Can prednisolone be added to upadacitinib (Rinvoq) during an ulcerative colitis flare?

Yes, prednisolone can be added to upadacitinib (Rinvoq) during an ulcerative colitis flare

Adding prednisolone to upadacitinib during an acute flare is a clinically appropriate and evidence-supported approach for managing ulcerative colitis exacerbations, including acute severe ulcerative colitis (ASUC).

Clinical Evidence Supporting Combination Therapy

The combination of corticosteroids with upadacitinib has demonstrated effectiveness in real-world practice. In a multicenter study of 25 patients with ASUC treated with upadacitinib plus intravenous corticosteroids, 76% (19/25) avoided colectomy at 90 days, and 83% of those who avoided surgery achieved steroid-free clinical remission 1. A systematic review of 55 ASUC patients treated with upadacitinib showed a colectomy rate of only 16.3% at 90 days, with 80% achieving steroid-free remission among those who avoided surgery 2.

Guideline-Based Approach

The 2025 British Society of Gastroenterology guidelines explicitly support this strategy 3:

• Prednisolone (40 mg/day) is recommended for moderate-to-severe UC flares, with evidence showing superiority over lower doses (20 mg/day) and no additional benefit above 40-60 mg/day
• Advanced therapies like upadacitinib should be initiated if there is inadequate response to oral corticosteroids within 2 weeks, or to avoid repeated corticosteroid courses
• The guidelines emphasize that corticosteroids can be combined with advanced therapies during induction, though they should not be used for long-term maintenance

Safety Considerations from FDA Label

The Rinvoq FDA label does not prohibit corticosteroid use 4. However, it states that upadacitinib is "not recommended for use in combination with...potent immunosuppressants such as azathioprine and cyclosporine"—notably, corticosteroids are not listed in this restriction.

Post-hoc analysis of Phase 3 trials showed that 38% of patients were receiving corticosteroids at baseline when starting upadacitinib 5. Importantly:

• Upadacitinib achieved similar clinical remission rates regardless of baseline corticosteroid use
• Patients on corticosteroids at baseline had higher adverse event rates during induction, but rates normalized after corticosteroid withdrawal during maintenance
• Upadacitinib demonstrated effective steroid-sparing properties, with fewer patients requiring corticosteroid re-initiation compared to placebo

Practical Implementation

During an acute flare:

1. Start prednisolone 40 mg/day (oral) for moderate-to-severe flares 3
2. Continue upadacitinib at current maintenance dose (15 or 30 mg daily), or initiate at induction dose (45 mg daily) if starting therapy
3. Assess response within 2 weeks
4. Taper prednisolone according to protocol once clinical improvement occurs (typically over 8-12 weeks)
5. Maintain upadacitinib as long-term therapy—do not use corticosteroids for maintenance 3

Important Caveats

• Monitor for increased infection risk: The combination increases immunosuppression, particularly during the induction phase when both drugs are at therapeutic levels 5
• Thrombosis risk: JAK inhibitors carry thrombotic risk; avoid in patients with pre-existing thrombotic risk factors, especially when combined with corticosteroids 4
• Herpes zoster: Consider prophylaxis given increased risk with JAK inhibitors
• Duration matters: This is a bridge strategy—the goal is steroid-free remission maintained by upadacitinib alone

The evidence strongly supports that this combination is both effective and commonly used in clinical practice, with the corticosteroid serving as a bridge therapy during acute exacerbations while upadacitinib provides the definitive disease control 1, 5, 2.