Long-term IgG4-RD control possible with azathioprine treatment: Study
Use of immunosuppressive medication in real world helped cut steroid need
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Azathioprine, an immunosuppressive medication, may help keep immunoglobulin G4-related disease (IgG4-RD) under control over the long term, while reducing glucocorticoid, or steroid, use, according to a small real-world study in Austria.
In most of the 10 patients evaluated, azathioprine — primarily used to treat immune diseases — was associated with stable remission, or the easing or disappearance of symptoms, for as long as 13 years, the researchers noted. Overall, the individuals in this study used the medication as a maintenance therapy for an average of nearly four years, the data showed.
Also, no patient needed additional glucocorticoids, a standard IgG4-RD treatment linked to serious side effects when used over long periods, the team noted.
“This study provides valuable real-world data on azathioprine use in patients with IgG4-RD,” the researchers wrote. “Given the limited existing research on azathioprine as maintenance therapy in IgG4-RD, our findings add information on safety and risk of relapse of azathioprine.”
The study, “Azathioprine as maintenance therapy for IgG4-related diseases: a retrospective case series and case-based review of the literature,” was published in the journal Rheumatology International.
IgG4-RD, which affects men more commonly than women, occurs when immune cells, mainly B-cells that produce a type of antibody called IgG4, infiltrate tissues. This can cause inflammation and tissue scarring in multiple tissues and organs, which drive IgG4 symptoms.
Glucocorticoids, or steroids, are a cornerstone of IgG4-RD treatment
Glucocorticoids, part of a class of steroid hormones, are generally recommended as the first-line treatment to induce disease remission in people with symptomatic IgG4-RD.
However, such medications are associated with serious side effects when used long-term or at high doses. Further, according to the researchers, at least one-third of patients and as many as 53% experience relapses after glucocorticoid tapering, or reductions in use.
“To minimize relapse risk and [glucocorticoid-associated] toxicity, [glucocorticoid-sparing] immunosuppressive therapies are employed,” the researchers wrote.
This includes azathioprine, the team noted. However, there is “insufficient data regarding [azathioprine] safety profile, optimal treatment duration, and organ-specific efficacy,” the researchers wrote.
To learn more, the team, from the Medical University of Graz in Austria, retrospectively analyzed data from 10 men with IgG4-RD treated with azathioprine at their institution and followed for at least nine months.
The patients had a mean age of 59.4 at disease onset (range, 32-78). They were followed for an average of 75.2 months, or more than six years, and for as long as 14 years. More than half (60%) had disease involvement affecting a single organ, while the remaining four patients (40%) had two or more affected organs.
The most affected organs were lymph nodes, which are immune structures throughout the body, in 50%, and the pancreas, in 40%. For 30%, the retroperitoneal tissue, or the area in the back of the abdomen where several tissues and organs are located, including the kidneys, was affected.
All had received glucocorticoids, and the most common reason for starting azathioprine was, for 70%, the intention to reduce glucocorticoid exposure. Other reasons for starting the immunosuppresive medication were relapses under glucocorticoid therapy and glucocorticoid side effects.
The treatment was initiated about one year after diagnosis and lasted a mean of 45.8 months , or nearly four years, and as long as 13 years. The average starting dose was 175 mg/day.
7 of 10 patients on azathioprine remained in remission
Most participants (70%) remained in remission throughout follow-up, while three (30%), including the two patients with kidney involvement, experienced a total of five relapses while on azathioprine. Overall, weight-adjusted azathioprine doses were lower in those who remained in remission than in those who experienced relapses.
At the last follow-up, five patients (50%) were still on azathioprine alone. Two had switched to rituximab, a targeted immunosuppressive therapy sold as Rituxan and MabThera, with biosimilars available, and one of them became free from any immunosuppressive treatments after achieving sustained remission. Three other participants were also no longer receiving immunosuppressive therapy.
Azathioprine was discontinued due to relapses in two people, blood abnormalities in three cases, and patient preference in one person.
Azathioprine may be a potentially effective and well-tolerated option for maintenance therapy in patients with IgG4-RD, with a favorable safety profile.
Regarding blood biomarkers, IgG4 levels were persistently higher in participants who subsequently relapsed under azathioprine. Elevated levels of C-reactive protein (CRP), a marker of inflammation, were also mainly seen in those who later relapsed, “suggesting that CRP may serve as a potential risk marker for relapses,” the researchers wrote.
Adverse events reported while on azathioprine were blood abnormalities, including low counts of certain blood cells, infections, and elevated liver enzymes, which can be indicative of potential liver damage.
The researchers concluded that “azathioprine may be a potentially effective and well-tolerated option for maintenance therapy in patients with IgG4-RD, with a favorable safety profile.”
Still, the team noted that “larger, randomized studies are needed to confirm these observations and to better define optimal maintenance strategies.”
