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. 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.  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 and even lower with subsequent treatments than the percentage showing improvement with the first treatment.   

  • Cost:  These drugs are very expensive and so may not be available to patients in all countries.  When you are considering a treatment it is helpful to check the cost and coverage under insurance plans with your doctor and your pharmacist.  (See the fact sheet Managing Costs of Medicine for Inflammatory Bowel Disease for more information.)

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. 

  • It is administered as a set dose to persons of all sizes (300 mg) intravenously 3 times in 6 weeks to start and then every 8 weeks thereafter. In some who have not fully responded or who lose response before 8 weeks is up, dosing may be administered every 4 weeks.

  • 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 (20%) will respond and about 1 in 3 to 1 in 4 persons (25%-33%) who respond will show maintained improvement over time. 

  • In Crohn’s disease, about 1 in 10 persons (10%) with active disease will respond and about 1 in 6 persons (17%) who respond will show maintained improvement over time.

  • It does not seem that Vedolizumab is effective at closing Crohn’s disease related fistulas.

  • Side effects and complications:  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 lymphocytes (inflammatory cells) to the bowel, and even though these cells make up part of the body’s defense against intestinal infection,  the use of his drug does not seem to have any adverse effects in regards to 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 (25%) treated with Ustekinemab will respond and about 1 in 4 persons (25%) who improve will show maintained improvement (remission).

  • In ulcerative colitis, 1 in 9 patients will achieve remission by 8 weeks, however 1 in 4 persons (25%) will improve even if not fully in remission. Of those who respond to dosing within 8 weeks approximately 1 in 5 will be in remission at 10 months and 1 in 4 (25%) will have maintained a benefit even if not fully in remission.

  • Ustekinemab has been used for several years to treat psoriasis

  • Side effects and complications:  These drugs have few side effects. There is no known risk of cancer over time, and only a minimal 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 (33%) will respond and maintain improvement over time.  In Crohn’s disease, studies of related agents are underway.

  • The drug seems to maintain its benefit even in persons who have already used another biological therapy.

  • Tofacitinib is currently used to treat rheumatoid arthritis

  • Side effects and complications:  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. If this happens it will occur by 6 months of use and if it has not occurred by that point it likely will not occur. It is unclear if the increased cholesterol poses a risk for future heart disease. There is an increased risk of developing shingles at a rate of 1 in 20 so it is recommended that patients using this drug be vaccinated with the non-live shingles vaccine (Shingrix). In 2019 it was reorted from rheumatoid arthritis studies that there is an increased risk of develop clots in leg and lung veins when 10 mg twice daily dosing was used for over 100 days. As 10 mg twice daily is the dose used in ulcerative colitis it is recommend to reduce the dose 12 to 14 weeks of use.

 

References

 

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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. Inflammatory Bowel Diseases. 2016 ;22(7):1737-43.

 

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

 

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. New England Journal of Medicine. 2017 May 4;376(18):1723-1736.

 

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. Inflammatory Bowel Diseases. 2017 Jan;23(1):97-106.

Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as Induction and Maintenance Therapy  for Ulcerative Colitis. N Engl J Med 2019; 381: 1201-1214.

 

Last reviewed: March 2020

For more information about IBD and its treatment please visit: 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. 

2017 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).

© 2017 The IBD Clinical and Research Centre

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