Serious Infections Found to Mostly Occur in 1st Year After Diagnosis

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Serious infections occur more frequently in people with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis who have higher disease activity at diagnosis, a real-world, long-term study showed.

Moreover, most serious infections occur during the first year after the ANCA vasculitis diagnosis, the study found.

The findings also showed that those treated initially with cyclophosphamide have a higher incidence of serious infections than patients who received the biologic therapy rituximab.

The study, “Serious infections in ANCA-associated vasculitides in the biologic era: real-life data from a multicenter cohort of 162 patients,” was published in the journal Arthritis Research & Therapy

ANCA vasculitis is a group of autoimmune disorders characterized by the inflammation of and damage to the blood vessels. Most standard treatments for ANCA vasculitis suppress the immune system to limit the damage. 

Studies have suggested that serious infections are more frequent in ANCA vasculitis patients compared with the general population of the same age, and that such infections increase the risk of mortality. This is especially a concern in the early stages of the disease — namely in the first year after diagnosis. 

Although long-term extension studies from clinical trials have provided useful data regarding the incidence and risk factors for serious infections in this patient population, real-world data are limited.

To address this question, a team led by investigators based at the National and Kapodistrian University of Athens School of Medicine, in Greece, examined the medical records of 162 adults with ANCA-associated vasculitis. These patients were treated at three local centers over a 30-year period from 1990 to 2020.

The participants’ mean age was 60.9 years, 51.9% were men, and the mean follow-up was of 5.4 years. Of the ANCA vasculitis types, 102 patients had granulomatosis with polyangiitis, known as GPA, and 60 had microscopic polyangiitis or MPA. 

Serious infections included those needing hospitalization or intravenous (into-the-vein) antibiotics, all cases of herpes zoster — the shingles virus — and any other opportunistic infections. 

A total of 61% of patients initially received treatment with the immunosuppressant cyclophosphamide, sold under the brand name Cytoxan, among others. Another 18% were given rituximab, sold under the brand name Rituxan, among others, while 9% were treated with both therapies in addition to glucocorticoids such as prednisolone. The remainder were given other agents such as methotrexate.

During the follow-up period, 50 patients (32%) developed 67 serious infections with an overall incidence rate of 7.5 per 100 patient-years. The mortality rate during this time was 9.2% (15 patients died).  

Almost half of the infections were found in the respiratory tract (45%), followed by herpes zoster (24%), digestive tract (9%), bacteria in the bloodstream (9%), and urinary tract infections (9%). 

Most infections (42%) occurred during the first year after diagnosis. Specifically, the first year’s incidence rate was 18.6 per 100 patient-years. That compared with incidence rates, per 100 patient-years, of 6.2 in the second year and 5.7 in the third year. Beyond the fourth year, the rate was 4.7 per 100 patient-years.

Compared with patients without serious infections, those diagnosed with them were more likely to have received dialysis or plasma exchange (PLEX) — 8.9% vs. 29% in the group with serious infections. Of note, PLEX is a treatment that removes and replaces a patient’s blood plasma.

More infections also occurred in patients with a higher initial prednisolone dose and a lower eGFR, which is a measure of kidney function. Patients with more co-existing medical conditions (comorbidities), and a higher degree of disease activity based on the Birmingham Vasculitis Activity Score (BVAS) also experienced more infections. 

Statistical analysis showed that patients who received PLEX or dialysis had about a five times higher risk of developing a serious infection than those who did not. Specific risk factors for infection included impaired kidney function at diagnosis (eGFR lower than 30 mL/min), older age, and the need for PLEX or dialysis. 

When looking only at the first year after disease diagnosis, the researchers found that 23 participants (14%) experienced serious infections. Compared with patients without an infection, they were older (68.2 vs. 59.7 years), were more likely to need PLEX or dialysis (39% vs. 11%), had a history of diabetes (43.5% vs. 14.5%), and received cyclophosphamide combined with rituximab (19% vs. 3.7%). Such infections also were found among those with worse kidney function and more disease activity, and patients given a higher dose of prednisolone at diagnosis.

According to a statistical analysis, the need for PLEX and/or dialysis, as well as higher disease activity at diagnosis, were independent predictors of a serious infection during the first year after diagnosis. 

The incidence of serious infections was higher during the initial treatment phase than in the maintenance or off therapy phases. Individuals given cyclophosphamide at diagnosis or relapse had a higher incidence of infections compared with those treated with rituximab — 19.34 vs. 11.34 per 100 patient-years. 

Regarding the maintenance phase, there was no difference in the incidence of infections between those treated with various immunosuppressives or being off-therapy and participants treated with rituximab. 

Finally, in comparison with those who started treatment with cyclophosphamide or rituximab, patients initially given a combination of both therapies had a higher incidence of infection during the first year after diagnosis.

In conclusion, “during the 5-year follow-up period, the overall incidence of [serious infections] in our [ANCA vasculitis] patients was 7.5 per 100 patient years which is much lower to the incidence reported in older studies,” the researchers wrote. “This decreasing incidence could be attributed to the better overall care of these patients and the limited use of [cyclophosphamide] … for extended periods of time.”

The incidence of serious infections was “predominantly determined by the baseline disease activity, time after diagnosis, and the treatment regimens used,” the researchers wrote, being highest during the first year after diagnosis with a decreasing trend over time, and with cyclophosphamide treatment in the initial phase.

“Our results emphasize the challenges that caring physicians are facing for the treatment of [ANCA vasculitis] and highlight the unmet needs for safer treatment regimens, especially during the early phases of the disease,” the team concluded.