The combination antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) may help prevent serious infections in people with granulomatosis with polyangiitis (GPA) taking the immunosuppressant drug rituximab, a study of US data shows.
However, prophylaxis, or prophylaxis, with TMP-SMX in people with this common type of ANCA-associated vasculitis (AAV) tended to increase the chance of side effects.
“Trimethoprim-sulfamethoxazole was associated with less severe infections, but was potentially associated with adverse events,” the researchers wrote. “Future studies should evaluate how to balance the benefits and harms of prophylaxis in individual patients.”
The study, “Trimethoprim sulfamethoxazole prophylaxis and severe infections in granulomatosis with polyangiitis treated with rituximab” was published in Rheumatology.
In AAV, the autoimmune response causes small blood vessels to swell, leading to organ damage. GPA mainly affects the lungs, kidneys and upper respiratory tract, such as the nose and ears.
Rituximab, sold as Rituxan among other brand names and available as biosimilars, is approved to induce and maintain remission in adults with GPA or microscopic polyangiitis, another type of AAV. Administered into the bloodstream, it promotes the death of B cells, immune cells that produce antibodies, including those involved in the autoimmune response that drives AAV.
Because it weakens the immune system, rituximab can reduce the natural response to harmful bacteria, increasing the risk of serious infections. To prevent this, doctors may prescribe antibiotic prophylaxis, including the TMP/SMX combination, which is used to kill certain bacteria and fungi that can cause severe pneumonia.
Can TMP-SMX reduce the risk of rituximab infection in GPA?
To see if prophylaxis with TMP-SMX could help prevent serious infections in GPA patients, researchers in Canada searched US health databases to identify insured adults with GPA who had been treated with rituximab and had at least six months of medical records. A total of 919 patients, mean age 52.1, met the criteria. Roughly half (52%) were women and most (74%) had received induction treatment with rituximab. Almost a third (31%) were prescribed TMP-SMX prophylaxis for a median of 4.5 months.
TMP-SMX treatment was considered preventive if the patient had a prescription for at least 28 days and started around the time of the first rituximab treatment.
The researchers then looked at the incidence of serious infections, or those requiring hospitalization, excluding viral infections, as TMP-SMX would not be expected to prevent them.
During a median follow-up of nearly 1.5 years, 104 patients (11%) had 130 serious infections. The most common were respiratory (36%) and bacteremia, or systemic sepsis (45%), which refers to bacteria in the bloodstream and a life-threatening immune response to a serious infection.
Statistical models, adjusted for potential confounders, showed that TMP-SMX was significantly associated with a 50% reduced risk of serious infections. In contrast, prior hospitalization was significantly associated with a 79% higher risk of serious infections. A previous serious infection and having more than one health condition at the same time were each significantly associated with twice the odds of a serious infection.
Further analyzes indicated that the effects of the combination were generally similar between genders and between patients younger than 50 and those older. But the effect appeared to be even greater among those receiving a daily dose of prednisone, a glucocorticoid, of at least 20 mg, with TMP-SMX treatment associated with a 76% lower risk of serious infection.
In addition, TMP-SMX prophylaxis was not significantly associated with a lower risk of outpatient-treated infections. Combination therapy tended to be associated with a lower likelihood of Pneumocystis jirovecii pneumonia, a type of lung infection that TMP-SMX is specifically designed to prevent, but this did not reach statistical significance.
Among those prescribed TMP-SMX, 180 (64%) visited the hospital for adverse events possibly related to the combination. Most (88%) involved outpatient visits, and more than half of these adverse events (58%) were due to acute kidney injury.
TMP-SMX prophylaxis tended to be associated with a higher risk of adverse events, but this association was not statistically significant.
The results showed “TMP-SMX prophylaxis was associated with fewer serious infections in rituximab-treated GPA, but may increase adverse events, warranting further investigation into optimal prophylaxis strategies,” the researchers wrote.
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