Rituximab successfully re-induces remission after ANCA-associated vasculitis relapse
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Rituximab, used alongside glucocorticoids, is highly efficacious in re-inducing remission among relapsed patients with ANCA-associated vasculitis, according data published in Annals of the Rheumatic Diseases.
“Prior to the availability of effective treatment, AAV had a mortality of 93% within 2 years, primarily due to renal and respiratory failure,” Rona M. Smith, MD, MRCP, of the University of Cambridge, and colleagues wrote. “The introduction of glucocorticoids and cyclophosphamide, which became established treatment for this disease in the 1980s, markedly improved survival, inducing remission at 1year in approximately 80% of patients.”
“However, relapsing disease is common with over 50% of patients experiencing a relapse within 5years and the majority suffering treatment-related toxicity,” they added. “... The optimal strategy to maintain remission following induction of remission with rituximab, especially for treatment of relapse, is not clear.”
To assess rituximab (Rituxan; Genentech, Biogen) and glucocorticoids as therapy to induce remission in patients with ANCA-associated vasculitis who have relapsed, Smith and colleagues analyzed a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. According to the researchers, RITAZAREM was an international, multicenter, open-label, randomized, controlled study designed to determine whether rituximab was superior to azathioprine for remission maintenance, following the induction of remission using rituximab and glucocorticoids, among relapsed patients with ANCA-associated vasculitis.
For the induction phase of the trial, during months 0 to 4, eligible patients aged 15 years and older were enrolled at the time of relapse and received four weekly rituximab doses of 375 mg/m2 plus glucocorticoids. The glucocorticoid regimen was dictated based on physician choice, and was reduced from either 1 mg/kg per day or 0.5 mg/kg per day to 10mg per day by month 4. Baker and colleagues included 188 participants in their analysis. They later randomly assigned patients who achieved remission receive one of two regimens to prevent relapse.
According to the researchers, 63% of patients who relapsed demonstrated at least one major disease activity item, while 29% received the higher dose glucocorticoid regimen. In all, 90% of patients achieved remission by 4 months, and just six patients failed to achieve disease control by that time. Four patients died during the induction phase due to pneumonia, cerebrovascular accident or active vasculitis. Investigators observed 41 severe adverse events in 27 patients, including 13 severe infections.
“These data from the induction phase of the RITAZAREM trial, the largest reported prospective cohort of patients with relapsing AAV, demonstrate that rituximab, in conjunction with glucocorticoids, is effective at re-inducing remission in patients with AAV who have relapsed, regardless of previous therapy,” Smith and colleagues wrote. “A high proportion of patients (171/188, 90%) achieved remission by 4 months, and it is notable that 71% of patients received the lower dose glucocorticoid regimen.”
“Although there are retrospective series, the only previous prospective data on induction of remission for this subgroup of patients with ANCA-associated vasculitis was from the RAVE trial that observed a higher rate of remission in 50 relapsing patients treated with rituximab when compared with 50 relapsing patients treated with cyclophosphamide,” they added. “Thus, these data confirm and extend the data on the efficacy of rituximab for relapsing [granulomatosis with polyangiitis/microscopic polyangiitis] and supports a recommendation of rituximab for this indication.”
Perspective
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David A. McLain, MD, FACP, FACR
Rituximab has been a very versatile medication since its approval in November 1997. It was the first monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for treatment of lymphoma.
In the rheumatology world, rituximab is FDA approved for rheumatoid arthritis and adult patients with AAV, such as granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), in association with glucocorticoids. Off-label, rituximab is being used for Felty’s syndrome, immune thrombocytopenia, systemic lupus erythematosus, autoimmune hemolytic anemia, macroglobulinemia, multiple sclerosis, myasthenia gravis and bullous dermatoses, among others.
The present investigation of the relapse phase of the AAV RITAZEREM study looked at reinduction of remission after relapse. The rituximab dosage at relapse was 375 mg/m2 IV weekly for 4 weeks; this was also the induction dose at the beginning of this investigation, while the maintenance dosing was 1000 mg IV every 4 months. There were two glucocorticoid regimens, a 60 mg per day group and a 30 mg per day group, which both tapered to 10 mg per day by the fourth month.
The researchers found that 71% of those who achieved remission received the 30 mg/d dose. This study demonstrated induction in remission in 90% of patients by 4 months with rituximab alone. This is the only prospective study to show that rituximab is effective to induce remission after relapse in AAV, which is certainly very helpful for us as we care for these patients.
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