Avacopan linked to fewer severe infections in ANCA-associated vasculitis

Design

Multicentre retrospective cohort with time-varying exposure and weighting

Population

387 patients with ANCA-associated vasculitis (52 on avacopan)

Primary outcome

Severe infection requiring hospitalisation and recurrent relapse

Effect

Severe infection adjusted HR 0.22 (0.07 to 0.68); relapse not significantly different

This multicentre retrospective cohort (REVEAL) included 387 patients with ANCA-associated vasculitis, 52 of whom received avacopan, a C5a receptor antagonist used to reduce glucocorticoid exposure. Avacopan use was modelled as a time-varying exposure with inverse probability weighting.

Avacopan exposure was associated with a lower risk of severe infection requiring hospitalisation (adjusted HR 0.22, 95% CI 0.07 to 0.68). Patients on avacopan also had lower prednisolone exposure over time. No significant difference in recurrent relapse was seen. The infection association held in direction when models accounted for glucocorticoid dose, though its size varied.

Infection is a leading cause of early death in ANCA vasculitis, and much of it is driven by glucocorticoids. This real-world signal supports the steroid-sparing rationale for avacopan seen in trials. With only 52 treated patients and observational allocation, the size of the benefit is uncertain, and cost will limit access in many settings.

• Consider avacopan as part of a glucocorticoid-sparing induction strategy in ANCA-associated vasculitis where available.
• Taper prednisolone actively; lower glucocorticoid exposure travelled with fewer infections.
• Maintain infection prophylaxis, including against Pneumocystis, during induction.
• Do not expect avacopan to reduce relapse on the basis of this cohort; no difference was seen.

Why it matters

It adds real-world support to the idea that cutting steroids cuts infections in vasculitis.

Don't overread it

Observational with 52 treated patients; the effect size varied between models and cannot be taken as causal.

The statistics, in plain English

An adjusted hazard ratio of 0.22 means severe infections occurred at about a fifth of the rate during avacopan exposure. The wide interval (0.07 to 0.68) reflects few events; the true reduction could be much smaller.

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