Antibiotics Can Help AAV Patients on Rituxan Lower Risk of Severe Infections, Study Finds

Treatment with a common antibiotic reduces the risk of life-threatening infections in ANCA-associated vasculitis patients being given Rituxan (rituximab) for their condition, a study conducted in the U.K. and Austria reports.

This finding supports the use of the antibiotic trimethoprim-sulfamethoxazole in routine clinical practice for these patients.

The study, “Trimethoprim–sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis” was published in the journal Annals of Rheumatic Diseases.

While the prognosis for ANCA-associated vasculitis (AAV) patients has improved, these people are often exposed to serious complications, either as a consequence of the disease itself or as side effects of medicines, particularly immune suppressors.

Severe infections are among the most worrying complications. Around 48 percent of deaths in the first year of treating this disease are caused by infections, which remain among the three leading causes of death thereafter. 

A likelihood of infections increases when the immune system is depressed, and AAV patients taking medicines that suppress the immune system — such as cyclophosphamide and Rituxan – are particularly at risk.

In fact, several studies have warned of multiple life-threatening infections (bacterial, fungal, and viral) following Rituxan treatment. But no clinical recommendations have been issued about the use of prophylactic — preventive — treatments to avoid severe infections in these patients.

For patients receiving cyclophosphamide, the European League Against Rheumatism/European Renal Association – European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommends prophylaxis with an antibiotic. But little is known about infections in AAV patients treated with Rituxan.

Researchers investigated the frequency of severe or life-threatening infections in AAV 192 patients who had been treated with Rituxan. All were referred to either  Addenbrooke’s Hospital (Cambridge, U.K.) or the Medical University Innsbruck (Austria) between 2004 and 2014.

Follow-up began at the time of Rituxan administration and continued for two years. Overall, 95 severe infections were recorded in 49 patients (25.52%).

Importantly, patients who were receiving prophylactic treatment with the antibiotic trimethoprim-sulfamethoxazole (sold as Bactrim, among others) were less prone to severe infections.

In fact, those given the antibiotic — commonly used to treat several bacterial infections, including respiratory tract infections — had a 70% lower chance of developing severe infections.

Use of trimethoprim-sulfamethoxazole also significantly reduced the time to first significant infection.

Patients with signs of vasculitis in their bronchi or with chronic obstructive pulmonary disease (COPD) were two and six times more likely of getting a serious infection, respectively. 

Other significant risk factors were prior treatment with the immunotherapy Lemtrada (alemtuzumab) and, to a lesser extent, patient age.

Respiratory tract infections were the leading cause of severe infections (63 cases), followed by infections of the urinary tract (12 cases), and gastrointestinal tract (8 cases).

The risk of respiratory infections was significantly higher in patients with bronchi involvement, severe bronchiectasis, high neutrophil blood counts, or who were taking Rituxan due to disease relapse.

But those receiving Rituxan after failing to respond to prior treatment (refractory) had a lower frequency of severe infections.

“We found severe infections occurring in approximately one quarter of patients in a 2-year observation period after rituximab therapy” the researchers wrote.

“There was a reduction of severe infections when trimethoprim–sulfamethoxazole prophylaxis was used,” they added, concluding that “while these results require confirmation, they support routine use of trimethoprim–sulfamethoxazole in rituximab-treated patients.”