Prophylaxis in Vasculitis Cuts Risk for Non-PJP Infections

Medscape

12-05-2025

Prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMX) significantly reduced the risk for serious infections by approximately 50% in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, with the greatest benefits observed during the first 180 days of treatment.
METHODOLOGY:
Researchers conducted an observational study that used a target trial emulation framework to examine the effect of prophylactic TMP-SMX on the incidence of serious infections in patients with ANCA-associated vasculitis.
They included 296 patients with new-onset or relapsing ANCA-associated vasculitis from four tertiary referral hospitals in South Korea who received either rituximab or cyclophosphamide as induction therapy between 2005 and 2023.
Of these, 240 patients received TMP-SMX prophylaxis (prophylaxis group; mean age, 63.7 years; 55.8% women) within 14 days of induction therapy, and 56 patients did not receive prophylaxis (control group; mean age, 61.5 years; 60.7% women) during the same period.
Physicians at each institution determined patient eligibility for prophylactic TMP-SMX, with dosage being either one single-strength tablet (TMP 80 mg and SMX 400 mg) daily or one double-strength tablet (TMP 160 mg and SMX 800 mg) every other day, adjusted for renal function.
The primary outcome was the incidence of serious infections requiring intravenous antimicrobial treatment, hospitalization, or extended hospital stay. Secondary outcomes included infection-related deaths and severe adverse drug reactions related to TMP-SMX.
TAKEAWAY:
Approximately 45.8% of patients discontinued the use of prophylactic TMP-SMX within the first 180 days. During 252.1 person-years of observation, 77 serious infections occurred in 65 patients, with an incidence rate of 30.5 per 100 person-years and a fatality rate of 18.5%. Most serious infections (85.7%) occurred within the first 180 days of observation (incidence rate ratio, 5.43; 95% CI, 2.87-10.28).
The prophylaxis group had a significantly lower 1-year incidence than the control group (hazard ratio [HR], 0.48; 95% CI, 0.32-0.72), particularly during the first 180 days (HR, 0.41; 95% CI, 0.22-0.76) but not thereafter (HR, 3.76; 95% CI, 0.46-29.43).
Infection-related mortality was also significantly lower in the prophylaxis group than in the control group (HR, 0.23; 95% CI, 0.10-0.53).
Over 127.4 person-years of TMP-SMX prophylaxis, 35 cases of adverse events occurred, eight of which were adverse drug reactions related to prophylactic TMP-SMX, and 27 patients discontinued TMP-SMX. Only one case of severe adverse drug reaction was noted, which was resolved after treatment discontinuation.
IN PRACTICE:
'Our results strongly suggest that prophylactic TMP-SMX provides additional benefits in patients with AAV [ANCA-associated vasculitis] beyond reducing the risk of PJP [ Pneumocystis jirovecii pneumonia],' the authors wrote.
SOURCE:
This study was led by Yun Kyu Kim, MD, Seoul National University College of Medicine, Seoul, Republic of Korea, and was published online on April 14, 2025, in Arthritis & Rheumatology .
LIMITATIONS:
Unmeasured confounders, such as compliance with prophylactic TMP-SMX, may have influenced the findings. The varied duration of TMP-SMX use in the prophylaxis group, with many patients discontinuing within 180 days, may have led to biased estimates. Additionally, the impact of TMP-SMX on COVID-19 incidence and related infectious complications could not be estimated for patients with an index date prior to 2018.
DISCLOSURES:
This study was supported by a grant from the National Research Foundation of Korea. One author reported receiving salary from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported receiving grants and consulting fees from various pharmaceutical companies.