Long-term rituximab treatment safe, effective for IgG4-RD, new study finds
Off-label use of therapy shown to control disease regardless of regimen
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Long-term treatment with rituximab — a cancer drug used despite not having specific approval — is safe and generally effective for controlling IgG4-related disease (IgG4-RD), though researchers say more study is needed to standardize its use.
Those are the outcomes of a small study by scientists in Germany, who found that different rituximab dosing regimens appeared similarly effective in treating IgG4-RD. However, the team stressed a need for further research to better evaluate the optimal regimen.
“This study provides valuable insights into induction and long-term maintenance strategies for IgG4-RD, highlighting the efficacy and safety of long-term rituximab as well as the need for further research and standardization,” the scientists wrote.
Titled “Long-term treatment patterns and outcomes in IgG4-related disease — a retrospective single-center cohort study focusing on rituximab,” their report was published in the journal Rheumatology International.
IgG4-RD is a rare disorder marked by abnormal clumps of immune cells, particularly B-cells, that produce a type of antibody called IgG4. These abnormal cell clumps can result in tumor-like masses and swelling in virtually any part of the body, leading to a wide array of symptoms.
First treatment for IgG4-RD is glucocorticoids
First-line treatment for IgG4-RD usually involves glucocorticoids, which are powerful anti-inflammatory medications. However, such drugs can cause serious side effects with long-term use, and aren’t effective for all patients.
Administered intravenously, or directly into the bloodstream, rituximab (sold as Rituxan and MabThera, with biosimilars available) is a therapy that works by killing B-cells. It was originally developed to treat blood cancers in which B-cells grow out of control. In the past decades, however, it has also emerged as a treatment option for diseases like IgG4-RD that are driven by B-cells.
Although rituximab has never been formally approved for IgG4-RD, it is commonly used to help manage the disease, especially if glucocorticoids aren’t working. However, there isn’t an established protocol for how to dose the therapy in this patient population.
Generally, rituximab treatment involves a short course of frequent and/or high-dose infusions to get the disease under control — this is known as induction therapy. It’s typically followed by less frequent and/or lower-dose infusions, known as maintenance therapy, to keep the disease managed.
Although this general format is usually used in IgG4-RD, specific rituximab dosing regimens for induction and maintenance therapy can vary, and it’s not clear whether any particular regimen yields the best results, according to researchers.
Rituximab treatment drops relapses rates from over 80% to below 30%
In this study, scientists reported outcomes for 24 adults with IgG4-RD who were cared for at a specialty center in Munich. The patients were divided equally by sex, and their median age at diagnosis was 52. Slightly more than half had high blood IgG4 levels. Two-thirds had involvement of several organs, with the head and neck as the most commonly affected sites (in 42%).
Nearly all received initial treatment with glucocorticoids, and more than half (57%) went on to receive rituximab. Two patients started treatment with a combination of glucocorticoids and rituximab.
Among the 15 patients treated with rituximab, the median follow-up time after starting on the medication was longer than four years.
The most common induction regimen of rituximab consisted of four weekly infusions at a dosage of 375 mg per square meter of body surface area (m2), and the most frequent maintenance regimen consisted of one infusion at the same dose. Other patients received different dosage schedules, however. Most commonly, this was two 1 g infusions separated by two weeks for induction and/or maintenance treatment.
Most patients received 4-5 courses of rituximab, separated by six to 10 months.
“Median cumulative rituximab doses over two years did not differ significantly between regimens,” the researchers wrote.
All rituximab-treated patients showed a clinical response, regardless of the specific dosing regimen. The scientists noted that rates of relapse were generally high in the total patient population, affecting more than 80%. Relapses were more frequent after therapy discontinuation (25%) or during treatment with glucocorticoids alone (42.8%).
Importantly, the rate of relapses dropped from 86.7% before rituximab treatment to 26.7% while on rituximab. However, the time to relapse from the last treatment dose was shorter on rituximab than on previous induction treatment (median of five vs. 10 months).
“Our data confirm that rituximab induction regimen (4 × 375 mg/[m2] vs. 2 × 1 g) does not affect remission rates,” the researchers wrote. Further, the team noted that “maintenance with as little as 375 mg/[m2] is feasible, potentially reducing costs and side effects.”
Severe adverse effects were rare and further support the use of rituximab as maintenance therapy [for people with IgG4-RD].
Immunosuppressive therapies used for IgG4-RD, including rituximab, can increase the risk of infections. Infection rates were comparable among patients receiving rituximab or other immunosuppressive treatments. One patient died of severe infection complications shortly after undergoing induction treatment with rituximab, the data showed.
“Severe adverse effects were rare and further support the use of rituximab as maintenance therapy,” the researchers wrote.
Researchers: Future study needed for best practices
The scientists stressed that this study was limited to a small number of patients, and emphasized a need for further research on best practices for use of rituximab in IgG4-RD.
Nevertheless, their study “supports the current clinical use of rituximab for induction and maintenance treatment regardless of lacking [appropriately-controlled] trials, and at the same time highlights the need for further research and standardizations of treatment strategies,” the team concluded.
