Guidelines for Treating Crohn's Disease with Rinvoq (Upadacitinib)
Upadacitinib is conditionally recommended for induction and maintenance therapy in patients with moderate to severe Crohn's disease, particularly in those who have had an inadequate response or intolerance to anti-TNF therapy. 1
Indications and Positioning
- Upadacitinib (Rinvoq) is indicated for the treatment of adults with moderately to severely active Crohn's disease who have had an inadequate response or intolerance to one or more TNF blockers 2
- It is particularly valuable as it is the first oral agent shown to be effective and safe in both inducing and maintaining remission in Crohn's disease 1
- The European Crohn's and Colitis Organisation (ECCO) strongly recommends upadacitinib as induction therapy in moderate-to-severe Crohn's disease 3
Dosing Recommendations
Induction Phase
- The recommended dosage for induction is 45 mg once daily for 12 weeks 2
- Clinical response can be observed rapidly, with symptomatic improvement beginning within the first week of treatment 4
Maintenance Phase
- After induction, patients who respond should transition to maintenance therapy with either 15 mg or 30 mg once daily 2, 5
- The 30 mg dose demonstrated higher clinical remission rates (47.6%) compared to the 15 mg dose (37.3%) at week 52 5
Special Populations
- For patients with severe renal impairment (eGFR 15 to <30 mL/min/1.73m²):
- Induction: 30 mg once daily for 12 weeks
- Maintenance: 15 mg once daily 2
- For patients with mild to moderate hepatic impairment (Child-Pugh A or B):
- Induction: 30 mg once daily for 12 weeks
- Maintenance: 15 mg once daily 2
- Upadacitinib is not recommended for patients with severe hepatic impairment (Child-Pugh C) 2
Efficacy
- In phase 3 trials, significantly higher percentages of patients achieved clinical remission with upadacitinib 45 mg compared to placebo (49.5% vs 29.1% in U-EXCEL; 38.9% vs 21.1% in U-EXCEED) 5
- Endoscopic response rates were also significantly higher with upadacitinib 45 mg (45.5% vs 13.1% in U-EXCEL; 34.6% vs 3.5% in U-EXCEED) 5
- Real-world data from a French multicenter cohort study showed steroid-free clinical remission in 54% of patients with highly refractory Crohn's disease at week 12 6
- Upadacitinib has shown efficacy for perianal fistulizing Crohn's disease, with 44.7% of patients achieving resolution of drainage of perianal fistulas at the end of induction compared to 5.6% with placebo 7
Safety Considerations and Monitoring
Before initiating treatment:
- Update immunizations
- Screen for active and latent tuberculosis
- Evaluate for viral hepatitis
- Assess hepatic function
- Confirm pregnancy status 2
Monitor for:
Key safety concerns:
- Black box warnings for venous thromboembolism (VTE) and major adverse cardiovascular events (MACE) in higher-risk patients 1, 2
- Herpes zoster infections (reported in 4.0-7.2% of patients on maintenance therapy) 3, 5
- Hepatic disorders and neutropenia (more frequent with the 30 mg dose) 3, 5
- Acne/rosacea (reported in 11-39% of patients) 8, 6
- Gastrointestinal perforations (rare but reported in clinical trials) 3, 5
Treatment Considerations for Loss of Response
- For patients who lose response after transitioning to lower maintenance doses:
Limitations and Contraindications
Upadacitinib is not recommended for use in combination with:
- Other JAK inhibitors
- Biological therapies for Crohn's disease
- Potent immunosuppressants such as azathioprine and cyclosporine 2
Avoid initiation or interrupt treatment if:
- Absolute lymphocyte count is less than 500 cells/mm³
- Absolute neutrophil count is less than 1000 cells/mm³
- Hemoglobin level is less than 8 g/dL 2