Objectives Developing and evaluating new treatment guidelines for rheumatoid arthritis (RA) based on observational data requires a quantitative understanding of patterns in current treatment practice with biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Methods We used data from the CorEvitas RA registry to study patients starting their first b/tsDMARD therapy—defined as the first line of therapy—between 2012 and the end of 2021. We identified treatment patterns as unique sequences of therapy changes following and including the first-line therapy. Therapy cycling was defined as switching back to a treatment from a previously used therapeutic class. Results 6,015 b/tsDMARD-naïve patients (77% female) were included in the analysis. Their median age was 58 years, and their median disease duration was 3 years. In 2012–2014, 80% of the patients started a tumor necrosis factor inhibitor (TNFi) as their first b/tsDMARD. However, the use of TNFi decreased in favour of Janus kinase inhibitors (JAKi) since 2015. While the number of treatment patterns was large, therapy cycling was relatively common. For example, 601 patterns were observed among 1133 patients who changed therapy at least four times, of whom 85.3% experienced therapy cycling. Furthermore, the duration of each of the first three lines of therapy decreased over the past decade. Conclusion First-line therapy was almost always TNFi, but diversity in treatment choice was high after that. This practice variation allows for proposing and evaluating new guidelines for sequential treatment of RA. It also presents statistical challenges to compare subjects with different treatment sequences.