Extended Induction with Upadacitinib 45mg for Persistent Hematochezia
Continue upadacitinib 45mg daily for an additional 8 weeks (total 16 weeks of induction therapy) before considering this patient a treatment failure. 1, 2
Evidence for Extended Induction Strategy
Nearly half (48%) of patients who fail to respond to the initial 8-week induction regimen with upadacitinib 45mg respond to an additional 8 weeks of induction therapy, and more than half of these patients maintain clinical response at 1 year. 1 In the phase 3 trials, among 127 patients without clinical response at week 8,75 (59.1%) subsequently achieved clinical response after 16 weeks total of upadacitinib 45mg induction therapy. 2
This extended induction approach is supported by similar data with other JAK inhibitors—in the OCTAVE trial with tofacitinib 10mg twice daily, 52% of non-responders at week 8 achieved clinical response at week 16 after extended induction, with 56.1% maintaining clinical remission at 36 months. 1
Transition to Maintenance Therapy
After achieving clinical response with 16-week extended induction:
Re-randomize to maintenance dosing: Patients achieving clinical response at week 16 should transition to either upadacitinib 15mg or 30mg once daily for maintenance therapy. 2
Consider 30mg maintenance for severe disease: At week 52 of maintenance following extended induction, 43.6% of patients receiving upadacitinib 30mg achieved clinical remission versus 26.5% with 15mg. 2 The FDA label specifically states that 30mg once daily may be considered for patients with refractory, severe, or extensive disease. 3
Use lowest effective dose: Once response is achieved, use the lowest effective dosage needed to maintain response, but recognize that some patients with severe disease require the higher maintenance dose. 1, 3
Safety Monitoring During Extended Induction
Herpes zoster rates increase with longer duration (16 weeks) of exposure to upadacitinib 45mg during induction compared with 8 weeks. 2 Monitor carefully for:
- Herpes zoster infection (dose-dependent risk) 1, 2
- Serious infections 1, 4
- Venous thromboembolism, particularly in patients with risk factors 1
- Hepatic disorders and creatine phosphokinase elevation 5, 4
- Neutropenia and lymphopenia 5, 4
The British Society of Gastroenterology recommends using JAK inhibitors with caution in patients at increased risk of venous thromboembolism, cancer, or major cardiovascular problems. 1
When to Abandon Extended Induction
If the patient shows no clinical response after 16 weeks total of upadacitinib 45mg, switch to an alternative advanced therapy rather than continuing upadacitinib. 1 The AGA guidelines recommend infliximab, vedolizumab, risankizumab, or guselkumab as higher efficacy alternatives in this scenario. 1
Renal Function Considerations
For patients with severe renal impairment (eGFR 15 to <30 mL/min/1.73m²), reduce the extended induction dose to upadacitinib 30mg once daily. 3 No dosage adjustment is needed for mild or moderate renal impairment. 3