A recently published prospective observational cohort study from the British Society for Rheumatology Biologics Registry found the rate of tuberculosis among RA patients on biologic therapy plummeted from 783 cases per 100,000 patient-years in 2002 to 38 cases per 100,000 patient-years in 2015.2 Non-tuberculosis opportunistic infections were found at a rate of 134 per 100,000 patient-years. Researchers saw no differences in the overall rate of opportunistic infection between biologic drug classes, which included rituximab, anti-TNF and anti-IL6 therapies.
But the study also points to the ongoing risk of severe infection. Researchers found 5.51 such infections per 100 person-years. The 30-day risk of serious infection leading to mortality in RA was 10%.
Other work has highlighted the infection risk posed by steroids. A 2017 study found that low-dose steroids (7.5 mg or lower) resulted in 6.4 hospitalized infectious events compared with more than double—13.3 events—for high-dose steroids (over 7.5 mg).3
“Steroids clearly impact mortality associated with infection in RA patients,” Dr. Lortholary said.
RA patients also face an increased risk of herpes zoster and herpes zoster-related stroke, with infected RA patients at 27% increased risk, according to a 2017 study.4 But studies have yielded mixed results on whether anti-TNF drugs contribute to the risk of zoster infection, Dr. Lortholary noted.
Researchers have tried to pinpoint factors that may put patients at risk of serious infections on biologics. In a French registry study of 1,491 patients, REGATE, every 10 years of additional age heightened the risk of serious infection by 14% in RA patients treated with anti-IL6 agent tocilizumab. Other significant predictors included treatment in combination with leflunomide. The incidence of 4.7 serious infections per 100 patient-years compared with about four that have been seen with abatacept, five with rituximab and three to six seen with anti-TNF agents, Dr. Lortholary said.5
Prevention
Preventing infection in patients on biologic therapy can be as straightforward as avoiding common hazards, such as pets and exposure on the job, he said. If they smoke, patients should stop to reduce their risk of respiratory tract infections.
Of course, vaccinations are helpful, but can be blunted by biologics. Rituximab can reduce the efficacy of the flu vaccine, and the vaccine also provides less protection in patients on abatacept, he said.
Dr. Lortholary said he hoped for a better team approach between infectious disease experts and rheumatologists in tackling infections in RA.
“We have to face an increasing number of therapeutic families and indications, so be aware that it’s really a challenge for us to follow all these different directions,” he said. “I hope we develop guidance and more collaboration with rheumatologists with these patients treated with biologics.”
