What should be done for an adult patient with a history of ulcerative colitis, currently taking 45mg of Rinvoq (upadacitinib) daily, who is experiencing nosebleeds?

Management of Nosebleeds in a Patient on Rinvoq 45mg Daily

Do not discontinue Rinvoq solely due to nosebleeds unless they are severe, recurrent, or associated with other bleeding manifestations; instead, evaluate for underlying causes and consider dose reduction to 30mg daily for maintenance therapy if the patient is beyond the 8-week induction phase. 1

Immediate Assessment Required

• Check complete blood count to rule out thrombocytopenia or anemia from bleeding, as JAK inhibitors can cause neutropenia and other hematologic abnormalities 1
• Assess bleeding severity: Document frequency, duration, volume of blood loss, and whether bleeding is unilateral or bilateral
• Evaluate for venous thromboembolism risk factors, as JAK inhibitors carry warnings for thrombotic events, though nosebleeds themselves are not a typical manifestation 1
• Screen for concurrent anticoagulant or antiplatelet use that may compound bleeding risk
• Examine nasal mucosa for local causes (trauma, dryness, infection, structural abnormalities)

Treatment Phase Considerations

If Patient is in 8-Week Induction Phase (45mg daily)

• Continue 45mg daily if nosebleeds are mild and self-limiting, as this is the established induction dose with proven efficacy (26-34% clinical remission at week 8) 2, 3
• Implement local measures: Saline nasal spray, humidification, petroleum jelly to nasal vestibule, avoid nasal trauma
• Monitor closely for worsening bleeding or development of other hemorrhagic manifestations

If Patient is Beyond Induction (Week 8+)

• Transition to maintenance dosing of 30mg daily, as this is the recommended maintenance dose with superior efficacy (53.6% clinical remission at week 52) compared to 15mg (40.4%) 4
• The 45mg dose is specifically indicated for induction only, not long-term maintenance 2, 4
• Do not continue 45mg beyond 16 weeks maximum, even in cases of modest response, due to increased safety concerns at higher doses 1

Safety Monitoring Algorithm

Red Flags Requiring Immediate Action

• Severe or recurrent nosebleeds requiring medical intervention (cauterization, packing)
• Development of other bleeding manifestations (hematuria, gastrointestinal bleeding, easy bruising)
• Thrombocytopenia (platelet count <100,000/μL)
• Signs of venous thromboembolism (leg swelling, chest pain, dyspnea) - paradoxically, JAK inhibitors increase VTE risk despite bleeding 1

If Red Flags Present

• Discontinue upadacitinib immediately
• Switch to alternative advanced therapy: infliximab (RR 2.85 for induction), vedolizumab (RR 2.22), or ustekinumab (RR 2.91) 1
• These biologics have different safety profiles without the same thrombotic or bleeding concerns

Risk Stratification Context

• JAK inhibitors should be used with caution in patients with risk factors for cardiovascular events, thromboembolism, or cancer 1
• The British Society of Gastroenterology specifically recommends dose reduction in patient groups at risk of VTE, cancer, or major cardiovascular problems where possible 1
• Nosebleeds are not a commonly reported adverse event in the phase 3 trials (U-ACHIEVE, U-ACCOMPLISH), where the most common adverse events were nasopharyngitis, acne, and CPK elevation 2, 4

Practical Management Steps

1. Complete hematologic workup within 48 hours
2. If CBC normal and nosebleeds mild: Continue current dose with local nasal care measures
3. If beyond week 8: Reduce to 30mg daily maintenance dose regardless of nosebleed severity 4
4. If nosebleeds persist or worsen on 30mg: Switch to biologic therapy (infliximab preferred as first-line alternative) 1
5. Document all bleeding episodes and reassess at 2-week intervals during dose adjustment

Common Pitfall to Avoid

Do not empirically discontinue effective therapy for minor mucosal bleeding without proper evaluation - nosebleeds may be unrelated to upadacitinib and due to environmental factors, local trauma, or concurrent medications. However, maintain heightened vigilance given the known hematologic effects of JAK inhibitors 1, 2.