New Boxed Warnings for JAK Inhibitors

The Therapeutic Goods Administration (TGA) has published a Medicines Safety Update for the Janus kinase (JAK) inhibitors, tofacitinib, baricitinib and upadacitinib. This update relates to the findings of the ORAL Surveillance study, a large, post-authorisation, safety end-point trial of patients with active rheumatoid arthritis taking tofacitinib or a tumour necrosis factor (TNF) inhibitor. As baricitinib and upadacitinib have a similar mechanism of action to tofacitinib, the TGA considers that the findings of this study are also relevant to these agents.

To be enrolled in the ORAL Surveillance study, participants had to be 50 years of age or older with at least one cardiovascular risk factor. During a median follow-up of four years, the incidence of major adverse cardiovascular events was 3.4% in patients taking tofacitinib, compared to 2.5% for those treated with a TNF inhibitor. The incidence of cancers (excluding nonmelanoma skin cancer) was 4.2% in the tofacitinib group and 2.9% in the TNF inhibitor group. Subgroup analyses found that these differences were more pronounced in patients 65 years of age or older. The incidence of thromboembolic events, serious infections, and death due to any cause was also higher for tofacitinib compared to TNF inhibitors.

The TGA recommends periodic skin examinations and regular re-evaluation of thrombosis risk for patients taking tofacitinib, baricitinib, or upadacitinib. A new boxed warning has also been added to the product information documents for these medicines advising consideration of alternative therapies for patients who are 65 years of age or older or have cardiovascular or malignancy risk factors.