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New Biological Medicines

for Inflammatory Bowel Disease (IBD)

KEY POINTS:

  • Biological therapy refers to the use of medication that is tailored to specifically target an immune or genetic mediator of disease. This approach to treatment has been used since the 1990's and new biological medicines continue to be developed.

  • Antibodies to tumor necrosis factor (Anti–TNF) medicines were the first biological therapies developed for IBD. Anti-TNF drugs are very effective at treating persons with either Crohn’s disease or ulcerative colitis to settle active disease and to maintain improvement over time (remission). See the Fact Sheet on Anti-TNF medicines for IBD for more detailed information.

  • As new biological medicines are developed, they are often evaluated for use in a variety of serious health problems including Crohn’s disease and ulcerative colitis. Once they have been shown to be safe and effective, drug companies apply for approval with the government authority for medicines in each country. When they are approved, the approval is for specific diseases and situations (called indications).

  • Newer biological medicines that have been evaluated for Crohn’s disease or ulcerative colitis are vedolizumab (Entyvio), ustekinemab (Stelera), tofacitinib (Xeljanz or Jakvinus). They are described in more detail below.

  • Since the anti-TNF medicines have been used for a longer period they are often used first in IBD. As they become more widely used, some of these other biological medicines may be used first when it is thought that they may be more helpful to a patient. Even today there are situations where some of the newer biological medicines will be chosen first, ahead of the anti-TNF medicines.

  • When treatment with the first biological medicine has not been successful in either Crohn’s disease or ulcerative colitis, a second biological medicine may be tried. The percentage of patients showing improvement is often lower with the second treatment than the percentage showing improvement with the first treatment. 

  • These drugs are very expensive and so may not be available to patients in all countries.

 

Vedolizumab

  • Vedolizumab (Entyvio) is a newer medicine that is administered intravenously. It is an antibody to a protein called alpha4, beta7 and interferes with the influx of inflammatory cells called lymphocytes into the bowel.

  • Vedolizumab is effective at settling active Crohn’s disease and active ulcerative colitis and maintaining improvement (remission). In Canada it has been approved for treatment of both diseases.

  • In ulcerative colitis, about 1 in 5 persons will respond and about 1 in 3 to 1 in 4 persons who respond will show maintained improvement over time.

  • In Crohn’s disease, about 1 in 10 persons with active disease will respond and about 1 in 6 persons who respond will show maintained improvement over time.

  • This medicine has few side effects. There is no known risk of serious infections or cancer over time.

  • Because this drug blocks the influx of inflammatory cells to the bowel, it remains to be seen if persons using these drugs will have worse outcomes if they acquire intestinal infections.

 

Ustekinemab

  • Ustekinemab (Stelera) is administered intravenously or as an under the skin injection. It is an antibody to a protein called interleukin 12/interleukin 23. It interferes with intestinal and circulating inflammation.

  • In Crohn’s disease, about 1 in 4 persons treated with Ustekinemab will respond and about 1 in 4 persons who improve with show maintained improvement (remission).

  • In ulcerative colitis, studies of this agent are underway.

  • Ustekinemab has been used for several years to treat psoriasis.

  • These drugs have few side effects. There is no known risk of cancer over time, however there is a mild increased risk of infections.

 

 

Tofacitinib

  • Tofacitinib (Xeljanz or Jakvinus) is taken in pill form. It blocks a protein called janus kinase (JAK) which is important in the inflammatory response in IBD. It has not yet been approved for use in Canada in IBD.

  • In ulcerative colitis, about 1 in 3 persons will respond and maintain improvement over time.

  • In Crohn’s disease, studies of related agents are underway.

  • Tofacitinib is currently used to treat rheumatoid arthritis.

  • These drugs have few side effects. There are rare reports of acute bowel complications like perforations (holes) in the bowel. There are reports of persons using these agents having increased blood levels of cholesterol. It is unclear if these increases pose a risk for future heart disease. There is an increased risk of getting shingles events in users of Tofacitinib.

 

More information:

 

 

References

Leung Y, Panaccione R. Update on ustekinumab for the treatment of Crohn's disease. Gastroenterol Clin North Am. 2014 Sep;43(3):619-30.

Bernstein CN. Treatment of IBD: Where we are and where we are going. American Journal of Gastroenterology 2015; 110:114-126.

Amiot A, Grimaud JC, Peyrin-Biroulet L, Filippi J, Pariente B, Roblin X, Buisson A, Stefanescu C, Trang-Poisson C, Altwegg R, Marteau P, Vaysse T, Bourrier A, Nancey S, Laharie D, Allez M, Savoye G, Moreau J, Gagniere C, Vuitton L, Viennot S, Aubourg A, Pelletier AL, Bouguen G, Abitbol V, Bouhnik Y; Observatory on Efficacy and of Vedolizumab in Patients With Inflammatory Bowel Disease Study Group and the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif. Effectiveness and Safety of Vedolizumab Induction Therapy for Patients With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2016 Nov;14(11):1593-1601

Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, Panaccione R, Loftus EV Jr, Sankoh S, Fox I, Parikh A, Milch C, Abhyankar B, Feagan BG. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut 2017; 66:839-851..

Dulai PS, Sandborn WJ. Next-Generation Therapeutics for Inflammatory Bowel Disease. Curr Gastroenterol Rep. 2016;18(9):51

Khanna R, Chande N, Vermeire S, Sandborn WJ, Parker CE, Feagan BG. The Next Wave of Biological Agents for the Treatment of IBD: Evidence from Cochrane Reviews. Inflamm Bowel Dis. 2016 ;22(7):1737-43.

Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, Blank MA, Johanns J, Gao LL, Miao Y, Adedokun OJ, Sands BE, Hanauer SB, Vermeire S, Targan S, Ghosh S, de Villiers WJ, Colombel JF, Tulassay Z, Seidler U, Salzberg BA, Desreumaux P, Lee SD, Loftus EV Jr, Dieleman LA, Katz S, Rutgeerts P; UNITI–IM-UNITI Study Group. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016 Nov 17;375(20):1946-1960.

Sands BE, Sandborn WJ, Van Assche G, Lukas M, Xu J, James A, Abhyankar B, Lasch K. Vedolizumab as Induction and Maintenance Therapy for Crohn's Disease in Patients Naïve to or Who Have Failed Tumor Necrosis Factor Antagonist Therapy. Inflamm Bowel Dis. 2017 Jan;23(1):97-106.

Sandborn WJ, Su C, Sands BE, D'Haens GR, Vermeire S, Schreiber S, Danese S, Feagan BG, Reinisch W, Niezychowski W, Friedman G, Lawendy N, Yu D, Woodworth D, Mukherjee A, Zhang H, Healey P, Panés J; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017 May 4;376(18):1723-1736.

Last reviewed: October 2018

For more information and fact sheets about IBD and its treatment please visit: http://www.crohnsandcolitis.ca

Disclaimer: This information is provided for educational purposes only. Always consult a qualified health care professional for your specific care.

Source: This summary provides scientifically accurate information.  It was prepared in a research review by researchers with the IBD Clinical and Research Centre, University of Manitoba with assistance from colleagues in Canada and internationally. 

Acknowledgement: Preparation of this material was supported by funding from the Canadian Institutes of Health Research. 

©2016 Charles N. Bernstein, John R. Walker on behalf of Manitoba IBD Clinical and Research Centre. This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License. You are free to copy and distribute this material in its entirety as long as it is not altered in any way (no derivative works).