Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the large intestine. In October 2023, the FDA approved a new treatment option for adults with moderately to severely active UC: etrasimod, marketed under the brand name Velsipty (Pfizer). This approval marks a significant step forward in UC management, offering a potential alternative for patients who haven’t responded to or tolerated other treatments. This article will delve into the clinical trials, mechanism of action, and benefits of etrasimod, offering insights from both a pharmacist and physician perspective.
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Understanding Etrasimod and its Mechanism of Action
Etrasimod is a selective sphingosine 1-phosphate (S1P) receptor modulator. It specifically targets S1P1, S1P4, and S1P5 receptors, playing a crucial role in regulating lymphocyte trafficking. By partially and temporarily inhibiting lymphocytes from leaving lymphoid organs, etrasimod reduces their numbers in the peripheral blood. This mechanism is believed to lessen lymphocyte migration into the intestines, mitigating inflammation in the gastrointestinal tract, a hallmark of UC. While the exact mechanism of etrasimod’s therapeutic effect in UC isn’t fully understood, this reduction in intestinal lymphocyte infiltration is likely a key contributor.
Clinical Trial Results: The ELEVATE UC Program
The FDA approval of etrasimod was based on positive results from Pfizer’s ELEVATE UC phase 3 program, which included two clinical trials: ELEVATE UC 52 and ELEVATE UC 12. These trials involved adults with moderately to severely active UC who hadn’t responded adequately to or couldn’t tolerate at least one other approved UC treatment. Participants were randomly assigned to receive either 2 mg of etrasimod daily or a placebo.
In ELEVATE UC 52, etrasimod demonstrated significantly higher clinical remission rates compared to placebo, both after 12 weeks (27% vs. 7%) and at week 52 (32% vs. 7%). ELEVATE UC 12 showed similar results, with 25% of the etrasimod group achieving clinical remission after 12 weeks compared to 15% of the placebo group.
Safety and Tolerability of Etrasimod
While generally well-tolerated, etrasimod did have some reported adverse events. However, the incidence of adverse events was comparable between the etrasimod and placebo groups in both trials. Importantly, no deaths or malignancies were reported. Common side effects included headache, fatigue, and nasopharyngitis.
Etrasimod: A Pharmacist’s Perspective on Dosage and Administration
Etrasimod offers a simplified dosing regimen compared to some other S1P receptor modulators. Unlike ozanimod (Zeposia), which requires titration, etrasimod is administered as a consistent 2 mg daily dose. This straightforward dosing can improve patient adherence and simplify treatment management.
A Physician’s Perspective on Etrasimod’s Role in UC Treatment
Etrasimod offers a valuable new oral therapeutic option for UC, addressing a significant unmet need for patients seeking alternatives to parenteral therapies or treatments with a higher risk of serious side effects. It offers the potential for clinical remission without reliance on steroids, which are typically used for short-term management of flares. However, like all medications, etrasimod has potential side effects. It’s important to be aware of the possibility of temporary reductions in heart rate and atrioventricular conduction at the beginning of treatment. Patients with certain cardiovascular conditions are contraindicated from using etrasimod. As with any new medication, a physician should carefully evaluate a patient’s medical history and current health status before prescribing etrasimod.
Conclusion: A Promising New Option for UC
Etrasimod (Velsipty) offers a promising new approach for managing moderately to severely active ulcerative colitis. Its effectiveness in inducing and maintaining clinical remission, combined with a convenient oral administration and generally favorable safety profile, makes it a valuable addition to the treatment landscape. For personalized treatment plans and further information, consult with a healthcare professional.
References
U.S. FDA Approves Pfizer’s VELSIPITY for Adults with Moderately to Severely Active Ulcerative Colitis (UC). https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-velsipitytm-adults-moderately. Accessed October 19, 2023.
Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet. 2023. doi:https://doi.org/10.1016/S0140-6736(23)00061-2
Al-Shamma H, Lehmann-Bruinsma K, Carroll C, et al. The Selective Sphingosine 1-Phosphate Receptor Modulator Etrasimod Regulates Lymphocyte Trafficking and Alleviates Experimental Colitis. J Pharmacol Exp Ther. 2019 Jun;369(3):311-317. doi: 10.1124/jpet.118.254268.
Velsipty (etrasimod). [prescribing information]. New York, NC: Pfizer, Inc.; October 2023.
