Glucocorticoid Maintenance Therapy Linked to Severe Infectious Complications in ANCA-Associated Vasculitis

In patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), extended glucocorticoid maintenance therapy increases the risk for severe infectious complications and mortality and has no effect on time to relapse or survival, according to study results published in Rheumatology International.

The objective of the current study was to determine the effect of glucocorticoid maintenance therapy and treatment duration on outcomes, including survival, time to relapse, kidney function, infectious complications, and irreversible physical damage, in patients with AAV.

The study included 130 patients with newly diagnosed granulomatosis with polyangiitis or microscopic polyangiitis who received treatment at 2 different German vasculitis centers between August 2004 and January 2019. Participants received induction therapy with cyclophosphamide and glucocorticoids, followed by maintenance therapy with glucocorticoids.

Researchers compared the outcomes between 76 patients who received treatment according to a predefined glucocorticoid reduction scheme (<7.5 mg) and 54 patients who received 7.5 mg or more of glucocorticoids, 6 months after the first start of induction therapy.

Compared with patients receiving less than 7.5 mg of glucocorticoids after 6 months, patients on extended glucocorticoid maintenance therapy receiving 7.5 mg or greater had an increased risk for infections (0.6 vs 1.7 infectious episodes per patient; P <.001), including urinary tract infections (P =.007), pneumonia (P =.003), opportunistic pneumonia (P =.022), and sepsis (P =.008).

Incidence of pneumonia during the first 2 years after disease onset was 3-fold greater among patients receiving a high glucocorticoid maintenance dose (hazard ratio, 3.0; 95% CI, 1.5-6.1). Statistical analysis indicated that glucocorticoid dose after 6 months was the only identified factor with a significant impact on the incidence of pneumonia.

There was no difference between the groups with regard to risk for relapse (P =.93), time to relapse (P =.80), refractory disease (P =.67), or patient survival (P =.31). In addition, after a 4-year follow-up, no difference was reported between the groups in kidney function or incidence of end-stage kidney disease.

These findings indicated that glucocorticoid maintenance therapy of 7.5 mg or greater after 6 months was associated with more severe infectious complications, with an increased frequency of deaths from infection. However, glucocorticoid maintenance therapy was not observed to have an effect on time to relapse or patient survival.

The study had several limitations, including the relatively small sample size and different patient numbers in the groups, with fewer patients in the group receiving 7.5 mg or more of glucocorticoid treatment.

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

Reference

Speer C, Altenmüller-Walther C, Splitthoff J, et al. Glucocorticoid maintenance therapy and severe infectious complications in ANCA‑associated vasculitis: a retrospective analysis. Rheumatol Int. Published online 22 November, 2020. doi:10.1007/s00296-020-04752-9