Biological therapy for inflammatory bowel disease
[9] The previous treatment options had many shortcomings, and the introduction of biological therapy changed the way physicians treat Crohn's disease and ulcerative colitis.
It wasn't until the 1900s that the newly emerging class of naturally derived medications such as sera, vaccines, and antitoxins began to be referred to as biologics.
Today, biological therapy most commonly refers to the use of proteins, such as monoclonal antibodies, to regulate the immune system in the treatment of disease.
[16] Infliximab as well as other TNF inhibitors like adalimumab, certolizumab, and golimumab are currently the most common biologics used in the treatment of both Crohn's disease and ulcerative colitis.
[11] Prior to the development of biological therapy as a modality to treat IBD, other medications that modulate the immune system—including 5-aminosalicylates, steroids, azathioprine, and other immunosuppressants—were primarily used in treatment.
[17] The other medications like 5-aminosalicylates and azathioprine are often used to reduce steroid use while maintaining remission, but their actual effect on the state of the disease and the need for surgery remains unknown.
[17] Patients with Crohn's disease that developed complications, including fistulae (= abnormal connections to the bowel) were treated with surgery.
[17] They proved to be very effective in some patients, shifting treatment goals from simply improving symptoms to actually changing the course of the disease by reversing mucosal inflammation and preventing long-term complications and surgery.
[26] It was found to have efficacy over placebo medications for 10 weeks in the treatment of moderate to severe Crohn's disease in one large trial.
Since, it has been approved to also treat psoriatic arthritis, ankylosing spondylitis, and moderately to severely active ulcerative colitis.
During active periods of disease, cell adhesion molecules on the vascular endothelium increase in response to various proinflammatory cytokines.
Integrin receptor antagonists block the interaction and prevent the migration of inflammatory cells to disease sites.
Interleukin antagonists, the most recent class of biologics available for use in IBD, inhibit the action of IL-12 and IL-23 by binding to the p40 protein subunit that is found on both of these cytokines.
They can't be delivered orally because the harsh environment of the gastrointestinal tract would breakdown the drug before it could reach the diseased tissue.
Because systemic administration results in blockading the same pathway in both healthy and diseased tissue, pharmacology is exaggerated leading to many side effects such as lymphoma, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, injection site reactions, and additional systemic side effects.
[29] The treatment of inflammatory bowel diseases, with an estimated direct cost of $5.9 billion annually, poses a significant economic burden on the health care system.
[23] In clinical practice, less than 50% of patients who showed an initial positive response to biological therapy were in remission after one year.
[10] The development of anti-drug antibodies can be reduced by limiting any times when there is no biologic present in the body and by taking other immunosuppressants (such as thiopurines or methotrexate) in combination.
Brazikumab and risankizumab are both IL-23 specific antagonists, opposed to ustekinumab which targets both IL-12 and IL-23, that have shown efficacy in phase 2 trials for Crohn's disease.
The hope is that etrolizumab can show similar efficacy to natalizumab while avoiding the specific cellular target that is believed to have caused the instances of progressive multifocal leukoencephalopathy.
The general consensus in the field is that oral delivery of biologics directly to the diseased tissue could greatly reduce side effects, the development of anti-drug antibodies, and the cost of treatment.
