Table 1.

Summary of actions taken by key international regulatory bodies regarding JAKi use

Jurisdiction	Regulatory body	Date	Relevant JAKi	Action
United States	Food and Drug Administration	February 2021 [16]	Tofacitinib, baricitinib, upadacitinib	Boxed warning for MACE, malignancy, and mortality with recommendation for the use of JAKi in moderately to severely active RA with an inadequate response or intolerance to TNF blockers
European Union	European Medicines Agency	March 2023 [18]	Tofacitinib, baricitinib, upadacitinib, filgotinib, abrocitinib	Recommendation for the use of JAKi across all approved indications in inflammatory and dermatologic diseases only if no suitable alternative treatments available for patients with the following risk factors:
				Age ≥ 65
				Increased risk of cardiovascular disease
				Current or past long-time smoking
				Increased risk of cancer
United Kingdom	Medicines and Healthcare products Regulatory Agency	April 2023 [148]	Tofacitinib, baricitinib, upadacitinib, filgotinib, abrocitinib	Recommendation for the use of JAKi only if no suitable alternative treatments available for patients with the following risk factors:
				Age ≥ 65
				Current or past long-time smoking
				Other risk factors for cardiovascular disease or malignancy
Canada	Health Canada	October 2022 [157]	Tofacitinib, baricitinib, upadacitinib, filgotinib, abrocitinib	Recommendation to consider the benefits and risks of JAKi for the individual patient, particularly for patients with the following risk factors:
				Above 65 years of age
				Current or past smokers
				Other cardiovascular or malignancy risk factors
				Underlying malignancy or those who develop a malignancy
				Increased risk of thrombosis
Australia	Therapeutic Goods Administration	May 2023 [158]	Tofacitinib, baricitinib, upadacitinib	Boxed warning and recommendation for the use of JAKi only if no suitable treatment alternatives are available for patients with the following risk factors:
				History of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers)
				Malignancy risk factors (such as currently malignancy or history of malignancy)
				Age ≥ 65

JAKi JAK (Janus kinase) inhibitors, MACE major adverse cardiovascular events, RA rheumatoid arthritis