Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with chronic articular pain, disability and excess mortality. There has been a growing emphasis on diagnosing and treating RA early and intensively with the goal of minimizing disability and mortality. The introduction of biologics in the past decade has revolutionized the treatment of RA because of their substantial impact on disease signs and symptoms as well as their ability to slow radiographic progression of joint damage. However, cost and safety concerns continue to be important considerations as these agents are used by an increasing number of patients, particularly those with less severe disease and with a greater burden of comorbidities than typically represented in randomized clinical trials (RCTs). Additionally, comparative effectiveness research is becoming increasingly important, and RCTs are unlikely to provide answers to many important comparative effectiveness questions.
To complement information obtained from RCTs, various observational cohorts and registries have been established in the last decade for patients with rheumatic diseases. A cohort is a structured organization of patients; as one type of cohort, a registry is typically prospective and enrolls patients for a specific reason (1
). The registries are either drug based (i.e. patient enrolled if they are starting particular medications) or disease based (i.e. enrollment is predicated on a patient have a particular diagnosis such as RA), or both, and most allow evaluation of outcomes referent to a comparator group of RA patients. Many but not all drug-based registries enroll patients treated with a variety of medications for a given disease such as RA. In addition to broadly studying disease-related outcomes, an important purpose of most rheumatic disease registries is to monitor the long term effectiveness and safety of new therapies. These registries are designed as longitudinal cohorts and can compare, for example, biologic users to non-biologic users or to national population registers in a comparator arm. Many registries have unique features, such as a link to a national death database, bio-repositories, or access to laboratory data that makes them particularly suited to answer certain research questions. Some of the cohorts have reported results with differing magnitudes of effect or seemingly discrepant conclusions for the same safety questions. A careful comparison of the characteristics (similarities and differences) of these rheumatologic registries can lead to a better understanding of the reasons that may sometimes underlie heterogeneous results.
In this article, we present published and unpublished data to allow a qualitative comparison across European and U.S. RA registries and cohorts. The purpose of this approach was four-fold: 1) To compare and contrast how similar information is collected and reported by the different registries, 2) To highlight the unique features of registries, the consequence of which results in certain registries being able to answer particular types of research questions; 3) To compare outcomes reported by the various registers; and 4) To explore how differences in registry design and analytic approaches may impact their results. In achieving these four goals, we compared registries across the domains of 1) recruitment methods and inclusion criteria for both biologic and comparator cohort patients; 2) demographics and comorbidities; 3) outcomes such as effectiveness and medication persistence; 4) safety; in particular, the rate of serious infections, acute myocardial infarction and malignancy. Recognizing that harmonization of analytic approaches may improve the ability to compare result across registries, inherent differences in registry populations and the design features of the registry may provide results that are generalizable only to specific RA populations, a topic also addressed in this manuscript.