The European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has started a review of the safety of Janus kinase (JAK) inhibitors used to treat several chronic inflammatory disorders (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, ulcerative colitis and atopic dermatitis).
The review was prompted by the final results from a clinical trial (study A3921133) of the JAK inhibitor Xeljanz (tofacitinib). The results showed that patients taking Xeljanz for rheumatoid arthritis and who were at risk of heart disease were more likely to experience a major cardiovascular problem (such as heart attack, stroke or death due to cardiovascular disease) and had a higher risk of developing cancer than those treated with medicines belonging to the class of TNF-alpha inhibitors. The study also showed that compared with TNF-alpha inhibitors, Xeljanz was associated with a higher risk of death due to any cause, serious infections and blood clots in the lungs and in deep veins (venous thromboembolism VTE).
In addition, preliminary findings from an observational study involving another JAK inhibitor, Olumiant (baricitinib), also suggest an increased risk of major cardiovascular problems and VTE in patients with rheumatoid arthritis treated with Olumiant compared with those treated with TNF-alpha inhibitors.
In the treatment of inflammatory disorders, Olumiant and other JAK inhibitors work in a similar way to Xeljanz. PRAC will therefore carry out a review to determine whether these risks are associated with all JAK inhibitors authorised in the EU for the treatment of inflammatory disorders and whether the marketing authorisations for these medicines should be amended.
Some measures to minimise these risks are already in place for Xeljanz as a result of a review finalised in 2020, which analysed the interim results of study A3921133. In addition, the product information for Xeljanz was further updated in 2021 to reflect the increased risk of major cardiovascular problems and cancer observed after the release of additional data from this study.
Please refer to the following website in EMA for details:
http://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-7-10-february-2022
In Hong Kong, there are 3 registered pharmaceutical products containing tofacitinib, namely Xeljanz Tablets 5mg (HK-63303), Xeljanz XR Extended Release Tablets 11mg (HK-66141) and Xeljanz Tablets 10mg (HK-66833) which are registered by Pfizer Corporation Hong Kong Limited; and 2 products containing baricitinib, namely Olumiant Tablets 2mg (HK-65663) and Olumiant Tablets 4mg (HK-65664) which are registered by Eli Lilly Asia, Inc. All products are prescription-only medicines.
So far, the Department of Health (DH) has received 8 cases of adverse drug reaction related to tofacitinib, of which one case was related to lung cancer, 3 cases were related to deep vein thrombosis, one case was related to pneumonia, one case was related to herpes zoster disseminated, one case was related to cellulitis and one case was related to disseminated tuberculosis. The DH has received 3 cases of adverse drug reaction related to baricitinib, of which one case was related to deep vein thrombosis.
Related news on the risk of blood clots and death of tofacitinib was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 26 Feb 2019, with the latest update posted on 13 Jan 2022. Letters to inform local healthcare professionals were issued by the DH on 29 Jul 2019 and 19 Jun 2020. In Dec 2019, the Registration Committee of the Pharmacy and Poisons Board discussed the matter, and decided that the sales pack or package insert of tofacitinib products should include safety information about increased risk of blood clots and death with higher dose (10 mg twice daily).
Related news on the risk of serious heart-related problems and cancer of tofacitinib was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 5 Feb 2021, with the latest update posted on 13 Jan 2022. Letters to inform local healthcare professionals were issued by the DH on 15 Jun 2021. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Related news on the risk of blood clots of baricitinib was previously issued by the United Kingdom Medicines and Healthcare products Regulatory Agency and Health Canada, and was posted on the Drug Office website on 19 Mar 2020 and 19 Jun 2020 respectively. The current local product inserts already contain safety information on the risk of venous thromboembolism.
As the review is ongoing, the DH will remain vigilant on its final conclusions and recommendations, and safety update issued by overseas drug regulatory authorities for consideration of any action deemed necessary.
Ends/ Saturday, Feb 12, 2022
Issued at HKT 12:00
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