These findings suggest that JAK inhibitors may not be the optimal choice as first-line therapy in biologic-naïve patients with rheumatoid arthritis. Instead, their use may be better reserved for selected patients who have demonstrated an inadequate response to conventional synthetic DMARDs or biologic DMARDs, a position that aligns with current treatment recommendations and the more cautious approach adopted following the findings of the Oral Surveillance study.

An interesting observation is that, unlike tofacitinib, baricitinib did not demonstrate a significant increase in cardiovascular events or malignancy risk in this analysis. Although indirect comparisons should be interpreted cautiously, this may represent a potentially important differentiating feature within the JAK inhibitor class.

Looking ahead, the forthcoming long-term safety data for upadacitinib will be of particular interest. It remains possible that its greater selectivity for JAK1 could translate into a more favorable safety profile, although this hypothesis will require confirmation through robust comparative and real-world evidence.