Extended Glucocorticoids Use Linked to More Infections in Study

People with ANCA-associated vasculitis (AAV) who continue to receive high doses of glucocorticoids for more than six months experience no benefits in terms of survival or relapse rates — but have a much higher risk of infections, a new study suggests.

The results showed these patients have a significantly greater risk of severe infectious complications, such as sepsis and pneumonia, and are more likely to die from infections than individuals who effectively tapered their glucocorticoid doses.

The study, “Glucocorticoid maintenance therapy and severe infectious complications in ANCA-associated vasculitis: a retrospective analysis,” was published in the journal Rheumatology International.

Treatment for severe AAV, an autoimmune disorder that causes blood vessels to swell, involves an initial induction therapy, which aims to control disease and put patients in remission. That is followed by maintenance therapy, designed to keep patients in remission for extended periods.

Glucocorticoids, a type of corticosteroid hormone used to stop damaging inflammation, are currently the standard of care for treating AAV patients. However, their long-term use comes with side effects, including an increased risk of infections, diabetes, heart conditions, osteoporosis, and other disorders.

Limiting the duration of glucocorticoid exposure or tapering such doses over time are believed to result in similar treatment responses but with fewer adverse events. However, the optimal glucocorticoid dosing approach for AAV patients remains to be uncovered.

Now, researchers at the University of Heidelberg, in Germany, investigated the impact of different glucocorticoid maintenance doses on survival, time to relapse, kidney function, irreversible physical damage, and severe infectious complications.

A total of 130 patients — 64 women and 66 men — were included in the analysis. All had been diagnosed with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) between 2004 and 2019 and had been followed for at least one year.

Eligible patients had received cyclophosphamide and glucocorticoids for induction therapy, followed by maintenance therapy with azathioprine or CellCept (mycophenolate mofetil), together with glucocorticoids.

The participants were divided into two groups: those who tapered their glucocorticoid doses as recommended, and were receiving less than 7.5 mg per day six months after initiating their induction therapy, and those who were still receiving doses of 7.5 mg or higher after six months.

A total of 76 patients (58%, mean age 66 years) were included in the first group, while the higher dose group included 54 patients (42%, mean age 65 years). The groups were comparable in terms of sex, age at diagnosis, additional diseases, and AAV subtypes, though those receiving higher doses after six months tended to have a greater disease activity at the time of AAV onset.

The results showed that patients receiving higher glucocorticoid doses after six months had comparable benefits after eight years to those receiving doses lower than 7.5 mg.

In particular, glucocorticoid doses had no impact on patient survival or relapse rates after eight years, or on the time to relapse, or the rates of refractory disease (percentage of patients with unchanged or increased disease activity after three months).

Likewise, kidney function and the proportion of patients with kidney failure were similar in both groups after four years of treatment initiation.

However, infectious complications, such as urinary tract infection, pneumonia, opportunistic pneumonia, and sepsis, were significantly more frequent in patients receiving higher doses of glucocorticoids — specifically, 76% vs. 41%. The frequency of herpes virus infections was not significantly different between groups.

After controlling for confounding factors, the team found that the glucocorticoid dose after six months was the only factor with a significant effect on pneumonia rates.

Irreversible physical damage, estimated by the Vasculitis Damage Index (VDI), after one year also was significantly higher in patients receiving doses of 7.5 mg or higher after six months

The researchers recognized the limitations to their study, specifically that it was designed retrospectively and had a small patient number. In addition, less common side effects associated with glucocorticoids therapy could not be assessed.

But overall, “this study shows that an extended glucocorticoid maintenance therapy in AAV patients induces severe infectious complications such as sepsis and pneumonia, leading to an increased frequency of death by infection,” the researchers wrote.

“Our data conclusively indicate that GC [glucocorticoids] tapering and discontinuation should be critically revised on a regular basis during the aftercare of AAV patients,” they concluded.