Treating ANCA-associated vasculitis with rituximab tied to HGG risk
Higher glucocorticoid doses also raised chance of low antibodies, infections
ANCA-associated vasculitis (AAV) patients treated with rituximab are up to four times more likely to develop hypogammaglobulinemia (HGG), or low blood levels of antibodies that help fight off infections, than people with other autoimmune conditions.
That’s according to a real-world study in China that also found that higher doses of glucocorticoid maintenance treatment increased the chances of HGG and severe infections with autoimmune conditions, including AAV. Specifically, a 7.48 mg daily dose of prednisone, a glucocorticoid, was identified as a safe threshold dose to avoid severe infections with rituximab. Coexisting chronic lung disease was also significantly associated with a greater risk of severe infections.
This means patients “who have chronic lung disease or who are receiving [at least 7.5 mg/day] of prednisone during [rituximab] treatment warrant increased attention because of their vulnerability to infection,” the researchers wrote.
The study, “Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience,” was published in the Journal of Clinical Immunology.
Autoimmune conditions, including AAV, are typically associated with self-reactive antibodies being produced that attack the body’s healthy cells and molecules.
Rituximab, sold as Rituxan and others, with available biosimilars, works by killing B-cells, which are responsible for producing not only the antibodies that help the body fight invaders, but the self-reactive antibodies that drive autoimmune diseases. By reducing B-cell levels, the therapy should help suppress the production of self-reactive antibodies and reduce symptoms of autoimmune conditions.
Rituximab is approved for treating certain blood cancers and autoimmune conditions, including AAV and rheumatoid arthritis. It’s used off-label for a number of other autoimmune diseases, but its B-cell-depleting effects mean people taking it are at risk of HGG, which may reduce their natural immune response and increase the risk of severe infections.
HGG with rituximab treatment
Here, researchers in China sought to determine the frequency and predictors of HGG and severe infections with rituximab treatment in adults with autoimmune conditions, including AAV, in a real-world setting.
Given that rituximab is often used with glucocorticoids, a standard immunosuppressive treatment, the researchers looked specifically at possible links between a glucocorticoid maintenance dose and risk of HGG and severe infections. They retrospectively analyzed data from 219 patients (69.4% women) treated with rituximab at their center between January 2013 and January 2023.
Regarding the type of autoimmune disease, 117 adults had connective tissue diseases, which include lupus and systemic sclerosis, 75 had AAV, and 27 had IgG4-related disease.
HGG occurred in 63.3% of the patients and most commonly affected IgM and IgG, two types of antibodies involved in primary and secondary immune responses, respectively. The levels of these antibodies showed a significant decline three months after rituximab was started.
AAV patients had a significantly higher chance of developing HGG with rituximab than the other two groups. Specifically, adults with AAV were 4.5 times more likely to have low IgG levels, twice as likely to show low IgM levels, and three times more likely to have low levels of IgA levels, a type of antibody involved in protecting the body’s mucus-covered membranes.
Risk of infections
Forty-nine episodes of severe infection were reported among all the patients. This corresponded to about seven events per 100 person-years, indicating 7 of 100 patients had an infection in one year.
The most common infection was pneumonia, a type of serious lung infection (63.2%), followed by sepsis, which is a generalized, exaggerated immune response (12.2%), and urinary tract and gastrointestinal infections (10.2% each).
Statistical models showed that a longer disease duration and higher IgG levels at the start of treatment were protective factors against HGG, and were linked to an up to 15% lower chance of it. In turn, a maintenance glucocorticoid dose of 5mg/day or higher combined with rituximab was independently associated with a 7% greater chance of HGG.
Also, simultaneously having interstitial lung disease or bronchiectasis, two chronic lung conditions, was significantly linked to a fourfold higher chance of severe infections and a high glucocorticoid maintenance dose increased the risk by 6%. Higher numbers of CD3-positive T-cells, a type of immune cell, at the start of treatment was associated with a 37% lower likelihood of severe infections.
The higher the glucocorticoid maintenance dose, the greater the chance of severe infection, with a dose of at least 7.5 mg per day of prednisone, or an equivalent, being significantly associated with a higher risk, further analysis indicated.
The findings “help to provide practical guidance for safety monitoring of [rituximab] in routine care for [autoimmune disease] patients,” the researchers wrote.
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