MIAMI BEACH — B-cell depletion with rituximab may be a useful treatment option for severe refractory Wegener's granulomatosis when patients are intolerant or have a contraindication to cyclophosphamide, Dr. Ulrich Specks said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
Rituximab appears safe and effective for inducing and maintaining remission in patients with active severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Dr. Specks and colleagues at the Mayo Clinic, Rochester, Minn., reported.
In February, Genentech Inc. received an orphan product designation for rituximab (Rituxan) for the treatment of ANCA-associated vasculitis including Wegener's, microscopic polyangiitis, and Churg-Strauss syndrome.
In Dr. Speck and colleagues' prospective, open-label, industry-supported pilot trial, 10 patients with active disease received oral prednisone 1 mg/kg per day and four weekly infusions of rituximab 375 mg/m
Clinically, all patients went into complete remission by 3 months, and were tapered off prednisone by 5.5 months, Dr. Specks said. One patient experienced a clinical flare and was put back into remission after retreatment with rituximab and prednisone.
ANCA titers dropped in all patients, and generally did not rise until after B cell reconstitution. By 12 months, B cells had returned in 9 of 10 patients. “We didn't observe relapses in the absence of B cells and didn't observe relapses in the absence of ANCA-titer increases,” he said. Overall, the regimen was very well tolerated. There was only 1 infusion reaction, 1 case of influenza, 13 urinary tract infections in five patients, 2 herpes zoster cases, and no antichimeric antibodies developed.
Although the results compared well with earlier published small and single-case trials, larger studies should be conducted to determine whether rituximab should replace cyclophosphamide as the standard of care, he said.
While Dr. Specks gave rituximab a conditional nod, he noted that antitumor necrotic factor therapy provides no added benefit on top of standard therapy and should be avoided in patients who have received cyclophosphamide. He cited the high rates of adverse events, particularly the increased incidence of cancers observed in the Wegener's Granulomatosis Etanercept Trial, in which he was an investigator.