TOPIC: Janus Kinase (JAK) Inhibitors: Drug Safety Communication - FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death (1)
AUDIENCE: Patient, Rheumatology, Gastroenterology, Cardiology, Neurology, Oncology, Pharmacy, Health Professional
ISSUE: The FDA is requiring revisions to the Boxed Warning, FDA's most prominent warning, for Xeljanz/Xeljanz XR (tofacitinib), Olumiant (baricitinib) and Rinvoq (upadacitinib) to include information about the risks of serious heart-related events, cancer, blood clots, and death.
Based on the review of a large randomized safety clinical trial, the FDA has concluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR. This trial compared Xeljanz with another type of medicine used to treat arthritis called tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis. The trial's final results also showed an increased risk of blood clots and death with the lower dose of Xeljanz.
The FDA is requiring new and updated warnings for two other arthritis medicines in the same drug class as Xeljanz, called JAK inhibitors, Olumiant and Rinvoq. Olumiant and Rinvoq have not been studied in trials similar to the large safety clinical trial with Xeljanz, so the risks have not been adequately evaluated. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial.
Two other JAK inhibitors, Jakafi (ruxolitinib) and Inrebic (fedratinib), are not indicated for the treatment of arthritis and other inflammatory conditions and so are not a part of the updates being required to the prescribing information for Xeljanz, Xeljanz XR, Olumiant, and Rinvoq. If FDA becomes aware of any additional safety information or data that warrants updates to the prescribing information for these medicines, the FDA may take further action and will alert the public.
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BACKGROUND: Xeljanz/Xeljanz XR, Olumiant, and Rinvoq are used to treat certain serious, chronic, and progressive inflammatory conditions. All three medicines are approved to be used alone or with other drugs to treat rheumatoid arthritis, a condition in which the body attacks its own joints, causing pain, swelling, joint damage, and loss of function. Xeljanz is also approved to treat psoriatic arthritis, a condition that causes joint pain and swelling; ulcerative colitis, which is a chronic, inflammatory disease affecting the colon; and polyarticular course juvenile idiopathic arthritis, a type of childhood arthritis.
美國FDA要求廠商修訂Xeljanz/Xeljanz XR (tofacitinib)、Olumiant (baricitinib)和Rinvoq (upadacitinib)的加框警語，內容需包含有關嚴重心臟相關事件、癌症、血栓和死亡的風險。
美國FDA基於一大型隨機安全性相關之臨床試驗的審查，該試驗於類風濕性關節炎患者中，將Xeljanz與另一種用於治療關節炎患者的藥物：腫瘤壞死因子(TNF)抑制劑進行比較，結果顯示Xeljanz 和 Xeljanz XR會增加嚴重心臟相關事件(例如心臟病發作或中風)、癌症、血栓和死亡的風險。且較低劑量的Xeljanz 亦會增加血栓和死亡的風險。
美國FDA亦要求與Xeljanz同屬於JAK抑制劑的另外兩種關節炎相關藥物，Olumiant和Rinvoq更新藥物安全警訊。 Xeljanz/Xeljanz XR、Olumiant和Rinvoq皆被核准單獨使用或與其他藥品合併用於治療類風濕性關節炎；Xeljanz尚被核准用於治療乾癬性關節炎、潰瘍性結腸炎和多關節幼年特發性關節炎。Olumiant和Rinvoq尚未在類似於 Xeljanz的大型安全性臨床試驗中進行研究，因此尚未充分評估風險。然而由於它們與Xeljanz具有相同的作用機轉，因此美國FDA認為這類藥物可能具有與Xeljanz安全性試驗中相似的風險。另有兩種JAK抑制劑：Jakafi（ruxolitinib）和Inrebic（fedratinib）不適用於治療關節炎和其他發炎性疾病，因此不需要如同Xeljanz、Xeljanz XR、Olumiant和 Rinvoq一樣更新仿單，增加此風險訊息。如果美國FDA發現任何額外的安全警訊或數據需更新這類藥品之仿單，會再採取進一步處置並提醒大眾。