What to do for a patient with Active Ulcerative Colitis (AUC) who had achieved endoscopic remission with Tofacitinib (tofacitinib) and now presents with a moderate flare?

Management of Moderate Ulcerative Colitis Flare After Tofacitinib-Induced Remission

For a patient with moderate ulcerative colitis flare who previously achieved endoscopic remission with tofacitinib, dose optimization of tofacitinib to 10 mg twice daily is the most appropriate first-line management strategy.

Initial Assessment

1. Confirm active inflammation:

   • Measure fecal calprotectin (>150 mg/g indicates active inflammation) 1
   • Check CRP (though less informative if previously normal) 1
   • Consider flexible sigmoidoscopy if biomarkers are elevated to assess disease severity 1

2. Rule out infections:

   • Stool studies for C. difficile and other enteric pathogens
   • CMV testing if severe or refractory symptoms

Management Algorithm

Step 1: Tofacitinib Dose Optimization

• If on maintenance dose (5 mg BID):

  • Escalate to induction dose of 10 mg twice daily 2
  • This recaptures response in approximately 55% of patients who lost response after dose reduction 3

• If already on 10 mg BID:

  • Consider extended induction therapy for up to 16 weeks at 10 mg BID
  • Extended induction can achieve clinical response in 52.2% of initial non-responders 2

Step 2: If Inadequate Response to Dose Optimization (after 2-4 weeks)

• Consider switching to a different mechanism of action:

  • Vedolizumab or ustekinumab are preferred options after tofacitinib failure 1
  • Upadacitinib (45 mg once daily) has shown efficacy in patients with previous tofacitinib failure 4

• For more severe symptoms approaching ASUC:

  • Consider hospitalization for IV corticosteroids (methylprednisolone 40-60 mg/day) 1
  • If no response to IV steroids within 3-5 days, consider rescue therapy with infliximab or cyclosporine 1

Step 3: Maintenance After Recapturing Response

• If response is achieved with tofacitinib 10 mg BID:
  • Continue 10 mg BID for 8-16 weeks
  • Consider maintaining at 10 mg BID if:
    • Patient had severe endoscopic disease (Mayo endoscopic score of 3) before flare
    • Patient has history of multiple biologic failures
  • These factors increase risk of losing response with dose reduction 3

Important Considerations

1. Biomarker Monitoring:

   • Fecal calprotectin <50 mg/g (rather than <150 mg/g) may be preferred to confirm endoscopic improvement 1
   • Consider repeat biomarker measurement in 3-6 months if initially elevated 1

2. Safety Monitoring:

   • Monitor for adverse events with tofacitinib, particularly:
     • Infections (incidence rate: 2.1 per 100 patient-years)
     • Herpes zoster (incidence rate: 0.5 per 100 patient-years)
     • Venous thromboembolism (incidence rate: 1.1 per 100 patient-years) 3

3. Combination Therapy:

   • Consider adding an immunomodulator (thiopurine or methotrexate) if monotherapy is ineffective 1
   • Combination therapy is generally more effective than monotherapy 1

Common Pitfalls to Avoid

1. Delayed Escalation:

   • Do not delay appropriate treatment escalation, as this can lead to disease progression and complications 5

2. Inadequate Assessment:

   • Don't rely solely on symptoms; use objective markers of inflammation (biomarkers or endoscopy) to guide treatment decisions 1

3. Premature Dose De-escalation:

   • Patients with severe endoscopic disease or prior biologic failure have higher risk of losing response after dose reduction 3

4. Overlooking Infections:

   • Always rule out infections, particularly C. difficile, before intensifying immunosuppressive therapy 1

By following this structured approach, you can effectively manage a moderate ulcerative colitis flare in a patient who previously achieved endoscopic remission with tofacitinib, optimizing the chance of recapturing remission and preventing disease progression.