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MANCHESTER, England — In real-world practice, the use of avacopan (Tavneos) is much broader than it was in the phase 3 clinical trial that led to its approval for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV), according to a retrospective, multicenter cohort study presented at the British Society for Rheumatology (BSR) 2025 Annual Meeting.

Compared with individuals who were treated with the C5a receptor inhibitor avacopan as part of the phase 3 ADVOCATE trial, patients treated in the real-world setting had more severe renal disease, were generally treated later, and received concomitant immunosuppressants. They also underwent a variety of glucocorticoid-tapering protocols, unlike the set tapering protocol that was used in the clinical trial.

Study presenter Samuel Wood, a rheumatology trainee and clinical research fellow at Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, England, said that real-world data were lacking so far for avacopan, particularly in people with severe end-organ manifestations such as reduced renal function, after the drug was first licensed for use in England and in the European Union in 2022 and after initial approval in the United States in 2021. Avacopan is licensed for use in combination with standard therapy (rituximab or cyclophosphamide), including glucocorticoids.

To look at how the drug had been used since its approval, Wood and associates created a cohort of 123 patients with AAV, 61 of whom has been treated with avacopan at seven centers in England. The remaining 62 patients were taken from a historical cohort treated with rituximab or cyclophosphamide between 2017 and 2019. The researchers employed a statistical method used to adjust for confounding bias in observational studies, inverse probability weighting, to compare the groups in terms of rates of clinical response (Birmingham Vasculitis Activity Score [BVAS] v3.0 ≤ 3 and a prednisolone dose ≤ 5 mg/d or equivalent) and complete remission (BVAS of 0 and not on oral prednisolone).

Comparison With ADVOCATE

Looking first at how the 61 avacopan-treated patients in the real-world cohort compared with people who had been treated in the clinical trial (n = 166), Wood reported that avacopan had been started a mean of 2.9 weeks from the initial induction therapy with rituximab or cyclophosphamide.

“Admittedly, this study was performed in the very early phases of using avacopan. So, these delays are likely to be related to both clinician awareness of treatment and also the pharmacy getting hold of the actual treatment itself,” Wood said.

Notably, the real-world avacopan cohort differed from the ADVOCATE trial population at baseline in that 12 (19.7%) patients had an estimated glomerular filtration rate (eGFR) ≤ 15 mL/min/1.73 m², and concomitant immunosuppression was used in 17 (27.9%), vs none of the trial participants. Moreover, 14 (22.9%) of the real-world patients had received a combination of cyclophosphamide and rituximab, compared with none in ADVOCATE. 

Wood reported that clinical response criteria were met in 32 (64%) of the patients treated with avacopan in the real-life setting who had 6 months of follow-up data available, and in 14 (78%) of 18 patients who had follow-up data available at 12 months.

Just over one third (36%) of patients had stopped glucocorticoid therapy, and only two of these had experienced a flare of their symptoms by 12 months. 

However, only seven (14%) patients would have met the ADVOCATE primary endpoint of clinical remission at 6 months, Wood pointed out. 

Avacopan’s Effects in Severe Renal Impairment

Looking more closely at how avacopan fared in people with severe renal impairment, Wood noted that 10 of the 12 patients with a baseline eGFR ≤ 15 mL/min/1.73 m² had follow-up data available at 6 months. Eight of those 10 exhibited an increase in eGFR ≥ 15 mL/min/1.73 m². The mean increase in eGFR at 6 months was 13.3 mL/min/1.73 m².

Safety appeared comparable between the real-world and trial-treated patients. Out of 12 patients, just two stopped avacopan treatment because of side effects and three had a serious adverse event during follow-up, including one infection, one hospital admission with heart failure, and one hospital admission with epistaxis.

 Wood pointed out that even in patients with any renal involvement, there were significant improvements between baseline and 6 months in eGFR, serum creatinine level, and urine protein-to-creatinine ratio.

Comparison With Historical Cohort

Comparing the real-world avacopan-treated patients vs the historical cohort of patients who only had a glucocorticoid taper following induction therapy with rituximab or cyclophosphamide, avacopan-treated patients were found to be significantly older (mean age, 60 vs 53 years), have a significantly shorter disease duration (median, 6.14 vs 41.9 weeks), have a significantly higher baseline BVAS v3.0 score (16.2 vs 12.3), and use a significantly higher mean dose of prednisolone (41.6 vs 20.8 mg).

After inverse probability weighting, however, avacopan-treated patients were 4.6 times more likely to have a clinical response at 6 months than the steroid taper group (P = .015). Despite looking at multiple variables, no predictors of clinical response to avacopan at 6 months were found.

In terms of safety, avacopan was discontinued in 29 patients, but this was due to completion of a 12-month course of treatment in approximately half of cases (n = 15; 51.7%). Other reasons for discontinuation were raised aminotransferase levels in three patients; gastrointestinal intolerance in two patients; and one case each of leg swelling, breathlessness, anemia, and infection. Two deaths occurred: one due to chest infection and one due to myocardial infarction. There was one case of drug intolerance, and two cases in which the clinician considered the drug to be ineffective and so stopped the treatment. 

Twenty-five serious adverse events were reported, but the severe infection rate in the avacopan-treated and non–avacopan-treated groups were similar, with 11 infections in nine patients and 14 infections in 12 patients, respectively. This yielded rates of serious infections per 100 patient-years of 19.2 and 20.8. 

In commenting about the study for Medscape Medical News, session chair Christopher Denton, MD, PhD, professor of experimental rheumatology at UCL Medical School and head of the Centre for Rheumatology at the Royal Free Hospital, London, England, spoke of the importance of gathering real-world data.

“One of the challenges, of course, when you do clinical trials is that they are necessarily restrictive and there is use of a drug over relatively short time,” he said. “In the real world, you've got the opportunity to see how a drug fits in with background treatment over a much longer period of time.”

Denton added, “The two approaches are really complementary, and postmarketing surveillance and observational studies in the real world are really, really important, because often they show that drugs work outside the population or context that they were tested in the trial.”

The study was independently supported. Wood reported having no conflicts of interest. Denton had no relevant financial relationships to report. 

Sara Freeman is a medical journalist based in London, England.