What is the role of Rinvoq (upadacitinib) after pulmonary embolism (PE) for the treatment of ulcerative colitis?

From the Guidelines

Rinvoq (upadacitinib) can generally be resumed after a pulmonary embolism (PE) in patients with ulcerative colitis, but timing should be individualized based on risk assessment and anticoagulation status. Typically, Rinvoq should be held until the patient is stable on appropriate anticoagulation therapy, which usually takes 2-4 weeks after the PE event. When restarting, the standard dosing for ulcerative colitis is 45 mg once daily for induction (8 weeks), followed by 15 or 30 mg once daily for maintenance. Patients should be on concurrent anticoagulation therapy (such as apixaban, rivaroxaban, or warfarin at therapeutic doses) when Rinvoq is resumed. Close monitoring for both thrombotic and bleeding complications is essential. The decision to restart Rinvoq involves balancing the risk of recurrent thrombosis (JAK inhibitors may increase thrombosis risk) against the risk of ulcerative colitis flare. Patients with unprovoked PE or multiple risk factors may require longer anticoagulation before restarting. Consultation with both gastroenterology and hematology specialists is recommended to create an individualized treatment plan that addresses both the thrombotic risk and inflammatory bowel disease management, as suggested by the AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis 1.

Some key considerations include:

• The risk of thrombosis and related mortality is doubled in patients with UC compared to controls, and patients with IBD are at increased risk for venous thromboembolism (VTE) 1.
• The use of tofacitinib, another JAK inhibitor, has been associated with an increased risk of serious infections, mortality, malignancy, major cardiovascular events, and thrombosis, particularly at higher doses 1.
• The AGA clinical practice guidelines recommend using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment for the induction and maintenance of remission in adult outpatients with moderate-severe ulcerative colitis, with a strong recommendation and moderate quality evidence 1.

Given the potential risks and benefits, the decision to restart Rinvoq after a PE should be made on a case-by-case basis, taking into account the individual patient's risk factors, disease severity, and treatment history, as well as the latest clinical practice guidelines and evidence-based recommendations 1.

From the FDA Drug Label

THROMBOSIS Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Patients with symptoms of thrombosis should discontinue RINVOQ/RINVOQ LQ and be promptly evaluated

The use of Rinvoq after a pulmonary embolism (PE) for ulcerative colitis is not directly addressed in the provided drug label. However, given the increased risk of thrombosis associated with JAK inhibitors, including Rinvoq, caution should be exercised.

• Key consideration: Patients who have experienced a myocardial infarction or stroke should discontinue Rinvoq.
• Clinical decision: In the absence of direct guidance, it is prudent to avoid Rinvoq in patients at risk of thrombosis, including those who have recently experienced a pulmonary embolism. 2

From the Research

Rinvoq (Upadacitinib) after Proctosigmoidoscopy (PE) for Ulcerative Colitis

• Upadacitinib, also known as Rinvoq, is an oral, selective, and reversible JAK inhibitor that has demonstrated efficacy in patients with moderately to severely active ulcerative colitis 3, 4.
• The U-ACHIEVE Maintenance study showed that upadacitinib 15 mg and 30 mg once daily maintained clinical remission in a significantly higher proportion of patients compared to placebo 3.
• Another study found that upadacitinib demonstrated a positive efficacy and safety profile as induction and maintenance therapy for moderately to severely active ulcerative colitis 4.
• A systematic review of upadacitinib for acute severe ulcerative colitis found that most patients experienced rapid and sustained improvement, with a colectomy rate at 90 days of 16.3% 5.
• A network meta-analysis comparing the efficacy of pharmacologic interventions in ulcerative colitis found that upadacitinib had the highest likelihood of inducing clinical remission, clinical response, and endoscopic improvement, and also ranked highest in maintaining clinical remission and endoscopic improvement 6.

Key Findings

• Upadacitinib is effective in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis.
• Upadacitinib has a positive efficacy and safety profile as induction and maintenance therapy.
• Upadacitinib may be a safe and effective therapy for acute severe ulcerative colitis.
• Upadacitinib has a high likelihood of inducing and maintaining clinical remission, clinical response, and endoscopic improvement compared to other pharmacologic interventions.

Adverse Events

• The most commonly reported adverse events with upadacitinib include nasopharyngitis, creatine phosphokinase elevation, and acne 3, 4.
• Upadacitinib has been associated with a higher risk of herpes zoster, hepatic disorders, and neutropenia compared to placebo 3.
• Venous thromboembolic events have been reported with upadacitinib, but the risk is considered low 5.