medwireNews: Findings from the GLORIA trial suggest that older patients with established rheumatoid arthritis (RA) could benefit from 2 years of low-dose glucocorticoids (GC) in addition to their existing disease-modifying treatment with a favorable balance of benefit and harm.
The trial findings, which were reported in two presentations at the EULAR 2022 Congress in Copenhagen, Denmark, also indicate that GCs can be successfully tapered after 2 years, with only moderate increases in disease activity and flare risk and no evidence of adrenal insufficiency.
“Most experts agree that long-term GC therapy is harmful, and existing guidelines suggest to avoid or use GC only as ‘bridging’ therapy; however, such opinions are based on observational studies with high potential for bias,” note Maarten Boers (Amsterdam UMC Locatie VUmc, the Netherlands) and co-researchers, whose research was simultaneously published in the Annals of the Rheumatic Diseases.
“The limited data from trials (mostly in early RA) do not support strong claims of harm, but their generalisability is questioned.”
With this in mind, the team conducted a large pragmatic, randomized trial of 2 years of add-on treatment with the GC prednisolone 5 mg/day or placebo in 451 patients with established RA aged an average of 72 years and with a mean 2.1 comorbidities. Their disease duration was 11 years on average, they had a mean DAS28 of 4.5 points, and 90% had joint damage. The majority (79%) of patients were on disease-modifying treatment, which included 14% on biologics.
In all, 63% of the patients assigned to prednisolone completed the trial, compared with 61% of those in the placebo group, and rates of discontinuation were similar in both groups.
Disease activity declined in both treatment groups during the first 3 months of treatment and stabilized at 1 year. Over the 2 years of treatment, the 224 patients taking prednisolone had a significant 0.37-point lower DAS28 score, on average, than the 225 taking placebo.
The researchers say that this difference “may appear modest” but point out that the 3-month results in a group of 304 per-protocol patients, who did not receive GC injections and did not switch treatment, suggest a more substantial benefit, with a significant 0.62-point lower DAS28 with prednisolone.
Also, the benefit of prednisolone on disease activity was consistent across response indices and for the achievement of minimal disease activity and remission, the researchers point out.
There appeared to be a smaller effect of prednisolone over the second year of treatment, which Boers and colleagues explain could be because “physicians were allowed to continuously optimise treatment, confounding the comparison.”
Prednisolone treatment was also associated with less joint damage progression as measured by the Sharp/van der Heijde score, with a significant mean difference of 1.7 points in favor of the treatment, and a greater distribution of patients with negative or zero progression versus those with any or clinically relevant progression.
The investigators highlight that there was a “trade-off” to prednisolone’s benefit on disease activity in terms of a 24% increased risk of having at least one adverse event of special interest, including serious events, GC-specific events (such as cardiovascular events, infections, and symptomatic bone fracture), and those causing study discontinuation.
These occurred in 60% of prednisolone-treated patients versus 49% of those given placebo, with the difference primarily due to infections (26 vs16%), which were mostly mild to moderate in severity.
“Although of concern, these should be interpreted in the light of the high-risk trial population, resembling patients in clinical practice,” highlight the study authors. They suggest that “the risks of low-dose GC are not of special concern but should be viewed through the same lens as those of other DMARDs.”
The team notes that “[i]n current practice, many patients with RA are chronically treated with low-dose GC, in direct contradiction with guidelines,” and adds: “Our study adds substantial evidence to support practice rather than guidelines.”
Tapering of GC after 2 years of treatment
Findings from the GLORIA trial also showed it is feasible to taper GC following the 2 years of prednisolone treatment to zero in 3 months by adding a stop day every 2 weeks, said Abdullah Almayali (Vrije Universiteit, Amsterdam, the Netherlands) who presented the findings.
He reported that among 80 patients taking prednisolone, who successfully completed the GLORIA trial and did not require GC in the 4 weeks after the final trial visit, tapering of GC resulted in a significant 0.3-point increase in DAS28, from 2.9 points at the final trial visit to 3.2 points.
Almayali noted that this still reflected “low disease activity levels” and was similar to the mean 3.1 points achieved by 85 placebo-treated patients at the final trial visit, for whom DAS28 disease activity remained stable with GC tapering, giving a treatment difference of 0.21 points.
Disease flares occurred in 44% of 99 evaluable patients in the prednisolone group, as determined by a DAS28 increase of more than 0.6 points or the need for GC between week 5 and 12 of taper. This compared with 31% of 100 patients given placebo, giving a nonsignificant 43% increased risk for the prednisolone group.
Almayali confirmed there was no evidence of adrenal insufficiency among the 60 prednisolone-treated and 72-placebo-treated patients evaluated for this outcome.
“Taking all these findings together, they seem to suggest that withdrawal of low-dose prednisolone is feasible after 2 years of administration,” Almayali concluded.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group