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The objective of this study was to investigate if the safety profile of upadacitinib was comparable to other DMARDs in treatment of patients with rheumatoid arthritis (RA). The study is a systematic literature review that includes articles from a search (date: 04/09/22) in the database Pubmed with the keywords: rheumatoid arthritis, upadacitinib and safety. The inclusion criteria: randomized controlled trials (RCT) and English articles. The search gave 17 articles of which three were excluded due to them not being RCTs. The study found that upadacitinib had a higher frequency of cases of side effects than that of placebo, methotrexate, adalimumab and abatacept. Treatment with upadacitinib had also higher risk of serious side effects and infections, herpes zoster, and CPK elevations. Higher doses of upadacitinib also gave a higher frequency of cases of side effects than that of lower doses of upadacitinib. However, upadacitinib did not differ in reported cases of death, malignancies, liver diseases or cardiovascular events from that of other treatments. In conclusion the study found that upadacitinib’s safety profile was comparable with those of placebo, methotrexate, abatacept and adalimumab. Although, upadacitinib had a higher frequency of side effects which, however, did not entail any major safety risk in comparison with other investigated treatments of RA.