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Steroid use in polymyalgia, GCA linked to significantly higher infection risk
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The use of oral steroids in patients with polymyalgia rheumatica or giant cell arteritis is associated with a significant increase in the risk for infection, with higher doses linked with higher risks, according to recent findings published in the Canadian Medical Association Journal.
“Polymyalgia rheumatica and giant cell arteritis are two common rheumatological diseases of older people,” Mar Pujades-Rodriguez, PhD, MSc, of the University of Leeds in England, told Healio Rheumatology. “They are treated with medium-to-high doses of oral steroids — for example, up to 15 mg of prednisolone for polymyalgia rheumatica and up to 60 mg for giant cell arteritis — for 6 months to several years. Steroids are effective in reducing inflammation and disease symptoms, but they also reduce the ability of the immune system to fight infections.”
She added, “Doctors and scientists know that steroids increase the risk of infection, but no one has successfully quantified this risk in a way that is useful to patients, clinicians and decision makers.”
To analyze the dose-response risk for infection among patients in England with polymyalgia rheumatica or giant cell arteritis, Pujades-Rodriguez and colleagues conducted a retrospective record-linkage study of adults seen at family practices that participate in the Clinical Research Datalink. Specifically, patients with prevalent and incident polymyalgia rheumatica or giant cell arteritis who consented to data linkage to hospital databases, and who were registered in their family practice in England for at least 1 year between Jan. 1, 1997, and March 15, 2017, were included in the study.
The researchers analyzed data on 39,938 patients from 389 family practices. The researchers obtained estimates of first occurring infection per level of time-variant current and cumulative steroid dose using Kaplan-Meier methods, as well as multilevel, proportional-hazards Cox models. The primary outcome was the first occurrence of all-cause infection.
According to the researchers, 55.7% of included patients experienced at least one infection over a median follow-up period of 4.8 years, with 26.7% requiring hospital admission and 7.3% dying within 7 days of diagnosis. The cumulative risks for all-cause infection were 18.3% (95% CI, 17.9-18.7) at 1 year, 54.7% (95% CI, 54.1-55.2) at 5 years and 76.9% (95% CI, 76.2-77.5) at 10 years.
The most common cases were lower respiratory tract infections, conjunctivitis and herpes zoster.
The adjusted HR for all-cause infection per increase in 5-mg prednisolone equivalent daily dose was 1.13 (95% CI, 1.12-1.14). For 1,000-mg cumulative dose increases in the last year from the end of follow-up, the increase was 1.5 (95% CI, 1.49-1.52). In addition, the researchers noted stepwise dose-related links for bacterial, viral, parasitic and fungal infections, regardless of patient age, duration of underlying chronic disease and baseline vaccination status.
“Patients with polymyalgia rheumatica and giant cell arteritis and clinicians should be educated about the risk of infection, need for symptom identification, prompt treatment, timely vaccination and documentation of history of chronic infections, such as herpes zoster,” Pujades-Rodriguez said.
“The management of infections has major cost and workload implications for the health care system,” she added. “The estimated risks of dose-response associated with steroids can be useful for clinicians and policymakers to guide the introduction of alternative drugs and improve outcomes of patients with these rheumatological diseases. For example, conducting benefit-harm assessments of newly licensed steroid-sparing drugs that could be recommended instead of oral steroids.” – by Jason Laday
Disclosures: Pujades-Rodriguez reports no relevant financial disclosures. Please see the full study for additional researchers’ disclosures.
Perspective
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David A. McLain, MD, FACP, FACR
This is a very large database study – almost 40,000 patients in almost 400 clinics over the course of 20 years – looking at the infection risk of oral glucocorticoids prescribed in primary care clinics in England for polymyalgia rheumatica and giant cell arteritis.
This retrospective database investigation searched for infection using ICD codes and the types of infections were subdivided into bacterial, fungal (mostly Candida), viral (mostly herpes zoster, influenza, and viral hepatitis) and parasitic (no specifics on which parasites).
Of the more than 22,000 patients with at least one infection, 27% required hospital admission and 7% died within 7 days. The average age of this was cohort was 73 years old. The cumulative risk of infection at 10 years was 76.9%. This data analysis found an association between all doses of oral glucocorticoids and infection, even the 0-4.9 mg of prednisolone equivalent. Prednisone is the inactive form of prednisolone and they have equal potency in contrast to methylprednisolone, which is 20% stronger.
The risk of infection was higher during use than non-use of glucocorticoids. Moreover, the risk of infection increased with increasing doses of prednisolone equivalent, as might be expected.
At one year, the risk of all-cause infection was 13% in non-users, 18% in those receiving the prednisolone equivalent below 5 mg per day, and 36% in those on prednisolone over 25 mg per day. The researchers found that older patients had a higher cumulative probability of all cause and bacterial infections.
Interestingly, patients who were vaccinated (mostly for influenza, zoster, and pneumococcal) were at higher risk for all types of infections than those who were not vaccinated – perhaps higher risk patients, such as those with asthma, COPD and diabetes, were more likely to be vaccinated.
In addition, patients who were prescribed non-oral glucocorticoids (nasal, intramuscular, rectal, topical) had a higher risk for all types of infections than those not treated with non-oral glucocorticoids. There is a tremendous amount of data here to analyze, but according to their analysis, there is an increased risk of infection with even very low doses of glucocorticoids in elderly patients with polymyalgia rheumatica and giant cell arteritis.
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