Antibiotic mix may prevent serious infections with rituximab for GPA
Immunosuppressant can lower response against bacteria, increase infection risk
The combination antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) may help prevent serious infections for people with granulomatosis with polyangiitis (GPA) who are taking the immunosuppressant rituximab, a study of U.S. data shows.
Preventive treatment, or prophylaxis, with TMP-SMX in people with this common type of ANCA-associated vasculitis (AAV) tended to increase the likelihood of adverse events, however.
“Trimethoprim-sulfamethoxazole was associated with reduced serious infections, but was potentially associated with adverse events,” the researchers wrote. “Future research should assess how to balance benefits and harms of prophylaxis in individual patients.”
The study, “Trimethoprim sulfamethoxazole prophylaxis and serious infections in granulomatosis with polyangiitis treated with rituximab,” was published in Rheumatology.
In AAV, a self-directed immune response causes small blood vessels to become inflamed, leading to organ damage. GPA mainly affects the lungs, the kidneys, and the upper respiratory tract, such as the nose and ears.
Rituximab, sold as Rituxan among other brands and available as biosimilars, is approved to induce and maintain disease remission in adults with GPA or microscopic polyangiitis, another type of AAV. Administered into the bloodstream, it promotes the death of B-cells, the immune cells that produce antibodies, including those involved in the self-reactive immune response that drives AAV.
Because it weakens the immune system, rituximab can tamp down the natural response against harmful bacteria, increasing the risk of serious infections. To prevent these, doctors can prescribe prophylaxis with antibiotics, including the TMP/SMX combination, which is used to kill certain bacteria and fungi that can cause serious pneumonia.
Can TMP-SMX cut rituximab infection risk in GPA?
To see if TMP-SMX prophylaxis could help prevent serious infections in GPA patients, researchers in Canada searched a U.S. health database to identify insured adults with GPA who’d 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. Just over half (52%) were women, and most (74%) had received induction treatment with rituximab. Nearly one-third (31%) were prescribed TMP-SMX prophylaxis for a median of about 4.5 months.
TMP-SMX treatment was considered prophylactic if the patient had a prescription for at least 28 days, starting around the time as their first rituximab treatment.
The researchers then looked at the occurrence of serious infections, or those that required hospitalization, with viral infections being excluded, as these wouldn’t be expected to be prevented by TMP-SMX.
Over a median follow-up of nearly 1.5 years, 104 patients (11%) had 130 serious infections. The most frequent were respiratory (36%) and bacteremia, or general sepsis (45%), which refers to bacteria in the bloodstream and a life-threatening immune reaction against a serious infection.
Statistical models adjusted for potential influencing factors showed TMP-SMX was significantly associated with a 50% lower risk of serious infections. In turn, a previous hospitalization was significantly linked to a 79% higher risk of serious infections. Prior serious infection and having more than one simultaneous health condition were each significantly associated with a twofold higher chance of serious infection.
Further analyses suggested the combination’s effects were generally similar across sexes and between patients younger than 50, and those older. But the effect appeared to be even greater among those on a daily dose of prednisone, a glucocorticoid, of at least 20 mg, with TMP-SMX treatment being linked to a 76% reduced risk of serious infection.
Moreover, TMP-SMX prophylaxis wasn’t significantly associated with a reduced risk of infections treated in outpatient settings. The combination therapy tended to be linked to a reduced chance of Pneumocystis jirovecii pneumonia, a type of lung infection that TMP-SMX is meant specifically to prevent, but this didn’t 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 link wasn’t statistically significant.
The findings showed “TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies,” the researchers wrote.
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