Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis

Serious Infections

Patients treated with LISRAYA are at increased risk of developing serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death. 

Reported infections with use of Janus kinase (JAK) inhibitors, including LISRAYA: 

• Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Evaluate and test patients for latent and active TB infection prior to and during LISRAYA treatment. If positive, treat for TB. Monitor all patients for active TB during treatmentincluding patients who tested negative of a latent TB infection prior to LISRAYA treatment. 
• Invasive fungal infections. Patients with invasive fungal infections may present with disseminated, rather than localized, disease. 
• Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens. 

Avoid use of LISRAYA in patients with an active, serious infection, including localized infections. Consider the risks and benefits of LISRAYA in patients with chronic or recurrent infection prior to initiating treatment. Closely monitor patients for signs and symptoms of infection during and after treatment with LISRAYA. If a serious infection occurs, interrupt LISRAYA treatment until the infection resolves or is adequately treated [see Warnings and Precautions (5.1)]. 

Mortality

A higher rate of all-cause mortality, including sudden cardiovascular death was observed with another Janus kinase (JAK) inhibitor when compared to tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis (RA) [see Warnings and Precautions (5.2)]. LISRAYA is not approved for use in patients with RA. 

Malignancy

Malignancies have occurred in patients treated with LISRAYA. A higher rate of malignancies (excluding non-melanoma skin cancer), lymphomas, and lung cancers was observed with another JAK inhibitor when compared to TNF blockers in patients with RA . LISRAYA is not approved for use in patients with RA. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions (5.3)]. 

Major Adverse Cardiovascular Events

Major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) have occurred in patients treated with LISRAYA. A higher rate of MACE was observed with another JAK inhibitor when compared to TNF blockers in patients with RA. LISRAYA is not approved for use in patients with RA. Patients who are current or past smokers are at additional increased risk. Discontinue LISRAYA in patients who have experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4)].

Thrombosis

Thromboses, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated for inflammatory conditions with JAK inhibitors, including LISRAYA. Many of these adverse reactions were serious and some resulted in death. A higher rate of thromboses was observed with another JAK inhibitor when compared to TNF blockers in patients with RA. LISRAYA is not approved for use in patients with RA. Avoid LISRAYA in patients who may be at risk of thrombosis. If symptoms of thrombosis occur, discontinue LISRAYA, promptly evaluate, and appropriately treat [see Warnings and Precautions (5.5)].