Rituxan Combo Returns ANCA-associated Vasculitis Patients to Remission, Phase 3 Trial Shows
The RITAZAREM trial dealt with relapses of anti-neutrophil cytoplasmic antibody-associated vasculitis, whose shorter name is ANCA-associated vasculitis, or AAV.
Genentech presented the study’s preliminary findings at the 2017 ACR/ARHP Annual Meeting in San Diego, Nov. 3-8. The presentation was titled “Rituximab As Re-Induction Therapy in Relapsing ANCA-Associated Vasculitis.”
U.S. and European regulators have approved a combination of Rituxan and glucocorticoids to bring about remission in two AAV subtypes, granulomatosis with polyangiitis, or GPA, and microscopic polyangiitis, MPA.
Despite its benefits, at least half of patients who use it develop symptoms again within two years. Finding ways to keep AAV under permanent control has become a major concern of doctors and patients.
A Cambridge University study suggested that treating patients with Rituxan every six months prevents the disease from returning. Genentech decided to conduct a trial (NCT01697267) to compare Rituxan and azathioprine as maintenance therapies for patients who used Rituxan and glucocorticoids to achieve remission in the first place.
The company is conducting the ongoing trial — the largest study of Rituxin in relapsing AAV patients — at more than 30 clinical centers worldwide. A European Vasculitis Study team and the Vasculitis Clinical Research Consortium designed the trial.
The study involves 188 people who had had relapsing GPA or MPA a median of five years. They achieved remission by taking a combination of Rituxan and glucocorticoids for up to four months.
Researchers then randomized them to receive either Rituxan or azathioprine every four months for two years. They will follow the patients for four years.
The preliminary findings that Genentech reported cover the trial’s four-month initial treatment phase.
Seventy-three percent of the patients had autoantibodies for GPA and 37 percent for MPA. Researchers said 79 percent had received cyclophosphamide and 36 percent Rituxan before the trial.
Among the 181 patients available for analysis, 165, or 91 percent, achieved remission by month four.
Of the 11 who failed to achieve it, nine had GPA, nine had ear, nose, and throat problems before the trial started, seven had a severe form of the disease before the study began, and nine had received low-dose glucocorticoids.
Five patients died in the trial’s initial treatment phase, two of pneumonia, one of a brain accident, one of respiratory failure, and one of colon cancer.
During the trials 53 patients experienced severe adverse events. The most common were infections.
“Rituximab, in conjunction with glucocorticoids, is highly effective at re-inducing remission in patients with relapsing ANCA-associated vasculitis, with an acceptable safety profile,” the researchers concluded.