There are no clinically meaningful differences between bio-originators (BO) and their biosimilars (BS) in safety and efficacy. However, differences in pharmaceutical properties, such as volume and excipient, can occur. This study aimed to compare outcomes between patients transitioning from the modernized adalimumab BO (0.4 mL/no citrate) to BS1 (0.8 mL/citrate) and from BS1 to BS2 (0.4 mL/no citrate) and outcomes for new starters. In this retrospective exploratory cohort study of RA, PsA, and axial SpA patients receiving adalimumab, the (adjusted) 12-month drug survival rates were compared between the transition from the modernized BO to BS1 (Cohort 1, 2021) and from BS1 to BS2 (Cohort 2, 2023) in existing users, and for adalimumab-naïve new starters of the originator and BS1 and BS2 (Cohorts 3 to 5). Subanalyses included drug survival separately for inefficacy and intolerability. In existing users, 983 patients transitioned to BS1, 1082 patients to BS2, with 659 patients in both cohorts. Drug survival rates at 12 months were 73% (95% CI: 70-76) and 90% (95% CI: 88-92), respectively (P < 0.001), adjusted hazard rate ratio (HRR) 0.32 (95% CI: 0.26-0.40) in favor of BS2. The HRR for discontinuation due to inefficacy and tolerability were 0.50 (95% CI: 0.37-0.67) and 0.20 (95% CI: 0.14-0.28), respectively, both favoring BS2. In adalimumab-naïve new starters also, better survival for the originator and BS2 were seen compared with BS1. In conclusion, adalimumab BS1 showed a significantly lower drug survival than BS2, primarily due to lower tolerability. These findings suggest that pharmaceutical differences can have an important impact on drug survival.