Rinvoq (Upadacitinib) for Moderate to Severe Crohn's Disease
Rinvoq (upadacitinib) is recommended as an effective treatment option for adults with moderately to severely active Crohn's disease who have had an inadequate response or intolerance to one or more TNF blockers. 1
Indication and Efficacy
- Rinvoq is FDA-approved 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 1
- In phase 3 clinical trials (U-EXCEL and U-EXCEED), upadacitinib 45mg once daily for induction demonstrated significantly higher clinical remission rates compared to placebo (49.5% vs 29.1% in U-EXCEL; 38.9% vs 21.1% in U-EXCEED) 2
- Endoscopic response rates were also significantly higher with upadacitinib compared to placebo (45.5% vs 13.1% in U-EXCEL; 34.6% vs 3.5% in U-EXCEED) 2
- Maintenance therapy with either 15mg or 30mg once daily maintained clinical remission and endoscopic response at 52 weeks at significantly higher rates than placebo 2
Positioning in Treatment Algorithm
- According to AGA guidelines, upadacitinib should be considered after failure of TNF-alpha inhibitors 3
- For patients with primary non-response to TNF inhibitors, the AGA recommends ustekinumab and suggests vedolizumab, but upadacitinib now provides an additional option with a novel mechanism of action 3
- Upadacitinib is the first JAK inhibitor approved for Crohn's disease and provides the first advanced oral treatment option for patients with moderate to severe CD 4
- Upadacitinib should not be used in combination with other JAK inhibitors, biological therapies for Crohn's disease, or with potent immunosuppressants such as azathioprine and cyclosporine 1
Dosing
- For induction in Crohn's disease: 45mg once daily for 12 weeks 2
- For maintenance: 15mg or 30mg once daily 2
- Patients should be evaluated for response during the induction period to determine need for continued therapy 2
Special Considerations and Safety
- Before initiating treatment, patients should be evaluated for active and latent tuberculosis, viral hepatitis, hepatic function, and pregnancy status 1
- Avoid initiation or interrupt therapy if absolute lymphocyte count is less than 500 cells/mm³, absolute neutrophil count is less than 1000 cells/mm³, or hemoglobin level is less than 8 g/dL 1
- Safety concerns include:
- Increased risk of serious infections 1, 2
- Herpes zoster infections (more frequent with higher doses) 2
- Hepatic disorders and neutropenia (more common with 30mg dose) 2
- Gastrointestinal perforations (reported in clinical trials) 2
- Potential cardiovascular risks (based on data from other JAK inhibitors) 1
Efficacy in Special Populations
- Upadacitinib has shown efficacy in patients with fistulizing Crohn's disease, particularly perianal fistulas 5
- In a post-hoc analysis of phase 3 trials, upadacitinib demonstrated higher rates of fistula drainage resolution and closure of external openings compared to placebo 5
- Real-world data from a tertiary center showed subjective and objective responses in 25% and 42% of medically refractory CD patients, respectively, even at doses lower than those being studied for CD 6
Limitations and Future Directions
- Long-term safety data specific to Crohn's disease patients is still being collected 4
- Head-to-head comparisons with other biologics for Crohn's disease are lacking 3, 4
- The optimal positioning of upadacitinib in treatment algorithms relative to other biologics requires further research 4
- Patient-specific predictors of response to upadacitinib versus other therapies are needed to guide personalized treatment decisions 3