Data from a controversial double-blinded RCT suggest weaning actually is possible.
A three-month tapering of long-term low-dose glucocorticoids in rheumatoid arthritis patients aged 65 and over was both feasible and safe, according to data from a follow-up study to the GLORIA trial.
The GLORIA trial was published in the Annals of the Rheumatic Diseases last year and was also highlighted as one of the year’s top papers in the ACR22 Clinical Year in Review.
It looked at the benefits and harms of 5mg/day prednisolone added to standard of care in RA patients aged 65 and over for two years. The treatment resulted in a DAS28 0.37 points lower than placebo (p<0.0001) and reduction in joint damage.
In terms of harms, more patients in the prednisolone group than the placebo group experienced adverse events, mostly mild to moderate infections requiring treatment.
The current study, also published in the Annals of the Rheumatic Diseases, implemented blinded linear tapering of study medication (prednisolone or placebo) over three months among the patients who had successfully completed the original study.
The primary outcome was three-month change in DAS28-ESR from the start of the tapering period, with flares and signs and symptoms of adrenal insufficiency the secondary outcomes.
At the end of the three months, the DAS28-ESR was 3.12 in the prednisolone group and 3.11 in the placebo group. This represented a moderate increase from baseline in the prednisolone group (from 2.88, p=0.04) but disease activity level was still considered low. Disease activity in the placebo group, which had a DAS28 of 3.08 at baseline, was stable over the three-month taper.
Around 45% of the prednisolone group experienced flares, compared with 33% of the placebo group. The difference was not statistically significant, although that may have been due to inadequate power.
“The risk of flares was numerically increased without any evidence of adrenal insufficiency, suggesting that withdrawal of low-dose prednisolone in a 3-month schedule is feasible and safe after long-term administration,” the authors wrote.
“Stopping GCs obviously decreases the chance of any GC-related adverse events, and our findings should alleviate fears that low-dose GCs cannot be stopped when given outside a bridging setting,” they concluded.
The GLORIA study was considered controversial as international guidelines recommend the use of glucocorticoids only as a bridging therapy in RA, and preferably not at all. When used, it’s advised they should be tapered and stopped as soon as possible. However, in conducting the pragmatic study, the researchers pointed out that despite this advice, chronic low-dose glucocorticoid treatment is widely prescribed in RA.
“The current study adds to the evidence of the GLORIA trial and other studies that suggest an acceptable balance of benefit and harm of low-dose GCs at least up to 2 years,” wrote the authors.
“It also addresses an important aspect for the (EULAR) research agenda on how to manage and taper patients on chronic low-dose GCs, and alleviates the fears voiced in the ACR guideline regarding ‘the frequent difficulty tapering GCs leading to undesirable prolonged use’.
“We propose that this guideline that advises against the use of GC, and the EULAR recommendation that advises rapid tapering as soon as possible, should be amended to allow for more personalised and shared decisions on the duration, dose and tapering of this important class of drugs.”
