What are the most significant adverse events associated with the use of Rinvoq (upadacitinib)?

From the Guidelines

The most significant adverse events associated with Rinvoq (upadacitinib) include serious infections, malignancies, major cardiovascular events, thrombosis, and gastrointestinal perforations. These adverse events are a major concern due to Rinvoq's immunosuppressive effects, which can increase the risk of serious infections such as pneumonia, cellulitis, and herpes zoster, with higher doses increasing this risk 1. Malignancy risk, particularly lymphoma and non-melanoma skin cancers, is elevated, especially in patients with risk factors or prior malignancy, as noted in a recent study published in the British Journal of Dermatology 1. Cardiovascular adverse events include myocardial infarction and stroke, with higher risk in patients with existing cardiovascular disease. Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, has been reported, particularly in patients with thrombotic risk factors, and should be carefully evaluated in patients with a history of thromboembolic events 1. Some key points to consider when evaluating the risk of adverse events with Rinvoq include:

• Serious infections: higher doses increase the risk, and patients with risk factors such as age or comorbidities are more susceptible 1
• Malignancy: risk is elevated, especially in patients with risk factors or prior malignancy, and should be carefully evaluated 1
• Cardiovascular events: higher risk in patients with existing cardiovascular disease, and venous thromboembolism should be carefully evaluated in patients with thrombotic risk factors 1
• Gastrointestinal perforations: though rare, can occur, especially in patients with diverticulitis or taking concomitant medications like NSAIDs or corticosteroids
• Laboratory abnormalities: common, including neutropenia, lymphopenia, anemia, elevated liver enzymes, and lipid elevations, and should be monitored regularly. These risks stem from Rinvoq's mechanism as a JAK inhibitor, which modulates multiple cytokine pathways involved in immune function, inflammation, and cellular processes.

From the FDA Drug Label

Serious Infections Inform patients that they may be more likely to develop infections when taking RINVOQ/RINVOQ LQ Malignancies Inform patients that RINVOQ/RINVOQ LQ may increase their risk of certain cancers Major Adverse Cardiovascular Events Inform patients that RINVOQ/RINVOQ LQ may increase their risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, and cardiovascular death Thrombosis Inform patients that events of deep venous thrombosis and pulmonary embolism have been reported in clinical trials with RINVOQ. Hypersensitivity Reactions Advise patients to discontinue RINVOQ/RINVOQ LQ and seek immediate medical attention if they develop any signs and symptoms of allergic reactions Gastrointestinal Perforations Inform patients that gastrointestinal perforations have been reported in clinical trials with RINVOQ Retinal Detachment Inform patients that retinal detachment has been reported in clinical trials with RINVOQ

The most significant adverse events associated with the use of Rinvoq (upadacitinib) include:

• Serious Infections: increased risk of developing infections
• Malignancies: increased risk of certain cancers
• Major Adverse Cardiovascular Events: increased risk of myocardial infarction, stroke, and cardiovascular death
• Thrombosis: events of deep venous thrombosis and pulmonary embolism
• Hypersensitivity Reactions: allergic reactions
• Gastrointestinal Perforations: perforations have been reported in clinical trials
• Retinal Detachment: retinal detachment has been reported in clinical trials 2 2

From the Research

Adverse Events Associated with Rinvoq (Upadacitinib)

The most significant adverse events associated with the use of Rinvoq (upadacitinib) are:

• Upper respiratory tract infection
• Nasopharyngitis
• Urinary tract infection
• Creatine phosphokinase elevation
• Acne
• Herpes zoster
• Opportunistic infections (excluding tuberculosis, herpes zoster, and oral candidiasis)
• Serious infection
• Anemia
• Malignancies
• Adjudicated major adverse cardiovascular events (MACEs)
• Venous thromboembolic events (VTEs)
• Deaths

Specific Adverse Events by Condition

The adverse events associated with upadacitinib vary by condition:

• In patients with ulcerative colitis, the most commonly reported adverse events were nasopharyngitis, creatine phosphokinase elevation, and acne 3
• In patients with rheumatoid arthritis, the most commonly reported adverse events were upper respiratory tract infection, nasopharyngitis, and urinary tract infection 4, 5
• In patients with psoriatic arthritis, the most commonly reported adverse events were upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase 6

Comparison with Other Treatments

Studies have compared the safety profile of upadacitinib with other treatments, including:

• Adalimumab: upadacitinib had a similar safety profile to adalimumab, with the exception of higher rates of herpes zoster and opportunistic infections 4, 6
• Methotrexate: upadacitinib had a higher rate of serious infections and creatine phosphokinase elevations compared to methotrexate 4
• Placebo: upadacitinib had a higher rate of adverse events, including serious infections and malignancies, compared to placebo 3, 5