Global safety report: more VTE events on JAK inhibition in rheumatoid arthritis

A register study explored worldwide data on MACEs and venous thromboembolism associated with JAK inhibitors compared to anti-TNF agents in RA.

From 16 million declared cases, 50,694 were RA patients on JAK inhibitors and 239,914 received anti-TNFs

To further elucidate recently emerged concerns about cardiovascular and thromboembolic risks due to JAK inhibitors versus anti-TNF drugs, the presented French study analysed data from The World Health Organization Global Individual Case Safety Report database  (VigiBase®)1. In this worldwide database, case reports can be submitted by physicians and non-physicians.

Prerequisites for case selection were patients with RA aged 18–75 years, who had adverse events related to JAK inhibitors or anti-TNF medication.  MACEs, i.e. myocardial infarction, stroke and cardiovascular death, as well as VTE in terms of pulmonary embolism and deep vein thrombosis were classified as events of interest. Out of 16 million declared cases between 2011 and 2022, 50,694 were RA patients on JAK inhibitors and 239,914 received anti-TNFs.

The analysis revealed MACEs in 817 JAK inhibitor-treated patients and 3,379 patients treated with anti-TNF, with 23% and 33% registered by physicians, respectively. As for VTE, reports were found in 596 and 818 cases, in patients treated with JAK inhibitors and anti-TNFs, respectively, with 46% and 38% entering the database upon physician notification. Overall, most patients were 60 years of age or older.

No increase in events with JAK inhibition

In the disproportionality analysis of MACEs in the entire population, the study found no increase in events with JAK inhibition. “However, after stratification on the source of reporting, meaning physician versus non-physician, we could observe a slight increase of reported MACEs with JAK inhibition in comparison to anti-TNF, as well as an increase of myocardial infarction,” Prof. Adeline Ruyssen-Witrand (University Hospital of Toulouse III Paul Sabatier, France) told. This was significantly indicated by adjusted reporting odds ratios (ROR) of 1.45 (MACEs) and 1.70 (myocardial infarction) in the physician-reported subgroups.

With regard to VTE, there was an increased likelihood in the main analysis (ROR 3.48), and also after stratification according to physician (ROR 8.51) and non-physician reports (ROR 1.96). At further stratification according to the date of declaration in VigiBase®, there was an increase after the authority alerts. However, Prof. Ruyssen-Witrand underlined that in the year prior to these alerts, the study results already revealed an increase in risk for the 2 events with JAK inhibitors in comparison to anti-TNFs, with an odds ratio of 1.24 for MACEs and 1.84 for VTE.

She concluded that this kind of analysis can be very useful for clinicians to detect early safety signals after a new drug marketing use, especially when focusing on physician-declared cases.

1. Ruyssen-Witrand A, et al. Comparison of major cardiovascular and thromboembolic events in safety reports between rheumatoid arthritis patients treated with JAK-inhibitors versus anti-TNF: results from VigiBase®. OP0268, EULAR 2022, 1-4 June, Copenhagen, Denmark.