Early Disease Status Predicts Long-term Outcomes in AAV Patients, Study Suggests

Disease status at three and six months seems to predict long-term survival and kidney failure in patients with ANCA-associated vasculitis (AAV), a study shows.

These findings suggest that early disease control could be used as a surrogate endpoint, or objective, for AAV clinical trials, potentially shortening their duration.

The study, “Effect of disease activity at three and six months on long-term outcomes in ANCA associated vasculitis,” was published in the journal Arthritis and Rheumatology.

AAV is an autoimmune condition characterized by the destruction and inflammation of small blood vessels. The disease may affect several organs — including the skin, kidneys, stomach, intestine, and lungs — and clinical signs vary widely among patients.

Mortality rates of AAV patients have decreased dramatically in the past 20 years, but patients still face a higher risk of death than healthy individuals of the same age and sex.

Nonetheless, clinical trials for the condition usually use disease remission or relapse as primary endpoints, causing them to last several months or years. In addition, most trials don’t take into account the time it takes for a patient to achieve disease remission, or the impact of early relapse on these patients.

In an attempt to improve the quality of AAV clinical trials and shorten their duration, researchers at the University of Cambridge in the U.K. examined if early disease control — at three and six months — could be used to predict the risk of death and end-stage renal disease (ESRD) in these patients.

ESRD occurs when the kidneys no longer work as they should, and patients need dialysis or a kidney transplant to remain alive.

Researchers used data from four clinical trials — CYCAZAREM, NORAM, MEPEX, and CYCLOPS — conducted between 1995 and 2002 by the European Vasculitis Society, and their long-term registry data.

They examined a total of 354 patients, at a median age of 61 years, who had entered the trials with a new diagnosis of AAV. Most patients (55.9%) had granulomatosis with polyangiitis, followed by 40.7% with microscopic polyangiitis.

Depending on their disease activity at three and six months, patients in the study were divided into four groups: those with sustained remission, defined as remission by three months that was sustained until six months without relapse; those with late remission, defined as remission between three and six months; patients with relapsing disease, defined as remission by three months, but relapse by six months; and those with refractory disease, defined as no remission by six months.

Overall, 79.9% of patients achieved sustained remission, 10% had late remission, 5.2% experienced relapsing disease, and 5.2% had refractory disease.

After a median follow up of 5.7 years, 13% of patients developed ESRD, 18.6% died, and 25.1% either died or developed ESRD.

Disease status at six months was a significant predictor of both death and ESRD. Compared with patients with sustained remission, those with late remission were 3.3 times more likely to die during the study period. The chances of dying among patients with relapsing and refractory disease were also six times higher.

No patients in the remission group developed ESRD. But patients with relapsing disease were 34 times more likely to experience this disease symptom than those on sustained remission, and patients with refractory disease had a nearly 10 times higher chance of ESRD.

The risk of death was also influenced by age and kidney function at six months, while sex, year of enrollment, and kidney function at six months affected the risk for ESRD.

Researchers also examined a composite measure of death and ESRD. Consistent with the findings for death and ESRD alone, this measure was significantly associated with age, kidney function, and disease status at six months.

Patients who achieved remission and then relapsed had the worst outcomes, being 8.2 times more likely to die or develop ESRD than those with sustained remission.

“Objective parameters obtained early in the course of the disease course may predict long-term outcomes and early sustained remission may be an important goal of therapy,” the researchers concluded. “This study establishes early surrogate markers for long-term outcomes of value to future clinical trials shorter follow-up durations.”

Researchers, however, caution that increasing treatment doses to achieve early remission should be considered carefully, as the risk of treatment toxicity may also increase.