Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis.

Abstract

OBJECTIVE:

To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA).

METHODS:

The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other).

RESULTS:

Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare.

CONCLUSION:

Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3-ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.

• Authors: E M Miloslavsky, U Specks, P A Merkel, P Seo, R Spiera, C A Langford, G S Hoffman, C G M Kallenberg, E W St Clair, N K Tchao, L Viviano, L Ding, L P Sejismundo, K Mieras, D Iklé, B Jepson, M Mueller, P Brunetta, N B Allen, F C Fervenza, D Geetha, K Keogh, E Y Kissin, P A Monach, T Peikert, C Stegeman, S R Ytterberg, J H Stone, Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 65 Issue 9 Pg. 2441-9 (Sep 2013) ISSN: 1529-0131 [Electronic] United States
• PMID: 23754238 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 by the American College of Rheumatology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunosuppressive Agents
• Rituximab
• Cyclophosphamide
• Azathioprine

Topics

• Adult
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, therapeutic use)
• Azathioprine (administration & dosage, therapeutic use)
• Cross-Over Studies
• Cyclophosphamide (administration & dosage, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Granulomatosis with Polyangiitis (drug therapy)
• Humans
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Male
• Microscopic Polyangiitis (drug therapy)
• Remission Induction (methods)
• Rituximab
• Treatment Outcome