Postdoctoral Researcher Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center Dallas, Texas, United States
Introduction Etrasimod, a selective sphingosine-1-phosphate receptor modulator was approved by the FDA in October 2023 for the treatment of moderately to severely active ulcerative colitis (UC) in adults. An adverse effect of etrasimod is bradycardia. We present the first case of symptomatic bradycardia with a nadir heart rate (HR) less than 40bpm in a patient with moderately severe UC treated on an inpatient basis with etrasimod at a tertiary care facility.
Case Description A 20-year-old female with history of pan-UC diagnosed in 2021 presented with several weeks of abdominal pain, bloody diarrhea, and 1 week of subjective fever and chills. The patient’s disease previously failed to respond to multiple treatments, and she was subsequently admitted for a moderately severe UC flare.
Sigmoidoscopy revealed severe active inflammation (Mayo endoscopic subscore 3). Fecal calprotectin was 2184.5 ug/g, CRP was 77.7 mg/L. The patient’s vitals were stable with an average HR of 80 bpm. She was treated with intravenous corticosteroids (IVCS) for 3 days without improvement. Given the patient’s history of multiple treatment failures, surgical management was offered, however she declined. Subsequently, treatment with etrasimod was planned and started on day 3 of hospitalization. A baseline EKG showed a normal sinus rhythm with no contraindications to initiating therapy [Fig. 1A]. On day 2 of therapy with etrasimod, improvement in stool frequency and consistency was noted with a decrease in CRP to 22.2 mg/L. However, asymptomatic sinus bradycardia with a HR in the mid-high 40s (Range: 44-48 bpm) was reported later that day, and an EKG showed no sign of AV block [Fig. 1B]. HR continued to trend in the low 40s before the patient experienced lightheadedness and chest pressure with a HR nadir of 37 bpm on day 3 of therapy [Fig. 2]. Despite improvement in inflammatory markers and clinical symptoms, etrasimod was discontinued due to the severity of bradycardia with resultant symptoms. Following discontinuation, the patient’s HR returned to baseline within 48 hours, and she continued treatment with IVCS with a planned oral taper. Treatment with upadacitinib was restarted on day 7 of hospitalization, with plans for outpatient dual therapy with vedolizumab. Following further improvement, the patient was discharged on day 8 of hospitalization. Upon follow-up 2 weeks later, the patient experienced a return in her symptoms while awaiting dual therapy and ultimately underwent total abdominal colectomy with end ileostomy 5 weeks thereafter.
Discussion This case of symptomatic bradycardia underscores the need for vigilant cardiovascular monitoring when initiating etrasimod. Physicians should recognize the risk of more pronounced bradycardia than indicated in the full prescribing guide and prioritize ongoing monitoring throughout the course of treatment.
