Safe Withdrawal of Low-Dose Prednisolone After 2 Years in RA

Recent study results published in Annals of Rheumatic Disease suggest it is possible to safely withdraw low-dose prednisolone after a 2-year period of administration among patients with rheumatoid arthritis (RA).

Investigators assessed the effects of withdrawing low-dose glucocorticoids following long-term administration among patients with RA.

An observational controlled cohort study was conducted, following-up the multicenter, double-blind Glucocorticoid Low-dose in Rheumatoid Arthritis (GLORIA; ClinicalTrials.gov Identifier: NCT02585258) trial for 3 months.

In the present study, patients who completed the 2-year trial period gradually reduced and discontinued the use of the blinded study medication (prednisolone 5 mg/day or placebo) within a 3-month time frame. The investigators reported on the change in Disease Activity Score 28-Erythrocyte Sedimentation Rate ESR (DAS28-ESR) over a 3-month period, from the final trial visit.

Secondary outcomes included occurrence of disease flares and changes in the number of signs and symptoms related to adrenal insufficiency.

A total of 191 patients (prednisolone, n= 96; placebo, n=95) were included in the analysis.  At the final trial visit, the mean patient age was 72 years and mean DAS28 score was 3.0. Additionally, 69% of the participants were women.

Between week 5 and week 12, 33 patients received open-label glucocorticoids. Additionally, 4 patients received an increase in their disease-modifying antirheumatic drug (DMARD) dose or switched DMARDs, which was classified as a flare. These patients were excluded from the primary outcome analysis of DAS28 scores and the analysis of adrenal insufficiency.

Out of the total participants, 36 patients met the criteria for treatment-related flare and were only included in the flare analysis. The mean change in DAS28 scores at follow-up was 0.2 (standard deviation [SD], 1.0) among the prednisolone group (n=76) and 0.0 (SD, 1.2) among the placebo group (n=79).

After adjusting for values at the end of the GLORIA trial, the difference in the increase of DAS28 scores between both groups was 0.16 (95% confidence limit, -0.06; P =.12).

Flares were observed among 45% of patients in the prednisolone group compared with 33% in the placebo group, with a relative risk of 1.37 (95% CI, 0.95-1.98; P =.12).

Age (P =0.23) and sex (P =0.94) did not show effect modification.

There was no evidence of adrenal insufficiency according to signs and symptoms or adrenocorticotropic hormone/cortisol spot measurements.

The study authors concluded, “Together with the evidence of an acceptable balance of

benefit and harm demonstrated in the GLORIA trial, current treatment guidelines for RA should be updated to allow more personalised and shared decisions on the duration, dose and tapering of this important class of drugs.”

Disclosure: This research was supported by the European Union’s Horizon 2020 research and innovation program under grant agreement number 634886. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.