POS0234 IMPACT OF PROPHYLACTIC TRIMETHOPRIM-SULFAMETHOXAZOLE ON THE INCIDENCE OF SERIOUS INFECTION IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS: A MULTICENTER COHORT STUDY
Authors: J. W. Park, Y. K. Kim, J. R. Curtis, S. R. Choi, J. N. Yeo, M. J. Kim, Y. J. Lee, E. B. Lee
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Infection is a major cause of mortality within the first year of induction therapy in patients with ANCA-associated vasculitis (AAV). A recent EULAR AAV guideline recommends the prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX) against Pneumocystis jirovecii pneumonia (PJP) and other infections. However, while a limited number of studies have suggested an association between prophylactic TMP-SMX and lower incidence of serious infections, this relationship has not been thoroughly investigated in a large-scale real-world cohort. <h3>Objectives:</h3> We aimed to investigate the impact of TMP-SMX in preventing serious infection in patients with AAV receiving either rituximab (RTX) or cyclophosphamide (CYC). <h3>Methods:</h3> This multicenter cohort study included patients with AAV treated with either RTX or CYC for induction therapy in three referral hospitals in South Korea. A total of 280 patients were analyzed. The date when RTX or CYC was administered was set as the index date. Then, the patients were divided into TMP-SMX group (n=230) and control group (n=50) according to whether they received TMP-SMX during 28 days from the index date, which was set as a lead-in period. Primary outcome of this study was 1-year incidence of serious infections, which was defined as requiring IV antibiotic treatment, hospitalization or prolongation of hospitalization. The hazard ratio of serious infection was estimated using Cox proportional hazard model. Additionally, the impact of prophylaxis was also analyzed stratified by various clinical factors. <h3>Results:</h3> Over 209.8 person-years in the entire cohort, 60 serious infections occurred, with a 1-year mortality rate of 18.3%. The incidence rate of serious infection (per 100 person-years) was 26.2 and 42.7 in the TMP-SMX group and the control group, respectively. The most common source of infection was respiratory tract (n = 31, 51.7%), followed by gastrointestinal (n = 8, 13.3%) and genitourinary tract (n = 8, 13.3%). There were 4 PJP cases, 1 in the TMP-SMX group and 3 in the control group. Most serious infections (68.3%) occurred during the first 90 days. Overall, prophylactic TMP-SMX significantly reduced the incidence of serious infections (adjusted hazard ratio (HR) 0.39 [0.28-0.54]). Time-varying Cox regression showed that the benefit of prophylactic TMP-SMX was evident during the first 90-day period (adjusted HR 0.32 [0.24-0.44]) but was not significant afterward (Figure 1). The prophylactic impact of TMP-SMX was also significant in serious infection except PJP and viral infection (adjusted HR 0.59 [0.39-0.91]). In the subgroup analysis, the impact of prophylactic TMP-SMX was more prominent in the presence of baseline lymphopenia (defined as lymphocyte count &lt; 800/µL), azotemia (defined as estimated GFR &lt; 60mL/min/1.73m2), or in patients with microscopic polyangiitis. Other clinical factors such as patient's age, baseline BVAS, lung involvement, and concomitant steroid pulse treatment did not show a significant interaction with the effect of TMP-SMX (Figure 2). <h3>Conclusion:</h3> Prophylactic TMP-SMX significantly reduces the 1-year incidence of serious infection in patients with AAV undergoing induction therapy with CYC or RTX. However, this additional benefit is evident primarily during the initial period following induction therapy. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>