The Pharmacovigilance Risk Assessment Committee of the European Medicines Agency (PRAC EMA) has begun a safety review of Janus kinase (JAK) inhibitors used to treat several chronic inflammatory diseases (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, ulcerative colitis, and atopic dermatitis).
The review was triggered by the final results of a clinical trial (study A3921133) of the JAK inhibitor Xeljanz (tofacitinib). The results showed that patients who used Xeljanz for rheumatoid arthritis and who were at risk of cardiovascular disease more often had serious cardiovascular problems (for example, heart attack, stroke or death due to cardiovascular disease) and had a higher risk of developing cancer than when treated with medicinal products belonging to the class of TNF-alpha inhibitors. The studies also showed that, compared with TNF-alpha inhibitors, Xeljanz was associated with a higher risk of death from any cause, serious infections, and blood clots in the lungs and deep veins (venous thromboembolism, VTE).
In addition, preliminary results of an observational study involving another JAK inhibitor, Olumiant (baricitinib), also indicate an increased risk of serious cardiovascular problems and VTE in patients with rheumatoid arthritis treated with Olumiant, compared with those treated with TNF-alpha inhibitors.
Olumiant and other JAK inhibitors, when used to treat inflammatory disorders, act in the same way as Xeljanz. Therefore, PRAC will conduct a review to determine whether these risks are associated with all JAK inhibitors authorized in the EU for the treatment of inflammatory disorders and whether changes should be made to the marketing authorizations of these medicinal products.
Some measures to minimize these risks are already in place for the medicinal product Xeljanz as a result of the completion of the review in 2020, which analyzed interim results of study A3921133. In addition, the information on the medicinal product Xeljanz was further updated in 2021 to reflect the increased risk of serious cardiovascular and oncological problems observed after the publication of additional data from this study.
More about medicines
Janus kinase inhibitors are used to treat several chronic inflammatory diseases (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, ulcerative colitis and atopic dermatitis). The active substances in these medicinal products act by blocking the action of enzymes known as Janus kinases. These enzymes play an important role in the inflammation process that occurs in these disorders. By blocking the action of the enzymes, these medicinal products help reduce inflammation and other symptoms of these disorders.
Some JAK inhibitors (Jakavi and Inrebic) are used to treat myeloproliferative disorders; at this stage, the review will not include these medicinal products.
Learn more about the procedure
The review of JAK inhibitors in the treatment of inflammatory diseases was initiated at the request of the European Commission (EC) in accordance with Article 20 of Regulation (EC) No. 726/2004.
The review is conducted by the PRAC, which will draw up a set of recommendations. After that, the PRAC recommendations will be sent to the Committee for Medicinal Products for Human Use (CHMP), which will give the opinion of the European Medicines Agency. The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.
U.S. Food and Drug Administration (FDA)
On 1 September 2021, the U.S. Food and Drug Administration (FDA) announced an increased risk of serious cardiovascular disease, cancer, thrombosis and death with JAK inhibitors, based on a completed review of a large randomized clinical safety trial.
The FDA has required that information on the risks of serious cardiovascular diseases, cancer, blood clots and death be included in several sections of the package insert. The recommendations for healthcare professionals must include the need to consider the benefit/risk ratio for each individual patient. This applies especially to patients who smoke or have smoked in the past, those with other cardiovascular risk factors, those who have developed a malignant tumor, and those with a known malignant tumor, other than successfully treated non-melanoma skin cancer.
Healthcare professionals should advise patients on the benefits and risks of these medicinal products and recommend that they seek emergency medical care if they experience signs and symptoms of a heart attack, stroke, or blood clot.
List of medicinal products containing tofacitinib and upadacitinib and authorized for medical use in Ukraine (according to the State Register as of 10.02.2022). (11 KB) (Downloaded: 21.02.2022 08:33:45)
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