• Reference [17]
Evaluating patients who fail treatment while on TNF inhibitor therapy
Step 1 - Check trough TNF inhibitor levels
  • Target trough levels for TNF inhibitors:
    • Adalimumab (Humira®): ≥ 7.5 mcg/ml
    • Certolizumab Pegol (Cimzia®): ≥ 20 mcg/ml
    • Golimumab (Simponi®): unknown
    • Infliximab (Remicade®): ≥ 5 mcg/ml
Step 2
  • If trough levels are adequate, suspect drug failure and consider switching to another drug class
  • If trough levels are low, check for anti-drug antibodies
    • Low/absent trough with no anti-drug antibodies
      • Possible pharmacokinetic failure
      • Shorten dosing interval, and/or increase dose, and/or add immunosuppressant
    • Absent trough with high-titer anti-drug antibodies
      • Possible immune-mediated failure
      • Change to another TNF inhibitor or use a different class
    • Low trough with low- or high-titer anti-drug antibodies
      • Indeterminate. Consider one of the above approaches.



TOPICAL MESALAMINE
Mesalamine suppository (Canasa®)
  • Active disease dosing
    • 1000 mg once daily at bedtime [12]
  • Maintenance dosing
    • 1000 mg once daily at bedtime [12]
  • Other
    • In active treatment, benefit is seen within 3 - 21 days
    • Suppository effects been shown to reach ∼ 10 cm into the colon [8]
    • See immunosuppressants for more
Mesalamine enema (Rowasa®)
  • Active disease dosing
    • 4 grams once daily at bedtime [12]
  • Maintenance dosing
    • 2 - 4 grams once daily, every other day, or less frequently in some regimens [8]
  • Other
    • In active treatment, benefit is seen within 3 - 21 days
    • Enema effects have been shown to reach as far as the splenic flexure in some patients [8]
    • See immunosuppressants for more
TOPICAL STEROIDS
Budesonide foam (Uceris®)
  • Active disease dosing
    • 2 mg twice a day for 2 weeks, then 2 mg once daily for 4 weeks [12]
  • Maintenance dosing
    • Not recommended
  • Other
    • Foam is approved to treat disease that extends up to 40 cm from the anal verge [12]
    • See IBD steroids for more
Budesonide tablet (Uceris®)
  • Active disease dosing
    • 9 mg once daily for up to 8 weeks [12]
  • Maintenance dosing
    • Not recommended
  • Other
    • Budesonide tablets are enteric coated and do not dissolve until they reach the intestine
    • The therapeutic effect is thought to occur largely through local effects in the colon
    • Budesonide undergoes extensive first-pass metabolism and systemic effects are minimized [12]
    • See IBD steroids for more
Hydrocortisone enema (Colocort®, Cortenema®)
  • Active disease dosing
    • 100 mg once daily for 21 days or longer if necessary [12]
  • Maintenance dosing
    • Not recommended
  • Other
    • Clinical response typically seen within 3 - 5 days
    • Enema effects reach the splenic flexure, and have been shown to be beneficial in some patients with transverse and ascending disease [12]
    • See IBD steroids for more
Hydrocortisone foam (Cortifoam®)
  • Active disease dosing
    • One applicatorful 1 - 2 times a day for 2 - 3 weeks, and every second day thereafter [12]
  • Maintenance dosing
    • Not recommended
  • Other
    • Clinical response typically seen within 5- 7 days [12]
    • Foam effects have been shown to reach ∼ 15 - 20 cm into the colon [8]
    • See IBD steroids for more
ORAL STEROIDS
Prednisone
  • Active disease dosing
    • 40 - 60 mg a day until significant improvement
    • Then taper dose by 5 - 10 mg/week until dose of 20 mg is reached
    • From 20 mg, taper dose by 2.5 mg/week [8]
  • Maintenance dosing
    • Not recommended
  • Other
ORAL AMINOSALICYLATES
Balsalazide (Colazal®, Giazo®)
  • Active disease dosing
    • Colazal capsule: 2250 mg three times a day
    • Giazo tablet: 3300 mg two times a day [12]
