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In Crohn’s disease, adalimumab and infliximab plus azathioprine are best for inducing and maintaining remission

Hazlewood GS, Rezaie A, Borman M, et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn`s disease: a network meta-analysis. Gastroenterology. 2015;148:344-54.

Review question

In people with Crohn’s disease, which drug treatments are best for inducing and maintaining remission?

Background

Crohn’s disease causes inflammation of the lining of the digestive tract. This can cause abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. There are several drug treatments available that can induce and maintain remission in Crohn’s disease. These include immunosuppressant drugs (i.e., azathioprine/6-mercaptopurine and methotrexate) and anti–tumor necrosis factor (TNF) therapy (i.e., infliximab, adalimumab, and certolizumab).

How the review was done

The researchers did a systematic review, searching for studies that were published up to June 2014.

They found 39 randomized controlled trials with 7804 people.

The key features of the trials were:

  • participants were adults who had established Crohn’s disease;
  • participants started treatment with azathioprine/6-mercaptopurine, methotrexate, approved anti-TNF therapies (infliximab, adalimumab, and certolizumab), or vedolizumab , alone or in combination;
  • treatments were compared with placebo or another active agent;
  • remission was measured using the Crohn’s Disease Activity Index; and
  • people were followed for 4 to 17 weeks for induction of remission and for ≥ 24 weeks for maintenance of remission.

Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

What the researchers found

Infliximab, infliximab plus azathioprine, adalimumab, and vedolizumab increased induction and maintenance of remission more than placebo and more than azathioprine/6-mercaptopurine.

Infliximab plus azathioprine and adalimumab increased induction and maintenance of remission more than certolizumab.

The risk of medication discontinuation as a result of adverse events was:

  • higher for azathioprine/6 mercaptopurine, methotrexate, infliximab, and infliximab plus azathioprine compared with placebo;
  • higher for azathioprine/6-mercaptopurine and methotrexate compared with anti-TNF monotherapy with adalimumab, vedolizumab, or certolizumab but not infliximab;
  • lower for adalimumab compared with all treatments except vedolizumab and infliximab plus methotrexate; and
  • lower for vedolizumab compared with azathioprine, methotrexate, infliximab, and infliximab plus azathioprine.

Conclusion

In people with Crohn’s disease, adalimumab and infliximab plus azathioprine are the most effective drugs for induction and maintenance of remission of Crohn’s disease.

Drug treatments for the induction and maintenance of remission in Crohn’s disease

Outcomes

Effect of treatment*

Induction of remission

Infliximab, infliximab plus azathioprine, adalimumab, and vedolizumab increased induction of remission more than placebo

 

Infliximab, infliximab plus azathioprine, and adalimumab increased induction of remission more than azathioprine/6-mercaptopurine

 

Infliximab plus azathioprine and adalimumab increased induction of remission more than certolizumab

Maintenance of remission

All treatments except infliximab plus methotrexate increased maintenance of remission

 

Methotrexate monotherapy did not differ from other treatments

 

Adalimumab, infliximab, and infliximab plus azathioprine increased maintenance of remission more than azathioprine/6-mercaptopurine

 

Infliximab plus azathioprine and adalimumab increased maintenance of remission more than certolizumab

 

Adalimumab increased maintenance of remission more than vedolizumab

*Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.



Related Topics


Glossary

Placebo
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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