TMP-SMX prophylaxis reduces PCP incidence during steroid treatment for rheumatic disease
Prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) reduces the incidence of pneumocystis pneumonia (PCP) in patients exposed to prolonged high-dose steroid treatment for rheumatic disease, and has a favourable safety profile, according to a study.
“[Although] systemic high-dose steroid treatment is one of the most important weapons against rheumatic diseases … it is a risk factor for PCP … [Our findings reveal that] TMP-SMX was highly effective at preventing PCP and related mortality,” said the researchers.
A total of 1,522 treatment episodes from 1,092 patients on prolonged (≥4 weeks) high-dose steroid treatment (≥30 mg/day prednisone) were identified. Episodes involved either TMP-SMX (prophylaxis group, n=262) or no prophylaxis (control group, n=1,260). [Ann Rheum Dis 2017;doi:10.1136/annrheumdis-2017-211796]
At baseline, there was a significantly higher proportion of patients with diseases associated with a high PCP risk such as granulomatosis with polyangiitis (GPA, 6.9 percent vs 3 percent; p=0.003) and microscopic polyangiitis (MPA, 4.2 percent vs 0.7 percent; p<0.001) in the prophylaxis vs the control arms. Thirty PCP cases (n=29 and 1 in the control and prophylaxis groups, respectively) were identified during the observation period, with a higher incidence observed among those receiving a higher initial steroid dose (≥60 mg daily, incidence rate ratio, 3.35; p=0.023).
After adjusting for age, GPA, MPA, higher steroid dose, concomitant cyclophosphamide pulse, and baseline lymphopenia, there was a significant reduction in the incidence of PCP (hazard ratio [HR], 0.06; p=0.022) and PCP-related mortality (adjusted HR [adjHR], 0.09; p=0.023) in the prophylaxis vs the control arms.
Subgroup analysis further demonstrated that TMP-SMX given as a primary PCP prophylaxis reduced PCP incidence among those who received a higher steroid dose (adjHR, 0.02).
A total of 36 adverse drug reactions (ADRs) occurred in 32 patients (21.2/100 PY), the most common being elevated serum alanine transaminase levels (>1.5 the upper normal range) and skin rash (3.5/100 PY for both), followed by thrombocytopenia (1.8/100 PY) and hyperkalaemia (1.8/100 PY).
According to the researchers, the lower number needed to treat (NNT) vs number needed to harm (52 vs 131) illustrates “that the benefit of TMP-SMX prophylaxis was greater than the risk of potential harm to the patient”.
Moreover, the lower NTT among those receiving a higher vs lower steroid dose (32 vs 215) further demonstrates the favourable risk-benefit ratio of TMP-SMX. “This result suggests that the initial steroid dose may identify patients who would derive maximum benefit from TMP-SMX prophylaxis,” they added.
PCP is a potentially life-threatening infection in immunocompromised patients and has been the most common cause of death in patients with HIV. [N Engl J Med 2004;350:2487-2498; Emerg Infect Dis 2004;10:1713-1720] While effective HIV prophylactic strategies has led to its reduced incidence, PCP remains a significant cause of pneumonia among non-HIV immunocompromised individuals and is associated with more severe manifestations and a higher mortality rate compared with HIV-infected individuals. [Chest 2000;118:704-711; Mayo Clin Proc 1996;71:5-13; Clin Infect Dis 2002;34:1098-1107] “The most important risk factor for PCP in non-HIV patients is the use of immunosuppressive drugs, especially corticosteroids,” said the researchers.
Furthermore, prolonged high-dose steroid treatment is a significant risk factor for PCP in patients with rheumatic diseases; however, there has been no consensus on PCP prophylaxis in this setting, added the researchers.
“[Our findings] may impact the use of PCP prophylaxis for patients with rheumatic diseases,” concluded the researchers, who called for larger randomized trials to further validate the results and obtain an accurate risk-benefit assessment for this patient group.