  • Maintenance dosing
    • 2000 - 6750 mg a day given in divided doses [8]
  • Other
Mesalamine (Apriso®, Asacol® HD, Delzicol®, Pentasa®, Lialda®)
  • Active disease dosing
    • Asacol HD: 1600 mg three times a day
    • Delzicol: 800 mg three times a day for 6 weeks
    • Pentasa: 1000 mg four times a day for 8 weeks
    • Lialda: 2400 - 4800 mg once daily [12]
  • Maintenance dosing
    • Apriso: 1500 mg (4 capsules) once daily
    • Delzicol: 1600 mg per day given in divided doses
    • Lialda: 2400 mg once daily [12]
  • Other
Olsalazine (Dipentum®)
  • Active disease dosing
    • 1500 - 3000 mg a day given in 2 divided doses [8]
  • Maintenance dosing
    • 500 mg two times a day [12]
  • Other
    • Efficacy of olsalazine in active UC has not been conclusively established [8]
    • See immunosuppressants for more
Sulfasalazine (Azulfidine®, Azulfidine EN®)
  • Active disease dosing
    • 4000 - 6000 mg a day given in 4 divided doses [8]
  • Maintenance dosing
    • 2000 - 4000 mg a day given in divided doses [8]
  • Other
    • Dosing intervals should not exceed 8 hours
    • Maintenance therapy with 4000 mg/day is most effective, but up to 25% of patients will not tolerate this dose [8]
    • See immunosuppressants for more
THIOPURINES
Azathioprine (Imuran®)
  • Dosing
    • 2.5 mg/kg/day given once daily or in divided doses [1,8]
  • Other
    • Primary benefit is in maintenance therapy because of slow onset of action (up to 3 - 6 months) [8]
    • See immunosuppressants for more
Mercaptopurine (6-MP)
  • Dosing
    • 1.0 - 1.5 mg/kg/day given once daily [1]
  • Other
    • Primary benefit is in maintenance therapy because of slow onset of action (up to 3 - 6 months) [8]
    • See immunosuppressants for more
BIOLOGICALS
Infliximab (Remicade®)
Adalimumab (Humira®)
  • Dosing
    • Day 1: 160 mg
    • Day 15: 80 mg
    • Day 29 and on: 40 mg every other week [12]
  • Other
    • Tumor necrosis factor inhibitor
    • See biologicals for more
Golimumab (Simponi®)
  • Dosing
    • Starting: 200 mg at Week 0, followed by 100 mg at Week 2
    • Maintenance: 100 mg every 4 weeks [12]
  • Other
    • Tumor necrosis factor inhibitor
    • See biologicals for more
Vedolizumab (Entyvio®)
  • Dosing
    • Starting: 300 mg IV at Weeks 0, 2, and 6
    • Maintenance: 300 mg IV every 8 weeks [12]
  • Other
    • Anti-integrin antibody that inhibits T-cell migration
    • Approved for use in patients who do not respond to tumor necrosis factor inhibitors or immunosuppressants [12]
    • See vedolizumab vs placebo study below
    • See biologicals for more
TOFACITINIB (XELJANZ®)
Tofacitinib (Xeljanz®)
CYCLOSPORINE
Cyclosporine
  • Active disease dosing
    • Starting: 2 - 4 mg/kg/day via IV infusion. May be given in doses or as a continuous infusion.
    • Target blood concentration is 200 - 250 ng/ml
    • After response is seen with IV therapy, patients are switched to oral therapy at a dose that is twice the daily IV dose
    • Oral cyclosporine (Neoral or Gengraf) is given in 2 divided doses. Target trough concentration for oral therapy is 200 - 250 ng/ml.
    • Oral cyclosporine should be overlapped with a thiopurine and continued for 2 - 3 months before tapering [13,14]
  • Maintenance dosing
    • Not recommended
  • Other
    • Most patients respond within 7 days
    • Patients who do not respond to IV cyclosporine should be considered for colectomy
    • Patients treated with cyclosporine and steroids should receive sulfamethoxazole/trimethoprim prophylaxis (1 DS tablet once daily) to prevent Pneumocystis jirovecii pneumonia
    • Cyclosporine microemulsion (Neoral and Gengraf) has greater bioavailability that standard cyclosporine (Sandimmune) [13,14]
    • See cyclosporine vs infliximab study below
    • See immunosuppressants for more