Antineutrophil Cytoplasm Antibody-Associated Vasculitis
Antineutrophil Cytoplasm Antibody-Associated Vasculitis
Mycophenolate mofetil, an oral immunosuppressant, has been used as an alternative agent for relapsing disease and in remission maintenance. As an induction agent mycophenolate mofetil has been studied in myeloperoxidase (MPO)-ANCA vasculitis in which it appears to compare well to cyclophosphamide in small studies. A larger induction study with mycophenolate mofetil in AAV, the MYCYC trial (ClinicalTrials.gov number; NCT00414128) has finished and is under analysis now. It will provide further information.
Gusperimus (15-deoxyspergualin) inhibits mainly T-cell maturation and cytotoxic T-cell proliferation but also B cells. Two open label studies reported high response rates in refractory GPA. Administered in 28-day cycles of daily subcutaneous injection with washout periods, it has required close monitoring to avoid cytopaenias. The SPARROW trial (ClinicalTrials.gov number; NCT01446211) is evaluating the efficacy of gusperimus in relapsing and refractory GPA.
Plasma exchange is a treatment option for severe AAV. Confirmation of the pathogenicity of ANCA has contributed to a therapeutic rationale for plasma exchange in AAV, although removal of other factors may also be important. Meta-analysis of plasma exchange trials suggests a beneficial effect on the risk of end-stage renal disease but no effect on mortality. Current practice recommends plasma exchange for those presenting with severe renal disease or alveolar haemorrhage with little evidence supporting the latter indication. The ongoing PEXIVAS trial (ClinicalTrials.gov number; NCT00987389) is examining the effect of plasma exchange on patient and renal survival in those with a GFR below 50 ml/min or severe alveolar haemorrhage.
Emerging Therapies With 'Conventional'-Type Drugs
Mycophenolate mofetil, an oral immunosuppressant, has been used as an alternative agent for relapsing disease and in remission maintenance. As an induction agent mycophenolate mofetil has been studied in myeloperoxidase (MPO)-ANCA vasculitis in which it appears to compare well to cyclophosphamide in small studies. A larger induction study with mycophenolate mofetil in AAV, the MYCYC trial (ClinicalTrials.gov number; NCT00414128) has finished and is under analysis now. It will provide further information.
Gusperimus (15-deoxyspergualin) inhibits mainly T-cell maturation and cytotoxic T-cell proliferation but also B cells. Two open label studies reported high response rates in refractory GPA. Administered in 28-day cycles of daily subcutaneous injection with washout periods, it has required close monitoring to avoid cytopaenias. The SPARROW trial (ClinicalTrials.gov number; NCT01446211) is evaluating the efficacy of gusperimus in relapsing and refractory GPA.
Plasma exchange is a treatment option for severe AAV. Confirmation of the pathogenicity of ANCA has contributed to a therapeutic rationale for plasma exchange in AAV, although removal of other factors may also be important. Meta-analysis of plasma exchange trials suggests a beneficial effect on the risk of end-stage renal disease but no effect on mortality. Current practice recommends plasma exchange for those presenting with severe renal disease or alveolar haemorrhage with little evidence supporting the latter indication. The ongoing PEXIVAS trial (ClinicalTrials.gov number; NCT00987389) is examining the effect of plasma exchange on patient and renal survival in those with a GFR below 50 ml/min or severe alveolar haemorrhage.
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