. Multimorbid RA patients did not only miss the treatment target but had also worse outcomes such as lower physical function.Our findings are important to consider when treating multimorbid RA patients, as it might be necessary to define new treatment targets and strategies in this group of patients.