Infliximab versus cyclosporine for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomized trial

by Anna Gawrys, Mercer University College of Pharmacy

 

The American College of Gastroenterology Clinical Guidelines for Ulcerative Colitis in Adults recommends oral aminosalicylates, topical mesalamine, or topical steroids as first line treatment.  Oral prednisone or infliximab is recommended for refractory patients. [1]

Both Remicade® (infliximab) and cyclosporine are immunospuppressive agents that decrease inflammation [2]; however, it is stated that there has been no comparative evaluation of both agents [3]. Infliximab has a Food and Drug Administration (FDA) indication for ulcerative colitis [4] while cyclosporine does not [5].

Title: Infliximab versus cyclosporine for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomized trial [3]

Design Mixed method, open-label, pragmatic randomized trial; N= 270
Objective To compare efficacy of infliximab versus cyclosporine in refractory treatment of severe ulcerative colitis
Study Groups Infliximab group (n= 135) and cyclosporine group (n= 135)
Methods Patients with severe ulcerative colitis who failed to respond to intravenous hydrocortisone within five days were randomized to receive infliximab or cyclosporine. The efficacy was measured every six months with the last one at two years.
Duration June 2010 – February 2013
Primary Outcome Measure Quality-adjusted survival measured by Ulcerative Colitis Questionnaire (CUCQ) score
Baseline Characteristics Infliximab (n= 135) Cyclosporine (n= 135)
Age, yr (range) 35 (27 – 50) 36 (27 – 50)
Female, n (%) 46 (34) 54 (40)
White, n (%) 126 (94) 124 (93)
Current or ex-smoker, n (%) 72 (55) 59 (44)
Condition severity, severe, n (%) 97 (73) 95 (73)
Duration of symptoms for current episode, d (range) 21 (14 – 42) 28 (14 – 42)
Results Quality-adjusted survival CUCQ score
Infliximab Cyclosporine p-value
Mean CUCQ 564 587 p= 0.603
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: Infliximab:

malignancies (1%)

Cyclosporine:

malignancies (1%); renal disorders (2%)

Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions There was no significant difference between cyclosporine and infliximab in clinical effectiveness.

 

This study shows that infliximab and cyclosporine are equally effective for patients who do not respond to prednisone treatment. Although no significant differences were found between those two agents, the increased side effect profile of cyclosporine suggests that infliximab is a safer option. Cyclosporine is not in current guidelines nor does it carry FDA approval for ulcerative colitis, but it remains a viable option for patients who are refractory to other treatments.

 

References

  1. Kornbluth A, Sachar D. Ulcerative Colitis in Adults. American College of Gastroenterology. http://gi.org/guideline/ulcerative-colitis-in-adults/. Published March 2010. Accessed June 28, 2016.
  2. Ulcerative Colitis. National Institute of Diabetes and Digestive And Kidney Diseases. http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/ulcerative-colitis/Pages/facts.aspx Published September 2014. Accessed June 28, 2016.
  3. Chang KH, Burke JP, Coffey JC. Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis. Int J Colorectal Dis. 2013;28(3):287-93.
  4. Remicade® (infliximab) [package insert]. Malvern, PA: Centocor Ortho Biotech, Inc.; 2011
  5. Sandimmune® (cyclosporine) [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2015
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