Rituximab found as effective for AAV survival as cyclophosphamide

But cyclophosphamide may be better for patients with kidney issues

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Treatment with rituximab has a similar efficacy to cyclophosphamide — both of them standard immunosuppressive therapies — in reducing short-time mortality in adults with life-threatening ANCA-associated vasculitis (AAV), a study in Japan found.

Moreover, rituximab was associated with a significantly lower risk of fungal infections relative to cyclophosphamide.

However, the therapy also was linked to a significantly higher risk of severe kidney disease, suggesting that rituximab may not be as effective at maintaining kidney health in patients.

These findings suggest cyclophosphamide might be preferred versus rituximab for inducing remission in people with life-threatening AAV complicated by rapidly progressive glomerulonephritis, or inflammation of the kidney’s filtering units, according to the researchers.

The study, “Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA associated vasculitis: a propensity score analysis of the real-world nationwide database,” was published in the journal Annals of Rheumatic Diseases.

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Investigating rituximab vs. cyclophosphamide in life-threatening AAV

AAV is characterized by inflammation and damage to small blood vessels, usually caused by ANCAs, which are self-reactive antibodies that bind to and overactivate neutrophils, a type of immune cell.

In severe cases, patients may experience life-threatening complications such as rapidly progressive glomerulonephritis — called RPGN for short — and/or alveolar hemorrhage, or bleeding in the lung’s tiny air sacs where gas exchange occurs.

Standard AAV treatment consists mainly of immunosuppressive therapies. Remission-induction treatment typically combines glucocorticoids, steroid hormones such as prednisone, with cyclophosphamide or rituximab.

While these combos have been shown to have comparable effectiveness in inducing disease remission, less is known about their safety and effectiveness in life-threatening cases of AAV.

Cyclophosphamide, sold under several brand names and with generics available, is an anti-cancer medication that works as an immunosuppressant. Rituximab, which promotes the death of antibody-producing immune B-cells, is sold as Rituxan in the U.S. and MabThera in Europe, with biosimilars available.

Both therapies can be given intravenously — rituximab  through infusions and cyclophosphamide directly into the bloodstream; cyclophosphamide also can be given orally.

Researchers in Japan now sought to compare rituximab versus cyclophosphamide using data obtained from a real-world nationwide inpatient database.

The team looked back at data from 687 adults with AAV and RPGN and/or alveolar bleeding who admitted to the hospital. All were treated with glucocorticoids plus rituximab or intravenous cyclophosphamide between 2018 and 2020.

The group of patients receiving rituximab had a significantly higher proportion of women (59% vs. 44.8%), and of hospitalizations in special functioning hospitals, such as university hospitals (38.5% vs. 28%), compared with the group of cyclophosphamide-treated patients.

The rituximab group also had significantly higher rates of chronic kidney disease (25.2% vs. 14.1%) and glucocorticoid pulse therapy at admission (36.2% vs. 31.6%).

On the other hand, these patients showed significantly lower rates of diabetes (28.2% vs. 39.3%) and smoking history (29.2% vs. 42.4%) relative to the cyclophosphamide group.

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No differences seen in mortality with rituximab vs. cyclophosphamide

In the analysis, no significant group differences were found regarding 30-day and 60-day in-hospital mortality. The team compared outcomes between 177 patients from each group who were matched for several demographic and clinical features.

However, the data showed that severe kidney dysfunction that required hemodialysis at discharge was significantly more frequent (8.5% vs. 2.4%) in rituximab-treated patients than among those given cyclophosphamide. A similar difference was found in the matched group of patients, but it did not reach statistical significance.

Hemodialysis is a procedure in which a patient’s blood is put through a filter called a dialyzer that removes extra water and waste outside the body, such as the kidneys.

In the matched group of patients, those treated with rituximab were twice as likely to have severe kidney impairments in the short term as were those on cyclophosphamide.

There were no significant group differences regarding the overall rate of infection in all patients. However, fungal infections were significantly less common among rituximab-treated patients (6.4% vs. 15.5%) while infections by the cytomegalovirus were significantly more common in this group (18.4% vs. 11.7%).

Among the matched group of patients, those in the rituximab group had a 55% significantly lower probability of having a fungal infection and were 42% less likely to have pneumonia caused by the Pneumocystis jirovecii fungus than those on cyclophosphamide.

In turn, patients treated with rituximab had a 53% higher chance of having a cytomegalovirus infection, but this difference was not statistically significant.

“In life-threatening AAV, [rituximab] has similar short-term effectiveness on mortality to [intravenous cyclophosphamide],” the researchers wrote.

They added, however, that “the short-term renal prognosis might be inferior to [intravenous cyclophosphamide].”

Overall, the study comprised “one of the largest numbers of cases ever registered and [analyzed] in a clinical study of AAV,” the team wrote, considering it a major strength of the study.

Future appropriately-controlled clinical trials and studies following patients over time are needed to confirm the results.