What is the recommended dosing regimen for ozanimod (siponimod) in patients with moderate to severe active ulcerative colitis?

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Ozanimod Dosing Regimen for Moderate to Severe Active Ulcerative Colitis

Ozanimod requires a 7-day dose titration regimen followed by maintenance dosing at 0.92 mg once daily, regardless of whether it is being used for induction or maintenance therapy. 1

Dosing Schedule

Initial Titration (Days 1-7)

  • A mandatory 7-day dose titration is required when initiating ozanimod, whether starting as induction therapy or transitioning for maintenance after another advanced therapy 1
  • This titration regimen is critical for minimizing cardiac effects, particularly bradycardia and atrioventricular conduction delays 2

Maintenance Dosing

  • After completing the 7-day titration, continue with ozanimod 0.92 mg once daily for both induction and maintenance phases 1, 2
  • The same 0.92 mg daily dose is used throughout treatment without dose adjustments based on disease phase 1, 2

Treatment Duration and Response Timeline

Induction Phase

  • Clinical efficacy is assessed at Week 10 following initiation 2, 3
  • Clinical remission rates at Week 10 were 18% with ozanimod versus 6% with placebo in the True North trial 2
  • Biologic-naive patients demonstrate superior response rates (23% clinical remission) compared to those with prior biologic exposure (17.2% with 1 prior biologic, 3.7% with 2+ prior biologics) 4

Maintenance Phase

  • Patients who respond to induction continue the same 0.92 mg daily dose through Week 52 2, 4
  • Maintenance therapy shows more consistent response rates across biologic exposure groups (61% biologic-naive, 60% with 1 prior biologic, 55% with 2+ prior biologics) 4

Clinical Positioning

Optimal Patient Selection

  • Ozanimod is best positioned before biologics given the greater effect size in biologic-naive versus biologic-exposed patients during induction 1
  • Typical candidates include patients requiring more than one course of steroids per year after starting aminosalicylates or thiopurines 1
  • Can be used in any patient who fails or loses response to aminosalicylates, regardless of steroid requirement 1

Alternative Positioning Scenarios

  • After biologic failure or loss of response in patients who have failed biologics 1
  • For maintenance after induction with other advanced therapies including ciclosporin, biologics, or JAK inhibitors 1
  • In patients achieving remission with biologics but concerned about injection inconvenience or safety 1

Critical Monitoring Requirements

Baseline Assessments (Before Initiation)

  • Complete blood count 1
  • Electrocardiogram to screen for cardiac conduction abnormalities 1
  • Liver enzymes 1
  • Ophthalmic examination of fundus and macula if history of diabetes, uveitis, or macular edema exists 1
  • VZV antibody testing in patients without chickenpox history or confirmed vaccination 1

During Treatment Monitoring

  • Blood pressure: Monitor for 3 months after initiation, then every 6 months 1
  • Lymphocyte count: Assess every 3 months (expect 49% reduction from baseline with 0.92 mg dose) 1, 3
  • Liver function: Assess at 1 month, then every 3 months 1
  • Infection surveillance: Monitor during treatment and up to 3 months after discontinuation 1
  • Respiratory function: Assess if clinically indicated 1

Important Safety Considerations

Contraindications and Precautions

  • Discontinue other immunosuppressive therapies before starting ozanimod 1
  • Avoid drugs that slow heart rate or AV conduction 1
  • Do not use during active infection 1
  • Avoid in pregnancy 1, 5
  • Contraindicated in clinically significant cardiovascular disease, type II second-degree or third-degree AV blocks 5

Comparative Safety Profile

  • Ozanimod discontinuation due to adverse events was only 1-4% in the True North trial, compared to up to one-third with thiopurines 1
  • No black-box warnings unlike some TNF inhibitors and JAK inhibitors 1
  • No evidence of immunogenicity observed in clinical trials 1
  • Risk of serious infections and malignancies was low in UC clinical trials 1

Real-World Effectiveness Considerations

  • Patients with prior biologic exposure may require additional time to respond to ozanimod therapy 4
  • Real-world data shows week 10 clinical response rates of 58% and remission rates of 53% in treatment-refractory patients, though long-term maintenance effectiveness was more modest (25% at week 52) 6
  • Greater lymphocyte count reduction (>75%) correlates with numerically higher response rates (80% vs 54% clinical response) 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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