Crohn's disease is an inflammatory condition of unknown etiology that can affect any portion of the gastrointestinal tract from the mouth to the perianal area. Its transmural inflammatory nature coupled with the variability of organ distribution gives rise to a spectrum of clinical presentations, each of which has to be considered separately in deciding upon the proper therapeutic approach.
Three anti-TNF therapies are approved for treatment of Crohn's disease in adults in the United States and all are effective in treatment of luminal Crohn's disease: infliximab, adalimumab, and certolizumab pegol (which is not approved in Europe).
The selection among these three drugs will depend upon several issues:
- Adalimumab and certolizumab pegol have an advantage of subcutaneous administration rather than intravenous administration required for infliximab. The former requires administration every two weeks and the latter every four weeks. However, certolizumab's labeling requires it to be reconstituted by a healthcare professional. The manufacturer is addressing this restriction by a program that uses a home nursing service to dispatch a healthcare professional to the patient's home.
- Physicians will need to ensure that self-administration with adalimumab and/or certolizumab pegol does not lead to incomplete compliance and thereby loss of efficacy.
- Adalimumab has been associated with injection site reactions and pain at a higher frequency than certolizumab pegol, although the two have not been directly compared.
- Certolizumab will be priced 5 percent lower than adalimumab, but the relative prices will be expected to vary at local formularies. The manufacturer is also providing co-payment assistance in all states but Massachusetts.
- Infliximab and adalimumab have an advantage in a broader labeling indication; both are approved for reducing signs and symptoms of Crohn's disease and inducing and maintaining clinical remission while certolizumab pegol does not have an explicit maintenance indication. However, the remission rates in clinical trials have not revealed an important distinction from remission rates with the other two drugs.
- Experience with adalimumab for patients who have lost response to or had an adverse reaction to infliximab is greater than with certolizumab pegol, although preliminary data suggest that certolizumab can also be effective in such patients.
- Infliximab has demonstrated efficacy in the treatment of fistulizing Crohn's disease while efficacy of adalimumab and certolizumab pegol has not yet been established in placebo-controlled trials. Nevertheless, subgroup analysis of fistulas during induction and maintenance trials suggests that adalimumab will have similar efficacy with perianal fistulas as infliximab. There are no data for certolizumab pegol.
- The safety record with infliximab and adalimumab is longer than with certolizumab pegol. Anti-TNF therapy should not be initiated in patients with active infections including chronic or localized infections. Before treatment, patients should be evaluated for tuberculosis risk factors and tested for latent infection. These issues are discussed elsewhere.
- Neither infliximab nor adalimumab nor certolizumab pegol can be recommended as safe agents for the treatment of Crohn's disease in pregnancy, but in urgent situations, when no reasonable therapeutic alternative to anti-TNF agents is available, infliximab may be the preferred drug because of a larger body of safety data.
Infliximab
Prior to the introduction of biologic agents in the late 1990s, patients with moderate to severe Crohn's disease or fistulous Crohn's disease had few nonsurgical options. Infliximab is a chimeric mouse/human monoclonal antibody against tumor necrosis factor alpha. It has provided a powerful new tool for the treatment of moderately to severely active Crohn's disease that is refractory to conventional therapy. Clinical trials and experience have demonstrated significant utility of infliximab for induction of remission in moderately active, steroid refractory Crohn's disease, improvement in quality of life, and maintenance of remission in these patients for up to 54 weeks after initial infusion. Treatment can be effective in patients with and without fistulizing disease (including those with internal fistulas such as entero-vesicle fistulas).
At the present time, infliximab should not be used as first line therapy until appropriate clinical trials have demonstrated its value as primary therapy and the long-term effects of infliximab have been able to be fully evaluated. Infliximab should be used primarily in patients refractory to standard therapy, in order to help taper patients off steroids and transition them to effective long-term maintenance therapy using infliximab plus 6-MP or azathioprine. In patients with fistulas, infliximab should also be reserved for those Crohn's disease patients whose fistulas have been refractory to standard therapy. Patients should be evaluated for latent tuberculosis infection prior to its administration.
Adalimumab
The role of adalimumab for treatment of Crohn's disease is evolving. Similar to infliximab, it is probably best reserved for patients refractory to primary therapy or who are steroid dependent. As noted above, the decision whether to use adalimumab, certolizumab pegol, or infliximab in such patients will mostly be influenced by the convenience of subcutaneous administration of adalimumab, and less frequent dosing with certolizumab pegol compared with the larger body of safety and efficacy data with infliximab. Adalimumab may also be an option for patients who have lost response to or had an adverse reaction to infliximab.
Certolizumab pegol
Certolizumab pegol is a humanized monoclonal antibody Fab fragment linked to polyethylene glycol that neutralizes tumor necrosis factor.
References: UTD