Tailored treatment tied to favorable outcomes in older AAV adults: Study
They may partially mitigate higher risk of infection, mortality with advancing age
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Older adults with ANCA-associated vasculitis (AAV) may achieve more favorable outcomes when induction therapy — an often intensive treatment approach aimed at quickly bringing active disease under control — is tailored to frailty and disease severity, a study suggests.
Among adults ages 75 and older with severe active AAV receiving tailored treatment, 20% died within the first year, which the researchers noted is comparable to the rate reported in younger patients or those with less severe disease. While serious infections remained common, increasing age was not associated with a higher risk of infections.
Because induction therapy can raise the risk of complications in frail older adults, these results suggest that “tailoring remission induction strategy according to a holistic assessment of frailty and disease activity may partially mitigate the higher risk of infection and mortality with advancing age,” researchers wrote.
The study, “Incorporating frailty and disease severity into treatment decisions for older patients with ANCA-associated vasculitis,” was published in Rheumatology.
Treating older adults can be particularly challenging
AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels. While the disease can affect any organ, it most commonly involves the kidneys and lungs.
Induction therapy, the initial treatment used to achieve remission and prevent organ damage, often includes a course of corticosteroids that rapidly suppress inflammation alongside immunosuppressive therapies such as rituximab (sold as Rituxan and others, with biosimilars available) or cyclophosphamide.
Treating older adults, however, can be particularly challenging. While these therapies may be needed to control severe disease, they can also raise the risk of serious infections and other complications in frail patients.
Yet, older adults, especially those aged 75 and older, have often been underrepresented or excluded from clinical trials evaluating induction therapy regimens.
“Excluding older patients diminishes the real-world applicability of trial findings and restricts the evidence base needed to guide treatment decisions for older people living with AAV,” the researchers wrote.
Kidney involvement common in participants
To better understand outcomes in this population, a team of researchers retrospectively analyzed data from 84 hospitalized adults ages 75 and older who started induction treatment for severe active AAV at Addenbrooke’s Hospital in the U.K. between 2014 and 2021.
At that hospital, treatment decisions for older patients “are tailored according to a combined assessment of frailty (functional status, age, [co-existing conditions]) and disease severity,” the researchers wrote.
Participants (47.6% men had a median age of 79 (range, 75 to 93). The majority (79.8%) had newly diagnosed disease, and most commonly had a diagnosis of microscopic polyangiitis (66.6%), the AAV type that is more common in China and Japan.
Kidney involvement was common, affecting 76.2% of participants. When first admitted, one in five (20.2%) required dialysis, a therapeutic procedure that essentially takes over the kidneys’ job when they fail.
Participants received one of four treatment approaches according to frailty and disease severity: standard-dose rituximab (40%), cyclophosphamide alone (26.2%), low-dose rituximab (22.3%), or a combination of rituximab and cyclophosphamide (10.7%). Corticosteroids, given as short into-the-vein courses of methylprednisolone, were used in half of the patients.
Combination therapy with rituximab and cyclophosphamide was more often reserved for relatively younger patients within the group, ages 75-80, and for those with more active disease. Cyclophosphamide, either alone or combined with rituximab, was also used more often in people with severe kidney involvement or those requiring dialysis.
By contrast, low-dose rituximab was more commonly prescribed to the oldest and frailest patients, including those older than 85 and those requiring residential or nursing home care.
Meanwhile, methylprednisolone was more commonly used alongside cyclophosphamide-based regimens in patients with greater disease activity and those with more severe kidney disease.
Increasing age was not associated with a greater risk of infection
Participants were followed for a median of 21 months, or slightly less than two years. Within six months of treatment, 71 participants (84.5%) achieved complete remission, while the remaining 13 (15.5%) had died.
Among the 17 people who required dialysis when first admitted, eight (47.1%) recovered sufficient kidney function to discontinue the treatment, six (35.3%) remained dialysis-dependent, and three (17.6%) died.
Among the 80 patients discharged from the hospital, 40% experienced at least one serious infection during follow-up, and 27% were readmitted with a serious infection within one year.
Increasing age was not associated with a greater risk of infection, suggesting that “selection of induction regimen based on age and frailty may have mitigated the higher risk of infection” associated with advanced age, the researchers wrote.
Overall, 28 patients (33.3%) died during follow-up, including 20% within the first year, with mortality being lowest in the combination therapy group (10%) and highest in the low-dose rituximab group (26%). Older age was significantly associated with increased mortality.
The researchers emphasized that a 20% mortality rate is comparable to that previously reported in younger or less severely ill AAV patients and lower than the roughly 47% previously reported in an elderly AAV patient group.
It is “crucial” that studies evaluating induction regimens “avoid arbitrary upper age limits” so that clinical trial findings better reflect real-world practice and “inform care for everyone affected by AAV,” the team concluded.
