Etrasimod, sold under the brand name Velsipity, is an oral medication approved for adults with moderately to severely active ulcerative colitis. This condition is a form of inflammatory bowel disease characterized by persistent inflammation and ulceration in the lining of the large intestine. Ulcerative colitis can cause disruptive symptoms, including diarrhea, rectal bleeding, and abdominal pain, impacting a person’s quality of life.
How Etrasimod Works for Ulcerative Colitis
Etrasimod belongs to a class of drugs known as sphingosine-1-phosphate (S1P) receptor modulators. These modulators work by interacting with specific receptors on the surface of immune cells called lymphocytes. Etrasimod has a high affinity for S1P receptor subtypes 1, 4, and 5.
By binding to these receptors, the drug traps lymphocytes within the lymph nodes, preventing these inflammatory cells from traveling to the colon. This leads to a reduction in activated lymphocytes in the intestinal tissues, which decreases the inflammatory response that drives the disease. After about two weeks of treatment, the total count of lymphocytes in the blood is typically reduced by half.
Clinical Trial Efficacy
The effectiveness of etrasimod was established in two Phase 3 clinical trials: ELEVATE UC 52 and ELEVATE UC 12. These studies evaluated the drug’s ability to induce and maintain remission in adults with moderate to severe disease. The primary goal was clinical remission, a composite score assessing stool frequency, rectal bleeding, and the colon’s appearance during an endoscopy.
In the ELEVATE UC 52 study, 27% of patients receiving etrasimod achieved clinical remission after 12 weeks, compared to 7% of those taking a placebo. For patients who continued the treatment, 32% were in remission at 52 weeks, versus 7% in the placebo group. The ELEVATE UC 12 trial showed that 26% of patients on etrasimod reached remission after 12 weeks, compared to 15% on placebo.
The trials also measured secondary endpoints like endoscopic improvement and symptomatic remission. In ELEVATE UC 52, a significantly higher number of patients on etrasimod also achieved corticosteroid-free remission by the end of the study.
Administration and Dosing
Etrasimod is administered as a once-daily 2 mg oral tablet. This tablet can be taken with or without food, but taking the first dose with food may help lessen the drug’s initial effect on heart rate.
Before starting treatment, patients undergo several pre-treatment screenings to ensure the medication is appropriate. This process includes an electrocardiogram (ECG) to assess heart rate and rhythm, as this class of drugs can cause a temporary slowing of the heart. An eye exam is required to check for macular edema, and blood tests are performed to check liver function and obtain a baseline lymphocyte count.
Potential Side Effects and Safety
In the clinical trials, the most commonly reported adverse effects were headache, dizziness, and fever. Some patients also experienced elevated liver enzymes, which is why liver function is monitored. These side effects were generally mild to moderate in severity.
A known effect of S1P receptor modulators is a temporary decrease in heart rate when starting the medication. This was observed within the first few hours after the initial dose, with some patients experiencing bradycardia, or a slow heart rate. For this reason, cardiac function is monitored at the beginning of treatment. There is also a potential for atrioventricular block, a delay in the heart’s electrical conduction, though this was uncommon.
Because the drug works by sequestering immune cells, there is an increased risk of certain infections, like urinary tract and lower respiratory tract infections. The overall rate of infections in clinical studies, however, was comparable between the etrasimod and placebo groups. Other less common but serious risks include liver injury and macular edema, a buildup of fluid in the retina. Patients are monitored for these conditions while on the medication.