Prolonged disease-free remission following rituximab and low-dose cyclophosphamide therapy for renal ANCA-associated vasculitis.

Abstract

BACKGROUND:

Rituximab (RTX) has been shown to be effective as an induction agent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but studies have been limited by short-term follow-up. We decided to investigate the long-term efficacy and safety of an RTX-based cyclophosphamide (CYP)-sparing regimen (CycLowVas) for renal AAV.

METHODS:

Consecutive patients with renal AAV presenting de novo or with a major relapse, except those with serum creatinine >500 μmol/L, previous treatment with RTX and pulmonary haemorrhage or cerebral vasculitis, were treated with two pulses of RTX 2 weeks apart and six fortnightly doses of CYP, as well as a reducing protocol of daily oral steroids. Maintenance was with low-dose steroids and azathioprine.

RESULTS:

Twenty-three patients were treated. Median follow-up was 39 months, with 17 patients reaching >2 years of follow-up. All patients achieved clinical remission within 6 weeks. Three major and two minor relapses occurred in five patients at a median of 30 months, which were treated by re-dosing with RTX for major relapses and steroid increase alone for minor relapses. Adverse events included one severe drug reaction, four non-serious and one serious infective episodes in the first 3 months, one skin malignancy at 21 months and one death at 19 months not related to treatment or disease.

CONCLUSIONS:

A RTX-based low-dose CYP regimen is effective at inducing long-term disease-free remission and may be the platform on which to develop a steroid-minimizing regimen to further decrease adverse events in the future.

• Authors: Nicholas Mansfield, Sally Hamour, Anne-Marie Habib, Ruth Tarzi, Jeremy Levy, Megan Griffith, Tom Cairns, H Terence Cook, Charles D Pusey, Alan D Salama
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 10 Pg. 3280-6 (Oct 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 21414973 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Rituximab
• Cyclophosphamide

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (drug therapy)
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cyclophosphamide (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Kidney Diseases (drug therapy)
• Male
• Middle Aged
• Prospective Studies
• Remission Induction
• Rituximab
• Treatment Outcome
• Young Adult