Ulcerative Colitis (UC) is a chronic inflammatory bowel disease that primarily affects the large intestine, including the colon and rectum. This condition leads to inflammation and the development of small ulcers in the lining of the bowel, which can cause symptoms such as abdominal pain, diarrhea, and rectal bleeding. UC is characterized by periods of active symptoms, known as flares, interspersed with times of remission where symptoms subside. While the exact cause remains unclear, it is thought to involve an immune system malfunction where the body mistakenly attacks healthy tissue.
Understanding Biologics
Biologics are a class of advanced medications derived from living organisms, such as proteins, sugars, DNA, cells, or living tissue. They differ significantly from traditional small-molecule drugs, which are chemically synthesized compounds. Biologics are much larger and more complex molecules, often containing thousands of atoms, compared to small-molecule drugs that may have only dozens of atoms.
These medications work by targeting specific components of the immune system that contribute to inflammation. Instead of broadly suppressing the entire immune system, biologics are designed to block particular inflammatory pathways. Some bind to specific proteins or cells, while others modulate immune system activity. This targeted approach aims to reduce inflammation and promote healing in conditions like ulcerative colitis.
Specific Biologic Therapies for Ulcerative Colitis
Several classes of biologics are used to manage ulcerative colitis by targeting different inflammatory pathways. One prominent class is TNF-alpha inhibitors, which include medications like infliximab, adalimumab, and golimumab. These drugs work by binding to and blocking tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine central to UC inflammation.
Another class of biologics is integrin receptor antagonists, with vedolizumab being an example. These medications target specific proteins called integrins, which are found on the surface of certain immune cells. By blocking the interaction between these integrins and adhesion molecules in the gut, they prevent inflammation-causing lymphocytes from migrating from the bloodstream into the gastrointestinal tract, thereby reducing gut inflammation.
Interleukin-12/23 inhibitors, such as ustekinumab, are another class. Interleukin-12 and interleukin-23 are cytokines that promote bowel inflammation in UC. Ustekinumab works by binding to the shared p40 protein subunit of both interleukin-12 and interleukin-23, inhibiting their signaling and reducing inflammation.
While not technically biologics, Janus kinase (JAK) inhibitors are oral small-molecule drugs that are often discussed alongside biologics for their targeted action. Medications like tofacitinib and upadacitinib block the activity of JAK enzymes inside immune cells, which transmit signals leading to inflammation. By inhibiting these enzymes, JAK inhibitors decrease the immune system’s inflammatory reaction.
Patient Candidacy and Treatment Considerations
Patient Candidacy
Biologic therapy is considered for individuals with moderate to severe ulcerative colitis who have not responded to conventional treatments, such as corticosteroids or immunomodulators, or who cannot tolerate these therapies.
Administration
Biologics are administered either through intravenous (IV) infusions or via subcutaneous injections that can be self-administered at home. For example, infliximab and vedolizumab are infusions, while adalimumab and golimumab are subcutaneous injections. Ustekinumab may start with an IV infusion, followed by subcutaneous injections.
Side Effects
Like all medications, biologics can have side effects. Common reactions may include redness, itching, swelling, or pain at the injection site, as well as headaches, fever, or chills. Because biologics modulate the immune system, there is an increased susceptibility to infections, including the reactivation of latent infections like tuberculosis or hepatitis B, requiring screening before treatment. A low, increased risk of certain cancers, such as lymphoma, has been associated with some biologic drugs.
Monitoring
During treatment with biologics, regular monitoring is advised to assess the drug’s effectiveness and to detect any side effects. This monitoring may include blood tests for inflammation markers, drug concentrations, and anti-drug antibodies, which can affect efficacy. While biologics can induce and maintain remission, some individuals may lose response over time, potentially requiring dose adjustments or a switch.