Many studies have been conducted concerning discontinuation of biologic disease-modifying anti-rheumatic drugs (DMARD), but mainly in trial settings which result in limited generalisability. Registry studies can complement the current literature of biologic DMARD discontinuation by providing more generalisable information. However, it may be necessary to combine registries to increase power and provide more diverse patient populations. This increased power could provide us information about risk and benefits of discontinuing biologic DMARD in typical clinical practice. However, use of multiple registries is not without challenges. In this review, we discuss the challenges to combining data across multiple registries, focusing on biologic discontinuation as an example. Challenges include: 1) generalizability of each registry; 2) new versus prevalent users designs; 3) outcome definitions; 4) different health care systems; 5) different follow up intervals; and 6) data harmonisation. The first three apply to each registry, and the last three apply to combining multiple registries. This review describes these challenges, corresponding solutions, and potential future opportunities.