What is the dose schedule of Upadacitinib (Rinvoq) in Crohn's disease and what is its efficacy in Ulcerative colitis?

Upadacitinib Dosing in Crohn's Disease and Efficacy in Ulcerative Colitis

Dose Schedule for Crohn's Disease

For Crohn's disease, use upadacitinib 45 mg once daily for induction (12 weeks), followed by either 15 mg or 30 mg once daily for maintenance therapy. 1, 2

Induction Phase

• 45 mg once daily for 12 weeks is the standard induction regimen 1
• Clinical remission rates of 44.4% versus 25.1% with placebo (p<0.001) 1
• Endoscopic response achieved in 40.2% versus 8.4% with placebo 1

Maintenance Phase

• After achieving clinical response at 12 weeks, transition to either 15 mg or 30 mg once daily 3
• At 52 weeks, clinical remission rates were 36.2% with 15 mg and 51.5% with 30 mg versus 15.2% with placebo 3
• Endoscopic response rates were 27.3% with 15 mg and 40.7% with 30 mg versus 7.2% with placebo 3
• The 30 mg maintenance dose demonstrates superior efficacy over 15 mg 3

Critical Dosing Consideration for Loss of Response

• If patients lose response after dose reduction to maintenance therapy, re-induction with 45 mg once daily is highly effective, recapturing clinical response in 80.4% of patients 4
• Among those who recaptured response, continuing 45 mg once daily for maintenance was superior to dose reduction (93.8% maintained remission on 45 mg versus 21.1% on 30 mg, p<0.001) 4
• This suggests that some patients may require ongoing 45 mg daily dosing rather than standard maintenance doses 4

Dose Adjustments for Special Populations

• Severe renal impairment (eGFR 15-30 mL/min/1.73m²): Use 30 mg once daily for induction and 15 mg once daily for maintenance 5
• Mild to moderate hepatic impairment (Child-Pugh A or B): Use 30 mg once daily for induction and 15 mg once daily for maintenance 5
• Severe hepatic impairment (Child-Pugh C): Not recommended 5
• End-stage renal disease: Not recommended 5

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Efficacy Data in Ulcerative Colitis

Upadacitinib demonstrates high-quality evidence for substantial efficacy in moderate to severe ulcerative colitis, with robust induction and maintenance outcomes. 6

Induction Efficacy (45 mg once daily for 8 weeks)

• Clinical remission rates: 26% (U-ACHIEVE) and 34% (U-ACCOMPLISH) versus 5% and 4% with placebo (p<0.0001) 7
• Adjusted treatment differences of 21.6% and 29.0% over placebo 7
• The British Society of Gastroenterology rates the overall certainty as HIGH for large benefit in induction of remission 6

Maintenance Efficacy (15 mg or 30 mg once daily for 52 weeks)

• Among patients who responded to induction, clinical remission at 52 weeks was achieved in:
  • 42% with 15 mg (adjusted difference 30.7% vs placebo, p<0.0001) 6, 7
  • 52% with 30 mg (adjusted difference 39.0% vs placebo, p<0.0001) 6, 7
  • 12% with placebo 7
• The 30 mg maintenance dose provides superior efficacy compared to 15 mg 6, 7

Real-World Experience

• In heavily pre-treated patients (100% prior anti-TNF exposure, 89.3% with ≥2 advanced therapies):
  • Clinical response: 76.0% at 4 weeks and 85.2% at 8 weeks 8
  • Clinical remission: 69.2% at 4 weeks and 81.5% at 8 weeks 8
  • Rapid onset with 36% achieving remission by week 2 8
• Among tofacitinib-exposed patients, 77.8% achieved clinical remission by 8 weeks, demonstrating efficacy even after JAK inhibitor failure 8

Guideline Recommendation

• The British Society of Gastroenterology recommends upadacitinib for induction and maintenance of remission in patients with moderate to severe ulcerative colitis 6
• The American Gastroenterological Association considers upadacitinib a "HIGHER efficacy medication" for ulcerative colitis 2
• Benefits extend to patients with previous biologic exposure 6

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Safety Considerations Across Both Indications

Mandatory Pre-Treatment Screening

• Screen for active and latent tuberculosis 1
• Evaluate for viral hepatitis 1
• Update immunizations 1
• Test for pregnancy 2

Laboratory Monitoring

• Interrupt treatment if absolute neutrophil count <1000 cells/mm³ 1
• Interrupt treatment if absolute lymphocyte count <500 cells/mm³ 1
• Check complete blood count with differential, liver enzymes at baseline and after initiation 2
• Check lipids at 12 weeks after initiation 2

High-Risk Populations Requiring Caution

The European Medicines Agency and FDA advise that JAK inhibitors should be used only if no suitable alternatives exist in: 6, 2

• Patients ≥65 years of age
• Current or long-term former smokers
• History of cardiovascular disease or risk factors for MACE
• History of venous thromboembolism
• Increased cancer risk

For these high-risk groups, use the lowest effective dose when possible 6

Common Adverse Events

• Acne/rosacea is the most common adverse event (22.9%-39% in real-world studies) 4, 8
• Herpes zoster occurred in 4.0-7.2% on maintenance therapy, mostly nonserious and single dermatome 1, 3
• Creatine phosphokinase elevation 7
• Nasopharyngitis 7

Serious Safety Signals

• Black box warnings for venous thromboembolism and major adverse cardiovascular events exist based on data from rheumatoid arthritis trials 1
• Gastrointestinal perforations reported rarely 1
• No deaths, active tuberculosis, lymphoma, or adjudicated MACE/VTE events in Crohn's disease trials through 52 weeks 3
• Events of cancer, MACE, or VTE reported infrequently in ulcerative colitis trials 7