Managing Ulcerative Colitis by Blocking S1PR1 with Tamuzimod
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on March 7th, 2025
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Ulcerative colitis is an autoimmune condition where immune cells induce excessive inflammation in the large intestine. These cells are guided to the inflamed tissue by a sphingosine 1-phosphate gradient. While inhibiting this pathway has shown efficacy in treating multiple sclerosis, unselective inhibition can lead to a higher incidence of adverse events. Tamuzimod, a more targeted inhibitor, was recently evaluated in a Lancet study for its potential to manage ulcerative colitis.
The phase 2 clinical trial enrolled 213 individuals, averaging 40.6 years of age, each with at least a 3-month history of ulcerative colitis. Using the modified Mayo Score, which has a maximum severity of 12, the cohort’s average baseline score was approximately 6.7. About 80% of participants were concurrently treated with aminosalicylic acid, and around 25% received corticosteroids. Patients were randomly assigned to receive a 12-week course of either placebo or tamuzimod at two dose levels—60 mg or 30 mg. Tamuzimod specifically targets the S1PR1 variant, with minimal interaction with S1PR2 and S1PR3, thereby disrupting the gradient required for immune cells to reach the inflamed site, while reducing the likelihood of severe adverse events.
After 12 weeks of treatment, the researchers found that clinical remission occurred in 24% and 28% of participants receiving 30 mg and 60 mg of tamuzimod, respectively, compared to an 11% remission rate in the placebo group. These benefits were evident through symptomatic, endoscopic, and histological improvements. While tamuzimod use was associated with an increased incidence of upper respiratory tract infections and led to treatment discontinuation in about 5% of participants, adverse events such as bradycardia or atrioventricular block—often associated with other S1PR modulators—were not observed.
The phase 2 clinical trial enrolled 213 individuals, averaging 40.6 years of age, each with at least a 3-month history of ulcerative colitis. Using the modified Mayo Score, which has a maximum severity of 12, the cohort’s average baseline score was approximately 6.7. About 80% of participants were concurrently treated with aminosalicylic acid, and around 25% received corticosteroids. Patients were randomly assigned to receive a 12-week course of either placebo or tamuzimod at two dose levels—60 mg or 30 mg. Tamuzimod specifically targets the S1PR1 variant, with minimal interaction with S1PR2 and S1PR3, thereby disrupting the gradient required for immune cells to reach the inflamed site, while reducing the likelihood of severe adverse events.
After 12 weeks of treatment, the researchers found that clinical remission occurred in 24% and 28% of participants receiving 30 mg and 60 mg of tamuzimod, respectively, compared to an 11% remission rate in the placebo group. These benefits were evident through symptomatic, endoscopic, and histological improvements. While tamuzimod use was associated with an increased incidence of upper respiratory tract infections and led to treatment discontinuation in about 5% of participants, adverse events such as bradycardia or atrioventricular block—often associated with other S1PR modulators—were not observed.