A systematic review reviewed 87 clinical trials from 2014–2025 of JAK inhibitors in the treatment of rheumatoid arthritis according to PRISMA, ACR/EULAR 2010 criteria. Most studies were from China (42) and the USA (32), with the USA leading the way in R&D with a mix of independent and collaborative projects. Studies targeting JAK2/JAK3 increased from 25% (2014–2018) to 62.7% (2019–2025, p < 0.01), with a shift to multitarget combinations such as TYK2 + JAK1 and a shift away from pan-JAK inhibitors. JAK inhibitors have demonstrated molecular target-dependent efficacy, with infections being the most common adverse events with serious adverse event rates of 2.91–7.37% and specific safety profiles. Data disclosure has been patchy, with gaps in phase IV and drug data. JAK inhibitors represent key therapies against rheumatoid arthritis with varying efficacy and safety by target. Future studies should focus on phase IVs, regional subgroups, head-to-head comparisons, and standardized disclosures. Review registration: CRD420261290714.