Real-world data support rituximab for treating IgG4-RD, cutting steroid use
Off-label therapy works about as well as glucocorticoids, even for severe disease
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Rituximab appears to control immunoglobulin G4-related disease (IgG4-RD) about as well as glucocorticoids but allows patients to use lower doses of this type of corticosteroid — a class of steroid hormones — overall, which may prevent serious side effects, according to a large real-world study in Europe.
“Our real-world data support the growing body of evidence supporting the glucocorticoid sparing effect of rituximab, even among patients with more severe and relapsing IgG4-RD,” the researchers wrote.
Overall, according to the team, “this multi-center study supports the use of rituximab in patients with IgG4-RD.”
The study, “Rituximab limits glucocorticoid use in IgG4-related disease: Real-world evidence from a large European cohort,” was published in the European Journal of Internal Medicine.
IgG4-RD occurs when immune cells, mainly B-cells, infiltrate tissues and cause long-lasting inflammation in different organs, leading to a range of symptoms. The standard treatment has usually been off-label glucocorticoids such as prednisolone that reduce inflammation by broadly suppressing immune activity. However, long-term use of these steroid medications can cause serious side effects.
Rituximab use for IgG4-RD increasing, per researchers
Rituximab, marketed as Rituxan in the U.S. and Mabthera in Europe (with biosimilars available), works by depleting B-cells. While it is not approved to treat IgG4-RD, “rituximab is increasingly used off-label,” the researchers wrote.
To learn more about its use, an international team of researchers looked at real-world data from 167 adults with IgG4-RD who were followed at three European centers. Three-quarters of the patients were men. The goal of the analysis was to assess rituximab’s glucocorticoid-sparing effects.
Altogether, slightly more than two-thirds of patients were treated with rituximab — 75% alongside glucocorticoids and 25% without those drugs — while nearly one-third were given glucocorticoids alone
Patients in the rituximab group were significantly younger than those on glucocorticoids alone (56.2 vs. 63.7 years) and had lived with the disease for a significantly longer period (about three vs. 1.5 years).
Those given rituximab also had significantly higher scores on the IgG4-RD responder index, a measure of disease severity (5.6 vs. 4.3), and were significantly more likely to have relapsing disease (71.3% vs. 9.6%), according to the data.
These findings suggest that the rituximab group started out with more difficult disease to control. Despite this, rituximab was linked to better glucocorticoid-sparing effects, the researchers noted.
After six months, almost half of those in the rituximab group were able to stop glucocorticoids completely, compared with a much smaller proportion in the glucocorticoid-only group: 48% of patients versus 14%.
Patients had 3.5 times higher chance of being steroid-free at 6 months
Statistical analyses adjusted for potential influencing factors showed that patients on rituximab had more than 3.5 times higher odds of being glucocorticoid-free at six months.
At one year, a higher proportion of patients on rituximab were free from glucocorticoids (53% vs. 35%). However, adjusted statistical analyses found no significant difference between the groups in terms of odds of being glucocorticoid-free. Still, the total median daily dose of oral prednisolone used within one year was significantly lower in the rituximab group (1,640 vs. 2,950 mg), the data showed.
In terms of disease control, both treatments worked similarly, with about 80% of participants responding to treatment and about one-quarter achieving remission, or no signs or symptoms of disease.
A lower proportion of patients on rituximab experienced a disease relapse in the first six months of treatment (9.6% vs. 17.3%), but this difference didn’t reach statistical significance, meaning it may be due to chance.
Safety outcomes were also similar, with infections serious enough to require hospital care occurring at similar rates in both groups, the researchers noted.
Most patients in the rituximab group received two infusions at the start of treatment, and more than 60% received maintenance rituximab treatment six months later to maintain disease control.
A small number of these patients used other immunosuppressive medications, the data showed. Some participants who received maintenace rituximab had signs of more active disease at six months, suggesting that doctors tended to re-treat those who were not doing as well or who had early signs of relapse.
“In this multi-center European real-world study, patients in the rituximab group had features of more severe IgG4-RD compared to patients in the glucocorticoid group,” the researchers wrote. “Nevertheless, efficacy [measures] were similar in both groups, and patients in the rituximab group were more likely to be free from glucocorticoids at follow-up.”
According to the researchers, “this is the largest study investigating rituximab compared to glucocorticoids for IgG4-RD” conducted to date.
