Tavneos plus rituximab induction aids sustained remission with AAV

Higher 1-year remission rates seen with Tavneos in ADVOCATE trial

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In a Phase 3 trial of Tavneos (avacopan) in people with ANCA-associated vasculitis (AAV), the therapy’s effectiveness in the subgroup of patients on standard induction treatment with rituximab was similar to that of the overall study population.

Reasonable safety also was seen, and sustained one-year remission was higher in this rituximab subgroup compared with a similar patient subgroup given prednisone as a taper treatment.

That’s according to the study “Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomized trial,” published in the Annals of the Rheumatic Diseases. The work was funded by ChemoCentryx, Tavneos’ original developer that was later acquired by Amgen.

“These results indicate the benefit of [Tavneos] for the treatment of AAV among patients also receiving RTX [rituximab] induction,” the researchers wrote.

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Tavneos is an oral therapy that’s approved to treat microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common types of AAV. It works to reduce disease-driving inflammation by suppressing the activity of a protein called the C5a receptor.

Tavneos’ approvals were supported mainly by data from the Phase 3 ADVOCATE clinical trial (NCT02994927), in which more than 300 MPA and GPA patients were given either Tavneos or the glucocorticoid prednisone, plus the disease’s standard induction treatment, for a year.

These therapies, designed to induce remission, included either cyclophosphamide followed by azathioprine or rituximab.

ADVOCATE results showed both Tavneos and prednisone led to comparable rates of disease control after about six months, while rates of sustained disease remission at one year were significantly higher for patients given Tavneos.

In addition, the Amgen therapy was associated with better kidney function and health-related quality of life, as well as with reduced glucocorticoid use.

Researchers now conducted a subgroup analysis of ADVOCATE, focusing only on the 214 patients (64.8%) who were on rituximab, an antibody-based treatment that works by killing B-cells, a type of immune cell implicated in AAV. The treatment was given once a week for four weeks.

“Because RTX is currently standard of care for induction of remission and maintenance of remission in AAV, this subgroup analysis of the ADVOCATE trial was conducted to evaluate the efficacy and safety of [Tavneos] in patients with GPA or MPA receiving background induction therapy with RTX,” the scientists wrote.

This patient group had a mean age of 59.8, 52.8% were male, and 84.6% were white. Most had GPA (60.3%), kidney involvement (76.2%), and more than half (58.4%) were newly diagnosed with AAV.

Demographic and clinical features generally “were similar between the two treatment [sub]groups and did not differ appreciably from the full study population,” the researchers wrote.

Results also were generally similar to what was seen in the overall study population: After six months, disease remission was achieved by about three-quarters of patients in both the Tavneos (77.6%) and prednisone groups (75.7%). After one year of treatment, sustained remission rates were notably higher in the Tavneos group (71% vs. 56.1%).

“The results of this subgroup analysis suggest that [Tavneos] with background induction therapy with RTX showed comparable efficacy to a prednisone taper with background RTX in achieving remission at [six months] and a higher rate of sustained remission at [one year],” the researchers wrote.

Fewer patients in remission given Tavneos, versus prednisone, had a relapse

Among patients who achieved disease remission, less than 1 in 10 Tavneos-treated patients (8.7%) experienced a disease relapse during the study, compared with about 1 in 5 (20.2%) among those on prednisone. This represented a 58% lower risk of relapse for patients given Tavneos.

As expected, glucocorticoid use was lower in the Tavneos group, as was glucocorticoid-associated toxicity, measured using the Glucocorticoid Toxicity Index.

Measures of kidney function and health-related quality of life showed improvements with both treatments, but they were generally greater with Tavneos.

“Beyond the efficacy outcomes of remission and relapse rates, other outcomes reported in this study indicate benefits of [Tavneos] with background induction RTX therapy, including trends of [kidney] recovery and improvement in [health-related quality of life] outcomes,” the researchers wrote.

The proportion of patients experiencing serious adverse events and serious infections, as well as the number of such events, was higher in the prednisone group.

“This current subgroup analysis of the ADVOCATE trial demonstrates that among patients treated with RTX induction, use of [Tavneos], compared with a prednisone taper, can reduce [glucocorticoid] toxicity potentially ameliorating the burden of chronic, treatment-related harms for patients, without compromising efficacy,” the scientists concluded.