(P053) INFECTION RATES IN PATIENTS WITH ULCERATIVE COLITIS TREATED WITH A SPHINGOSINE 1-PHOSPHATE RECEPTOR MODULATOR

Background: Ozanimod and etrasimod are oral sphingosine 1-phosphate (S1P) receptor-modulating small molecules approved for the treatment of ulcerative colitis (UC). These therapies prevent migration of lymphocytes from secondary lymphoid organs into the systemic circulation. As expected, and as seen in the registration clinical trials, absolute lymphocyte counts (ALC) fall by a mean of 54% from baseline in patients treated with ozanimod. We aimed to investigate if lymphopenia in patients on S1P receptor modulators was associated with increased risk of infection.

Methods: This was a multi-center retrospective study of adult patients with UC treated with an S1P between July 2021 and September 2024. Patients were identified with ICD-10 code K51.x (UC). Data was abstracted from each patient chart, including demographic information, S1P duration of use, use of concomitant prednisone, presence of lymphopenia defined as an ALC < 500 cells/mm³ after at least 10 weeks of S1P use, and infection while on S1P treatment. If infection was noted while on S1P treatment, data was collected on the type of infection, if the infection required treatment with antimicrobials, and the duration of S1P use up until the time of infection.

Results: A total of 63 patients with UC and S1P receptor modulator use were identified. Average patient age was 46y (standard deviation [SD] 15.9y). The majority (89%) received ozanimod. Average duration of S1P use was 10.4±7.4 months. Thirty-one (49%) patients taking an S1P had lymphopenia. Of the 31 patients with lymphopenia, the average ALC was 330 cells/mm³ (SD 96.1 cells/mm³) and 7 of these patients (23%) had a documented infection with S1P use. Of these 7 patients, the average duration of S1P use at the time of infection was 5±3.4 months. All infections except one upper respiratory infection required treatment with at least one antimicrobial agent, however, none of the infections resulted in hospitalization or S1P discontinuation. In 21 patients with an ALC of 501-1000 cells/mm³, four (19%) developed an infection (all COVID). None of the 11 patients with ALC > 1001 cells/mm³ had a documented infection. There were 22 patients on concomitant prednisone with an S1P; 14 of these patients had lymphopenia. Infection with combination prednisone and S1P use was seen in the 1 patient who had influenza.  No patients developed an opportunistic infection.

Conclusions: Non-life-threatening infections were identified in 11 patients (17%) treated with S1P. All patients with an infection had an ALC < 1000 cells/mm³. Although 17% of our cohort developed an infection, none of the infections were serious enough to merit S1P discontinuation. Further studies are needed to determine risk factors for development of infection in patients prescribed S1P receptor modulators or if there is a difference between ozanimod and etrasimod.