Tavneos similar to glucocorticoids in treating AAV-related kidney disease
Study: Both groups experienced improved function after 6 months
Tavneos (avacopan) plus a short course of glucocorticoids is as effective as glucocorticoids alone for treating rapidly progressive glomerulonephritis (RPGN), a severe kidney disease, in adults with ANCA-associated vasculitis (AAV), a study reports.
“At month 6, patients receiving [Tavneos] and transient or low doses of GCs [glucocorticoids] have similar kidney outcomes to patients who received an induction regimen with conventional doses of GCs,” researchers wrote.
In addition, certain features on kidney biopsy at the time of RPGN diagnosis were significantly associated with maximal kidney improvement after six months of treatment.
Together, these results highlight “how underlying kidney [structural abnormalities] can influence the best possible kidney response in severe [AAV-RPGN],” researchers wrote.
The study, “Avacopan or Glucocorticoids for Severe Antineutrophil Cytoplasmic Autoantibody–Associated Rapidly Progressive Glomerulonephritis,” was published in the journal Kidney International Reports.
Tavneos targets part of the immune system that goes awry in AAV
AAV is a group of autoimmune diseases where small blood vessels become inflamed and sustain damage. The kidneys are commonly affected and may show RPGN, a rapid decline in kidney function related to injury in the glomeruli, the kidney’s filtering units.
Kidney biopsies from people with AAV-related RPGN show characteristic disease signs, including glomeruli scarring, or glomerulosclerosis, and crescent-shaped areas of rapidly growing cells.
Medication to suppress the immune system is typically part of AAV-related RPGN treatment. Glucocorticoids, a group of anti-inflammatory medications, are commonly used off-label, but their long-term use is linked to serious side effects.
In the past four years, Tavneos, which targets a part of the immune system that goes awry in AAV, was approved in most regions as an add-on to AAV standard treatment and has shown potential to decrease glucocorticoid dependence.
Either treatment may be combined with the immune cell-killing therapies cyclophosphamide (sold as Cytoxan and others), rituximab (marketed as Rituxan and others), or both.
However, “there are still uncertainties regarding the best immunosuppressive regimen in severe forms of RPGN” because patients with the poorest kidney function “have been excluded from most studies, and kidney biopsy has not been a prerequisite for inclusion,” the researchers wrote.
Limited patient data at 1 year suggests benefits persisted over long term
With this in mind, a team of researchers in France retrospectively examined records from 50 adults with severe AAV-related RPGN who received glucocorticoid-based therapies and 20 who received Tavneos-based therapies at a French hospital. The latter participants were part of a larger observational clinical study (NCT05318196).
All had undergone a kidney biopsy to confirm RPGN and had been followed for at least six months after treatment.
In the glucocorticoid group, 30% of participants were also on cyclophosphamide, 54% were also on rituximab, and 16% were on both. In the Tavneos group, all received rituximab, with 10% taking cyclophosphamide as well. Many in the latter group also received glucocorticoids, but for a significantly shorter period than in the other group (a mean of 1.9 months vs. 15 months).
Half of the participants in each group also underwent plasma exchange, a blood-cleaning procedure meant to help remove the self-reactive antibodies that drive AAV.
Kidney biopsy samples with greater areas of characteristic glomerular crescents correlated significantly with poorer kidney function, as reflected by a lower estimated glomerular filtration rate (eGFR). However, there was no similar association between the extent of glomerulosclerosis and kidney function.
When the team evaluated the treatments’ effect on kidney function, they found that both treatment groups experienced similar eGFR increases after six months, indicating improved kidney function.
The development of new drugs to control [body-wide] AAV … or the RPGN itself …. acts as a prompt to better categorize patients into clusters according to their underlying [tissue] or molecular kidney patterns, and their potential for kidney recovery.
Limited patient data at one year suggested these benefits persisted over the long term, highlighting “that an early … and intensive regimen … is required to optimize short- and long-term kidney outcomes,” the researchers wrote.
Further statistical analyses showed that none of the treatments were significant predictors of kidney outcomes after six months. However, a lower percentage of glomerulosclerosis was significantly associated with a higher chance of kidney function improvements.
This “highlights how an accurate comparison of kidney responses to therapies requires adjustment for kidney biopsies in patients with [AAV-RPGN],” the researchers wrote.
Patients in either group showed comparable overall survival. Three Tavneos-treated patients discontinued the therapy after two to three months due to reversible hepatitis, or liver inflammation.
These results could have implications for clinical trials, in which investigators may need to consider glomerulosclerosis and other factors when assessing the strength of participant responses to therapies.
“The development of new drugs to control [body-wide] AAV … or the RPGN itself …. acts as a prompt to better categorize patients into clusters according to their underlying [tissue] or molecular kidney patterns, and their potential for kidney recovery,” the team wrote.
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