1830: Adverse Drug Reactions to Trimethoprim-sulfamethoxazole as a Prophylactic Agent Against Pneumocystis Pneumonia in Patients with Systemic Lupus Erythematosus: anti-Sm Antibody as a Possible Risk Factor
Shinji Izuka1, Hiroyuki Yamashita2, Yuko Takahashi2 and Hiroshi Kaneko2, 1Devision of Rheumatic Disease, National Center for Global Health and Medicine, Toshima-Ku, Tokyo, Japan, 2Devision of Rheumatic Disease, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan
Background/Purpose: Pneumocystis pneumonia (PCP) is a life-threatening infection in immunocompromised patients, including those with connective tissue diseases (CTDs), treated with corticosteroids or immunosuppressive agents. Trimethoprim-sulfamethoxazole (TMP-STX) is widely used as a prophylactic agent against PCP. Although its efficacy is well-established, TMP-STX may cause adverse drug reactions (ADRs) among patients with CTDs. Previous studies showed that patients with systemic lupus erythematosus (SLE) are at high-risk of ADRs to TMP-SMX, but the prevalence varies among studies and the difference in risks between patients with SLE versus other CTDs is unclear. We examined the prevalence of ADRs to TMP-STX among patients with SLE and other CTDs, and identified specific risk factors for ADRs in SLE. Methods: The in-patient database of our hospital was examined, and the records of CTD patients administered TMP-STX as a prophylactic agent against PCP between January 2009 and April 2020 were reviewed retrospectively. Baseline data were obtained at the time of TMP-STX initiation. Patients with human immunodeficiency virus, and those who did not suffer ADRs but who received TMP-SMX within 1 month, were excluded. ADR prevalence was compared between SLE patients and those with other CTDs. Univariate and multivariate analyses were conducted to identify the risk factors for ADRs in SLE patients
. Results: Among 427 patients with CTDs (SLE, n = 164; polymyositis or dermatomyositis, n = 83; Sjögren syndrome, n = 25; systemic sclerosis, n = 22; mixed connective tissue disease, n = 11; eosinophilic granulomatosis with polyangiitis, n = 17; granulomatosis with polyangiitis, n = 22; microscopic polyangiitis, n = 46; polyarteritis nodosa, n = 10; Takayasu arteritis, n = 7; giant cell arteritis, n = 20), 40 patients (9.4%) developed ADRs (thrombocytopenia, n = 10; skin rash, n = 9; liver function test abnormality, n = 7; fever, n = 7; others, n = 12). The prevalence of ADRs in SLE patients was 13.4% and 6.9% in control group. The odds ratio (OR) of an ADR for SLE patients was 2.12 (95% confidence interval (CI) 1.05–4.35, p=0.037). By contrast, the ORs of ADRs for all other CTDs did not differ significantly. Univariate analyses of SLE patients revealed that positivity for anti-Sm antibody (OR 5.44, 95% CI 1.93–16.06, p< 0.001), anti-RNP antibody (OR 3.19, 95% CI 1.11–10.02, p = 0.018) and anti-Ro/SS-A antibody (OR 2.87, 95% CI 1.06–7.77, p = 0.039) was significantly associated with ADRs. In the multivariate analyses, only anti-Sm antibody was significantly associated with ADRs in SLE patients (OR 3.34, 95% CI 1.10–11.10, p = 0.048). Conclusion: SLE patients prophylactically administered TMP-STX are at high risk of ADRs. In particular, anti-Sm antibody positivity was significantly associated with ADR. SLE patients showing anti-Sm antibody, anti-RNP antibody, or anti-Ro/SS-A antibody positivity who receive prophylactic TMP-SMX should be especially carefully monitored for ADRs.