Main Research Findings

Avacopan, a selective C5a receptor (C5aR) antagonist, has shown promising results in treating anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). 2 Avacopan's mechanism involves inhibiting neutrophil priming induced by the complement component C5a, a crucial process in AAV pathogenesis. 2 Preclinical studies have demonstrated that avacopan effectively suppresses neutrophil chemotaxis and priming induced by C5a-C5aR signaling, leading to significant reduction in nephritis and renal damage in an ANCA-induced glomerulonephritis mouse model. 2 In the global Phase 3 trial, ADVOCATE, avacopan achieved non-inferiority to prednisone in inducing remission at week 26 and superiority in sustained remission at week 52 for MPA and GPA patients. 2 Additionally, avacopan demonstrated a significantly lower GC toxicity score, fewer GC-related adverse events, and improved renal function, as evidenced by an increase in estimated glomerular filtration rate (eGFR) compared to prednisone. 2

While avacopan holds great promise as a potential treatment for AAV, early switching from glucocorticoids to avacopan during induction therapy has been explored in some cases. 1 This approach could potentially mitigate glucocorticoid toxicity and improve treatment outcomes. However, more case reports and research are needed to clarify the role of avacopan in AAV induction and maintenance therapy. 1

Reason for Side Effects

Avacopan's mechanism of action involves inhibiting the C5a receptor of the complement system. This system plays a crucial role in immune defense, particularly against infections. Therefore, inhibiting the complement system with avacopan can potentially increase the risk of infections.

Common Side Effects

Infections

The use of complement modulators, including avacopan, can increase the risk of infections. 6

Liver Function Abnormalities

Avacopan may cause liver function abnormalities. 1

Countermeasures for Side Effects

Infection Prevention

Due to the heightened risk of infections during avacopan treatment, taking preventive measures is essential. These include practicing good hygiene habits such as hand washing and gargling, as well as receiving necessary vaccinations.

Liver Function Monitoring

Regular monitoring of liver function is crucial during avacopan treatment. If liver function abnormalities are detected, appropriate interventions such as discontinuing avacopan may be necessary.

Comparison Between Studies

Commonalities Among Studies

Multiple studies consistently highlight the effectiveness of avacopan in treating AAV. Compared to conventional steroid therapies, avacopan appears to exhibit fewer side effects and may potentially improve renal function.

Differences Among Studies

Current research on the safety and efficacy of avacopan is still ongoing and needs further expansion. Long-term safety data, particularly regarding long-term avacopan administration, require further investigation. Additionally, determining the optimal dosage and administration methods for avacopan warrants further research.

Cautions Regarding Application in Daily Life

While avacopan holds promise for AAV treatment, the potential for side effects, such as the risk of infections, needs to be considered. Therefore, consulting a physician and carefully tailoring treatment plans to individual circumstances are essential when considering avacopan therapy.

Limitations of Current Research

Research on the safety and efficacy of avacopan is still limited. More extensive research, particularly on long-term safety following prolonged avacopan administration, is crucial. Furthermore, identifying the optimal dosage and administration methods for avacopan necessitates further research.

Future Research Directions

To further validate the safety and efficacy of avacopan, long-term follow-up studies are essential. Additionally, conducting more clinical trials to elucidate the optimal dosage and administration methods for avacopan is a priority.

Conclusion

Avacopan presents a promising new treatment option for ANCA-associated vasculitis, with the potential to reduce steroid use and improve renal function. However, it is essential to be aware of potential side effects, such as the risk of infections. Consulting a physician and carefully tailoring treatment plans to individual circumstances are essential when considering avacopan therapy.