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.

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/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/