Induction of remission
The second category focuses on the induction of remission [through treatment].
First, [the evidence for] 5-aminosalicylates (5-ASAs) in mild to moderate disease is very weak. No data show 5-ASAs, and mesalamine in particular, to be effective at the induction of remission.
The same has been shown for the use of antibiotics; by themselves, there really is no role.
There is no role for immunosuppressants. No comparative [evidence] shows that 6-mercaptopurine or azathioprine is better than placebo in the short to medium time range. Although we recognize that these drugs would be helpful in steroid-sparing and weaning [patients] off steroids for the induction of remission, there is no significant benefit.
Corticosteroids may be helpful in symptom derailment, but they are not predictable in the resolution of mucosal disease. Even for mild to moderate and moderate to severe disease, they do not seem to have the best evidence as it relates to the induction of disease [remission].
Biologics (including the tumor necrosis factor [TNF]-alpha antagonists of adalimumab; vedolizumab and natalizumab; and ustekinumab) have positive support for the induction of disease remission, which makes sense based on the literature.
Biosimilars
[The third category] focuses on biosimilars. We are certainly seeing this more, and challenges from our pharmacy benefits service as to whether we can save money.
The evidence is that biosimilars are effective and noninferior compared with the parent agents. They can be used for induction and maintenance [therapy in] naive patients. There is still a concern about the cross-immunologic upregulation using biosimilars after a parent drug that could not necessarily be evidence-supported. For biosimilars, beware if you start switching [to them] in patients who are well controlled. I think [the use of them for induction and maintenance therapy] seems to be strongly supported based on this current recommendation.
Maintenance of remission
The fourth category focuses on the maintenance of remission once you have attained mucosal [healing].
Again, the 5-ASA products have no role; there is really no value. Steroids are not used for long-term treatment and have variable results in the short-term induction of remission.
Budesonide may be used in patients with ileitis or right-sided colon disease, but the caveat from this recommendation is not to go beyond 4 months. We have seen adrenal insufficiency in some patients. Again, it is not a good drug in the long term, and you should consider steroid-sparing modalities.
Biologics, including natalizumab, vedolizumab, ustekinumab, and adalimumab, have evidence to support their long-term use in the maintenance phase—that is, once initial remission and mucosal healing have been achieved.
The Postoperative Patient
[The fifth category of interest] focuses on the postoperative patient. It is very difficult to make a decision here.
Data support that [high-risk patients should be put back on biologic therapy within 4 weeks of surgery]. Patients at high risk for recurrence include those with previous surgery for Crohn disease, those who smoke (if they are smokers, you should tell them to stop; that is important and a recommendation in and of itself), and those with penetrating disease. Once [patients no longer have] potential infection concerns, restart therapy. It is recommended that patients use combination therapy if there is a concern regarding the development of antibodies. I do not know that it needs to be routine, but the recommendation is that combination therapy would be the preferred approach.
You could make the argument that if a patient is not high-risk and you choose not to restart immunotherapy or a biologic therapy combination, you should go back and do an endoscopic assessment. We would routinely do this within 3-6 months and look for early mucosal relapse in order to then justify therapy at that point based on what we saw.
These are five areas of interest, but there are many other valuable points here. I think this document will be helpful for us, supplying the best evidence and practice recommendations as we move forward in our continued evolution of enhanced care for patients with Crohn disease.
I'm Dr David Johnson. Thanks again for listening.
