Long-term steroid OK for RA but challenges guidelines

Contrary to what current guidelines advocate, long-term use of corticosteroid works fine in older patients with rheumatoid arthritis (RA), suggests the much-anticipated GLORIA* trial presented at EULAR 2022.

“Most experts agree that long-term glucocorticoid therapy is harmful,” said study author Dr Maarten Boers from Amsterdam University Medical Center, Amsterdam, the Netherlands. “Existing guidelines actually suggest avoiding glucocorticoid or using it only as ‘a bridging’ therapy with conventional synthetic DMARDs**, at the lowest dose and for the shortest time possible.”

Nevertheless, such opinions are based on observational studies with high potential bias, added Boers. “The limited data from trials (mostly in early RA) do not support strong claims of harm, and their generalisability is questioned.”

Glucocorticoids in RA have the advantage of a rapid onset of action, which allows waiting for the onset of csDMARDs. However, the benefit/risk ratio of glucocorticoids remains precarious and their modalities of use in RA remain controversial.

In the GLORIA trial, RA patients aged 65 and older who were treated with low-dose (5 mg/day) prednisolone – a glucocorticoid – for 2 years achieved significantly greater reductions in disease activity, as measured by the 28-joint disease activity score (DAS28) and the American College of Rheumatology (ACR) response criteria vs those assigned to placebo.

Patients in the trial  (n=451) had a mean of two comorbidities, with an RA duration of 11 years on average. DAS 28 was 4.5 points and 90 percent had joint damage. Seventy-nine percent of the patients were on DMARDs (mostly methotrexate), and 14 percent were on biologic agents. Patients were randomized 1:1 to prednisolone or to placebo and remained on other RA therapies their clinicians prescribed as appropriate. [EULAR 2022; abstract OP0263]

Benefits persist for up to 2 years

Within 3 months, mean DAS28 scores, which is one of the primary outcomes, fell markedly in both the prednisolone and placebo groups, but the magnitude was greater with prednisolone and stayed through the 2 years trial.

At the final follow-up, the mean DAS28 score was lower by 0.37 points with prednisolone vs placebo (p<0.0001), reported Boers. There was also less joint space narrowing with prednisolone vs placebo (mean 0.2 vs 1.2 points by Sharp/van der Heijde score), with fewer erosions (mean 0.1 vs 0.7), for a significant mean difference of 1.7 points in favour of prednisolone.

Response rates by ACR criteria were as follows: ACR20 (53 percent with prednisolone, 33 percent with placebo), ACR50 (30 percent with prednisolone, 13 percent with placebo), ACR70 (12 percent with prednisolone, 2 percent with placebo).

Rates of adverse event rates were similar between groups except for infections, which occurred at rates of 42 per 100 patient-years with prednisolone vs 30 with placebo, but they were mostly mild to moderate in severity. Rates of discontinuation were also similar in both groups.

“Add-on low-dose prednisolone at 5 mg/day for up to 2 years has beneficial effects in senior RA patients, with a trade-off of a 24-percent increase in the proportion of patients with mostly non-severe adverse events,” Boers said in summing up the GLORIA findings. “There’s a favourable balance of benefit and harm. With proper monitoring, titrating around this level will allow optimum suppression of disease activity.”

In current practice, many RA patients are chronically treated with low-dose glucocorticoids, in direct contradiction with guidelines. “Our study adds substantial evidence to support practice rather than guidelines,” he added.

Time to revisit guidelines

Until GLORIA, long-term use of steroids had not been tested in an adequately powered, randomized, placebo-controlled trial. The current guidelines on RA need to be revisited with GLORIA's positive results, pointed out Boers.