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Arthritis Rheumatol., Apr 14 2025, | https://doi.org/10.1002/art.43185
Time-dependent effect of prophylactic trimethoprim-sulfamethoxazole on the incidence of serious infections in ANCA-associated vasculitis: A target trial emulation study
Yun Kyu Kim 1, Jeffrey R Curtis 2, Se Rim Choi 3, Jina Yeo 4, Min Jung Kim 5, Yun Jong Lee 1,3, Eun Bong Lee 1,6, Jun Won Park 1
1Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
3Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
4Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
5Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government - Seoul National University, Boramae Medical Center, Seoul, Republic of Korea.
6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Corresponding Author : Jun Won Park MD
1Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
3Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
4Division of Rheumatology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
5Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government - Seoul National University, Boramae Medical Center, Seoul, Republic of Korea.
6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Corresponding Author : Jun Won Park MD
Abstract
Objectives: To investigate the effect of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) on the incidence of serious infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).
Methods: This multicenter cohort study designed to emulate a target trial studied 296 patients with AAV treated with rituximab or cyclophosphamide as induction therapy. Patients were grouped based on the administration of TMP-SMX within 14 days following induction therapy (n=240 and 56 patients in prophylaxis and control groups, respectively) (intention-to-treat) and also as a time-dependent exposure (time-varying). Inverse probability weighting was applied to minimize the baseline imbalance between the two groups. Primary outcome was 1-year incidence of serious infection.
Results: During the 252.1 person-years of observation, 77 cases of serious infections were recorded in 65 patients, with a fatality rate of 18.5%. Most serious infections (n=66, 85.7%) occurred within the first 180 days of observation. The prophylaxis group showed a significantly lower incidence of serious infections than the control group (HR 0.48 [0.32-0.72]). However, this beneficial effect of TMP-SMX was only significant during the first 180 days (HR 0.41 [0.22-0.76]) and not thereafter (HR 3.76 [0.46-29.43]) (interaction p=0.044). This result was also consistent with the time-varying analysis result. Based on one case of severe adverse drug reaction related to TMP-SMX, the number needed to harm was 127.4 whereas the number needed to treat to prevent one serious infection was 8.0.
Conclusion: Prophylactic TMP-SMX significantly reduced the risk of serious infections in patients with AAV, particularly during the first 6 months of induction therapy with rituximab or cyclophosphamide.
Methods: This multicenter cohort study designed to emulate a target trial studied 296 patients with AAV treated with rituximab or cyclophosphamide as induction therapy. Patients were grouped based on the administration of TMP-SMX within 14 days following induction therapy (n=240 and 56 patients in prophylaxis and control groups, respectively) (intention-to-treat) and also as a time-dependent exposure (time-varying). Inverse probability weighting was applied to minimize the baseline imbalance between the two groups. Primary outcome was 1-year incidence of serious infection.
Results: During the 252.1 person-years of observation, 77 cases of serious infections were recorded in 65 patients, with a fatality rate of 18.5%. Most serious infections (n=66, 85.7%) occurred within the first 180 days of observation. The prophylaxis group showed a significantly lower incidence of serious infections than the control group (HR 0.48 [0.32-0.72]). However, this beneficial effect of TMP-SMX was only significant during the first 180 days (HR 0.41 [0.22-0.76]) and not thereafter (HR 3.76 [0.46-29.43]) (interaction p=0.044). This result was also consistent with the time-varying analysis result. Based on one case of severe adverse drug reaction related to TMP-SMX, the number needed to harm was 127.4 whereas the number needed to treat to prevent one serious infection was 8.0.
Conclusion: Prophylactic TMP-SMX significantly reduced the risk of serious infections in patients with AAV, particularly during the first 6 months of induction therapy with rituximab or cyclophosphamide.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-15)
- 국내(교신)+국외 연구진
- 의약학 > 응용의학
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