Biologics, glucocorticoids present 'real problem' for managing infection risk
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While glucocorticoids are a “real problem” in causing infections among patients with rheumatic and autoimmune diseases, complications linked to biologics should be on the radar for rheumatologists as well, according to a speaker here.
After reviewing the most common infections occurring with biologic therapies — from non-serious upper respiratory infections to tuberculosis (TB) and hepatitis B — Cassandra Calabrese, DO, of the department of rheumatologic and immunologic disease at the Cleveland Clinic, discussed the prevalence of infections with attendees at the Basic and Clinical Immunology for the Busy Clinician symposium.
“We are all familiar with the events,” she said. “As you can see, the range is between three and six serious infections per 100 patient-years, depending on which biologic you are looking at.”
Age, history of serious infections and other comorbidities should be assessed when creating an infection risk profile for any patient, but there is one culprit that should not be ignored.
“You can’t have this conversation without understanding that glucocorticoids are a real problem,” Calabrese said. “They are an independent predictor of infection in patients treated with TNF inhibitors and other biologics.”
Looking at specific events, Calabrese suggested that hepatitis B reactivation has become an increasing issue over the last decade. Rituximab (Rituxan, Genentech) may be implicated, along with TNF inhibitors and – while limited data are available – tocilizumab (Actemra, Genentech) and abatacept (Orencia, Bristol Myers Squibb) have also shown evidence that this risk is elevated.
Calabrese noted that forthcoming American College of Rheumatology guidelines will offer updated information on HBV screening. At the moment, monitoring for this complication is conditionally recommended.
Latent TB is another serious risk for rheumatology patients, according to Calabrese, who suggested that patients with latent, or asymptomatic, infection may carry a 5% to 10% risk of developing TB. “You should assess for and discuss this risk at every visit, and limit glucocorticoid exposure,” Calabrese said.
A tuberculin skin test or interferon- release assay (IGRA) are the two ways of assessing for TB, according to Calabrese. The 2015 ACR guidelines suggest screening with one of these methods prior to biologic or tofacitinib (Xeljanz, Pfizer) initiation, while the 2017 American Tuberculosis Society/Infectious Diseases Society of America guidelines suggest that IGRA is preferred over tuberculin skin test.
After treatment, repeat screening should only occur if the patient has visited an endemic area or shows signs and symptoms of TB. “Repeating the test yearly will only run you into trouble in low endemic countries,” Calabrese said.
Another complication that should be on the radar of clinicians in the U.S. is the risk of histoplasmosis with TNF inhibitors. It is a significant concern domestically because “histoplasmosis is endemic to the U.S., and TB is not,” Calabrese said. “It is important to educate our patients about this as a risk, which entails inquiring about travel, symptoms and anything that resembles a pneumonia.”
Despite these concerns, recent retrospective data showed that there is hope for ongoing TNF inhibitor use even in the setting of histoplasmosis. “You can rechallenge a patient with a TNF inhibitor that has been previously diagnosed with histoplasmosis as long as their infection has been treated and is resolved,” Calabrese said.
The final complication Calabrese discussed was coccidiomycosis, which she described as a “primary pulmonary infection caused by inhalation of arthroconidia.”
There is one key risk factor that clinicians should be aware of for coccidiomycosis. “Immunosuppression clearly increases this risk,” Calabrese said.
It is with all of this in mind that Calabrese offered one final point for rheumatologists to consider. “Assess for and discuss infection risk at every visit with every patient,” she said.
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Calabrese C. Infectious Complications of Biologic Therapy. Presented at Basic and Clinical Immunology for the Busy Clinician; Feb. 5-6, 2021. (virtual meeting).
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