Tavneos found just as safe, effective in older AAV patients as younger
Trial analysis examined use of approved therapy in patients 65 and older
Adding Tavneos (avacopan) to standard treatment is as safe and effective in older people with ANCA-associated vasculitis (AAV) as it is among younger patients, according to the findings of a post-hoc analysis of clinical trial data.
The approved oral therapy “showed similar efficacy and safety results in patients aged … 65 years [and older] compared with those aged [younger than] 65 years,” the researchers wrote.
The international team of scientists were evaluating the results of a Phase 3 clinical trial, dubbed ADVOCATE (NCT02994927), that had supported Tavneos’ approval in the U.S., the European Union, and other regions. The therapy is indicated for people with granulomatosis with polyangiitis, called GPA, and microscopic polyangiitis, or MPA, the two most common types of AAV.
Here, the team conducted a post hoc analysis, meaning one that’s planned and conducted after a trial has been completed, to assess Tavneos use in older patients, whom, the researchers noted, have a high risk of adverse effects and complications with other treatments.
Their study, “Efficacy and safety of avacopan in patients aged 65 years and older with ANCA-associated vasculitis: a post hoc analysis of data from the ADVOCATE trial,” was published in the journal Rheumatology.
Researchers assessed data from Phase 3 ADVOCATE trial
AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels, which leads to problems in the kidneys and other organs.
The development of GPA and MPA peaks in individuals ages 65 and older, and these patients often experience more kidney involvement and worsening kidney function than younger people with the condition. Older AAV patients, especially those 75 years and older, also have a higher risk of other health conditions, and of death within the first six months of diagnosis, often due to infections, research has shown.
Traditionally, AAV treatment has relied on glucocorticoids, which are anti-inflammatory drugs. However, their long-term use can lead to serious side effects.
An oral therapy, Tavneos works by blocking the alternative complement pathway, an immune pathway involved in several mechanisms that drive AAV. It is approved in several countries, including the U.S., as an add-on to standard medications like glucocorticoids for adults with severe and active GPA or MPA.
The yearlong ADVOCATE trial tested Tavneos against a high dose of the glucocorticoid prednisone in 330 GPA and MPA patients given also standard immunosuppressive treatment.
The data showed that Tavneos was better than prednisone at promoting long-term remission and improving kidney function and health-related quality of life. Importantly, it also helped reduce glucocorticoid use.
While older patients are often underrepresented in clinical trials, ADVOCATE had enrolled patients of all ages, including those older than 65.
In this study, the researchers now focused on the subgroup of 160 patients who were ages 65 and older at the study’s start, or baseline. A total of 109 patients were ages 65 to 74, while 51 were 75 or older.
Tavneos reduced glucocorticoid dosage for both older, younger patients
The researchers found that sustained remission rates were similar to those previously reported in the total study population. After 52 weeks, or one year, 54.4% to 66.3% of patients across all age groups were in remission, with higher proportions seen among those given Tavneos than among those on prednisone.
Percentage differences between the Tavneos and placebo groups were 11.8% for patients younger than 65, 9.9% among those ages 65-74, and 9.4% for those older than 75.
Relapse rates also were lower in the Tavneos versus prednisone groups: 10.7% versus 22.4% in the younger group, 12.3% versus 18.8% in the 65-74 age group, and 3.8% versus 20.8% in the oldest group.
Both groups of older patients had poorer kidney function at baseline, as evidenced by a lower eGFR, or estimated glomerular filtration rate, a validated measure of kidney function.
Kidney function improved in all age groups over one year, regardless of whether patients received Tavneos or prednisone. However, the greatest mean eGFR improvement was seen among patients ages 75 and older treated with Tavneos (by 10.7 vs. 7.8 mL/min/1.73 m2). These improvements were greater than those seen with prednisone (by 7.8 mL/min/1.73 m2).
For those ages 65-74, the difference between Tavneos and placebo groups in terms of eGFR change was minimal.
The addition of [Tavneos] to the standard of care in the treatment of older adults … with GPA or MPA is associated with efficacy and safety similar to that observed in younger adults and should be considered in this older population, who remain at higher risk of poor outcomes.
The therapy also reduced glucocorticoid dosage after one year: by 55% in the younger group, 61% in the 65-74 age group, and 49% in the oldest group. Participants treated with Tavneos also had lower glucocorticoid toxicity index scores across all age groups.
Patients’ health-related quality of life improved with Tavneos treatment across all age groups, as shown by higher scores after one year in the physical and mental components of the 36-Item Short Form Health Survey (SF-36), the EuroQoL Group 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) visual analogue scale, and the EQ-5D index score.
The only exception was SF-36’s mental component in patients 75 and older, which showed slightly higher scores in the prednisone group.
The rates of adverse events and serious adverse events were similar between the Tavneos and prednisone groups among patients ages 65-74 and those 75 and older — and among those seen for the younger group.
“The addition of [Tavneos] to the standard of care in the treatment of older adults … with GPA or MPA is associated with efficacy and safety similar to that observed in younger adults and should be considered in this older population, who remain at higher risk of poor outcomes,” the researchers wrote.
Overall, “this analysis supports the use of [a Tavneos-based] regimen in older patients with GPA or MPA to minimize glucocorticoid-related risks,” they concluded.
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