Study: Rituxan Reduces Disease Activity in EGPA, But Relapses Stay High

Study: Rituxan Reduces Disease Activity in EGPA, But Relapses Stay High

Treatment with Rituxan (rituximab) had some efficacy in eosinophilic granulomatosis with polyangiitis patients, leading to a reduction in glucocorticoid requirement, but asthma and ear, nose and throat (ENT) relapse rates remained high despite continued treatment, a study found.

The study, “Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis,” was published in the journal Rheumatic & Musculoskeleal Diseases.

ANCA-associated vasculitis (AAV) is a disease characterized by inflammation and damage to medium-sized and small blood vessels.

There are three major AAV subtypes — granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) — each with their own disease mechanisms, clinical features, and treatment responses.

EGPA is normally associated with asthma and elevated levels of eosinophils, a kind of immune cell. Its management currently relies on glucocorticoids and immunosuppressive agents, but relapses and high glucocorticoid exposure in this patient population are quite frequent.

Rituxan is an anti-CD20 antibody approved for remission induction and maintenance in GPA and EGPA patients. However, there is a lack of data surrounding the effectiveness of Rituxan in EGPA patients.

Aiming to answer that question, a group of European researchers studied EGPA patients who had received Rituxan treatment. The patients were either non-responsive to standard treatment or unable to receive cyclophosphamide (an immunosuppressive treatment) because of contraindications.

The study included 69 patients who received Rituxan between 2003 and 2017. Most (44) were female; the median length of treatment was 23 months.

Response to therapy was determined every three months over a two-year period. Response to treatment was defined as a Birmingham Vasculitis Activity Score (BVAS) — a validated measure of disease activity — of zero, independent of glucocorticoid dose. Partial response was defined as a 50% or greater reduction in BVAS from baseline.

At six months of Rituxan treatment, 76.8% of patients had experienced an improvement, determined by either response or partial response. The rates increased to 82.8% at one year and 93.2% at year 2.

Overall, the median BVAS decreased from 6 at baseline to 1 at six months, and zero at one and two years. Thus, Rituxan was effective in reducing disease activity of EGPA.

The excess use of glucocorticoids is linked to significant side effects, including an increased risk of cardiovascular problems, bone and muscle wasting, eye problems, gastrointestinal problems, and increased risk of infections. Thus, it is important that treatments for AAV allow patients to reduce their daily dose of glucocorticoids.

In this study, researchers reported that the daily dose of prednisolone decreased from a median of 12.5 mg to 7 mg at six months, 7.5 mg at one year, and 5 mg at two years.

Unfortunately, relapses had occurred in 54% of patients by two years, with asthma being the most frequent manifestation.

Patients who were positive for ANCA antibodies benefited the most from Rituxan, as they experienced a longer time to any asthma/ENT relapses, as well a shorter time to remission.

“Rituximab demonstrated some efficacy in EGPA and led to a reduction in prednisolone requirement, but asthma and ENT relapse rates were high despite continued treatment. The ANCA- positive subset appeared to have a more sustained response on isolated asthma/ENT exacerbations,” investigators concluded.

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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