What are the risks of combining 45mg Rinvoq (upadacitinib) QD (once daily) and 35mg of Prednisone QD in a younger to middle-aged adult patient with acute ulcerative colitis and a history of moderate to severe disease?

Risks of Combining Rinvoq 45mg and Prednisone 35mg in Acute Ulcerative Colitis

Combining upadacitinib 45mg daily with prednisone 35mg daily carries significant infection risk, particularly serious infections, and the prednisone dose exceeds guideline-recommended maximum of 40mg daily, which increases adverse effects without additional benefit. 1

Corticosteroid Dose Concerns

The prednisone dose of 35mg daily is within acceptable range, but doses above 40mg provide no additional efficacy and increase adverse effects. 1

• Standard guideline-recommended dosing for moderate to severe ulcerative colitis is prednisolone 40mg daily, with no evidence of benefit from doses exceeding 40-60mg/day 1
• Approximately 50% of patients experience short-term corticosteroid-related adverse events including acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia 1
• The 35mg dose falls within the therapeutic range but approaches the upper limit where adverse effects increase without proportional benefit 1

Infection Risk with Combination Therapy

The combination of a JAK inhibitor with corticosteroids substantially increases infection risk, including serious and opportunistic infections. 2, 3

• Post-hoc analysis of upadacitinib trials demonstrated that patients receiving corticosteroids at baseline had higher rates of treatment-emergent adverse events, serious adverse events, and serious infections compared to those not receiving corticosteroids during induction 2
• In a multicenter study of 25 patients with acute severe UC treated with upadacitinib and intravenous corticosteroids, 1 patient (4%) experienced a venous thromboembolic event 3
• JAK inhibitors carry FDA warnings regarding cardiovascular risk, thrombotic events, and increased cancer risk, particularly in patients over 50 years old, smokers, or those with cardiovascular risk factors 1

Specific Safety Considerations for JAK Inhibitors

Upadacitinib requires careful monitoring for venous thromboembolism, major cardiovascular events, and malignancy, with risk amplified by concurrent corticosteroid use. 1

• JAK inhibitors should be used with caution in patients with risk factors for venous thromboembolism beyond those at highest risk (patients ≥65 years, history of atherosclerotic cardiovascular disease, current/long-term smokers, increased cancer risk) 1
• The combination may increase hyperlipidemia risk, requiring lipid monitoring 1
• Corticosteroid use at baseline was associated with higher adverse event rates during induction therapy with upadacitinib 2

Steroid-Sparing Benefit

Upadacitinib demonstrates effective steroid-sparing properties, allowing for corticosteroid withdrawal during maintenance therapy. 2

• In maintenance trials, patients receiving upadacitinib 30mg had lower rates of corticosteroid re-initiation (14%) compared to placebo (29%) 2
• Treatment-emergent adverse event rates normalized after corticosteroid withdrawal during maintenance therapy, suggesting the combination rather than upadacitinib alone drives increased infection risk 2
• Protocol-defined corticosteroid tapering should begin during maintenance weeks 0-8 to minimize cumulative exposure 2

Clinical Management Algorithm

Initiate combination therapy only if acute severe disease warrants both agents, with aggressive corticosteroid tapering once clinical response achieved. 2, 3

• Monitor closely for signs of infection, particularly during the first 8 weeks when both agents are combined 2
• Screen for latent tuberculosis and hepatitis B before initiating therapy 1
• Assess cardiovascular and thrombotic risk factors; consider alternative therapy if multiple risk factors present 1
• Implement protocol-driven corticosteroid taper starting at week 0-8 of maintenance to minimize infection risk 2
• Monitor absolute lymphocyte count, though no association between ALC <0.5 × 10⁹/L and infection events was observed in trials 4
• Consider therapeutic drug monitoring if inadequate response to optimize upadacitinib dosing 5

Duration of Combination Therapy

Limit concurrent corticosteroid use to the shortest duration necessary, ideally completing taper within 6-8 weeks. 1

• Standard corticosteroid courses should be tapered over 6-8 weeks 1
• Prolonging high-dose corticosteroids beyond 2 weeks without response should prompt treatment escalation or hospitalization 1
• Continued corticosteroid use beyond 7 days in hospitalized patients with acute severe UC refractory to intravenous steroids has not shown benefit 1