A combination treatment with Rituxan (rituximab), low-dose cyclophosphamide (Cytoxan), and tapered corticosteroids induces significant disease remission and reduces risk of relapse in patients with ANCA-associated vasculitis (AAV) with renal symptoms, U.K. researchers found.
The study, “Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis,” appeared in the journal Nephrology Dialysis Transplantation.
Depletion of B-cells (a type of immune cell) with Rituxan became an established strategy to induce and maintain remission in AAV. The medication was initially described as add-on therapy to conventional treatment, but results of two clinical trials showed that Rituxan was not inferior to the immunosuppressant cyclophosphamide in AAV, which led to its approval for this disease in 2011. Recent results suggest that Rituxan is also effective in preventing disease relapse.
Despite international guidelines supporting the use of Rituxan as an alternative to cyclophosphamide in patients with organ- or life-threatening disease, including those with renal complications, few studies evaluated the benefit of combining Rituxan with cyclophosphamide.
The scarcity of available data indicates that combined or sequential treatment with the two medications in kidney disease is safe and extends the time until relapse, compared to Rituxan alone.
The research team has been using a combination of Rituxan, low-dose intravenous cyclophosphamide, and oral corticosteroids since 2006 to induce remission in renal AAV. The use of Rituxan was intended to reduce the dose of cyclophosphamide.
Then, after the initial combination therapy, patients took a maintenance regimen with the immunosuppressive azathioprine and tapered steroid.
Earlier results with this approach in 23 patients demonstrated high rates of remission and extended relapse-free survival. Researchers now present the results of their extended experience with this treatment strategy in a larger group (66 patients) who were followed for a median of four years and eight months.
Long-term differences in relapse-free, renal and patient survival were compared with 198 matched cases from the European Vasculitis Study Group (EUVAS) trials.
At six months, 94% of patients had achieved disease remission. At year two, 84% of patients had no detectable ANCA antibodies and 57% remained depleted of B-cells. This contrasted with findings in other studies, which revealed increases in B-cell levels at 12 months.
At five years, 70% percent of these patients had not relapsed. Patients with sustained ANCA negativity and B-cell depletion were less likely to relapse, researchers found.
The treatment also showed a 71% decreased risk of death, an 80% lower risk of worsening to end-stage renal disease, and a 51% reduced risk of relapse compared to patients from the EUVAS trials.
“Relapse rates were lower than expected compared with previously published cohorts treated with purely cyclophosphamide-based regimens,” the investigators noted.
Among the study’s limitations, the investigators mentioned not having evaluated the treatment in patients with severe disease manifestations and not having more patients with relapsing disease at enrollment.
The results showed that “this regimen is potentially superior to current standards of care,” researchers wrote.
“We propose that prospective studies are desirable to compare the use of this regimen, and other B-cell-depleting strategies, with current standard treatment protocols,” they added. Additional studies are also needed “to establish if this regimen may provide the basis for further corticosteroid avoidance in the management of renal AAV.”