Steroid Tapering Called Safe in Older RA Patients

Most rheumatoid arthritis (RA) patients 65 and older who had 5 mg/day of prednisolone added to standard care were successfully weaned from the steroid without seeing substantial increases in disease activity, researchers said.

In a follow-up to the randomized, placebo-controlled GLORIA trial, patients who had been assigned to the added prednisolone group had their doses tapered over 3 months after the main study concluded, while the placebo group continued as before. Mean 28-joint Disease Activity Score (DAS-28) values at the end of this period were just 0.16 points higher in the prednisolone group (P=0.12) after adjustment for baseline parameters, according to Abdullah Ali Hadi Almayali, MSc, of Amsterdam University Medical Center, and colleagues.

Although more patients in the steroid group experienced disease flares -- 45% versus 33% with placebo -- this difference, too, was not statistically significant in the 191-patient study (P=0.12), the researchers reported in Annals of the Rheumatic Diseases.

"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," Almayali and colleagues wrote. "Stopping GCs [glucocorticoids] 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."

GLORIA was a 2-year study to test whether adding a low-dose steroid to conventional disease-modifying antirheumatic drug (DMARD) therapy in 451 older RA patients would improve outcomes. The primary analysis showed that it did, with significantly lower levels of disease activity and radiographic progression. This benefit came, however, with a 24% higher rate of adverse effects.

The trial also included a prespecified follow-up analysis focusing on steroid withdrawal in the prednisolone group. This covered 278 of the original participants, after excluding 173 who left the trial early. Another 87 were not evaluable in the follow-up because of missing data or medication changes, leaving 191 for the final analysis: 96 in the prednisolone group and 95 on placebo.

Tapering was achieved by giving patients a schedule for each week, indicating which days they should take a capsule (5 mg prednisolone or placebo). In the first 2 weeks, one day each week (Saturday) was skipped. This gradually increased up to weeks 11-12, at which point patients were to take a capsule only on Sunday.

Mean patient age was about 72 and two-thirds were women. At the end of the primary GLORIA trial, mean DAS-28 values were 2.9 in the prednisolone group and 3.1 for those assigned to placebo. Following the 3-month tapering period, those previously on prednisolone saw a mean increase of 0.2 points (SD 1.0) while no mean change occurred in the placebo group (SD 0.8). (This analysis excluded an additional 36 patients who experienced flares and were treated with open-label steroids or DMARD changes.)

Other clinical evaluations, including the Health Assessment Questionnaire, physician's global assessment, and C-reactive protein levels, yielded similar results -- numerically higher in the prednisolone group but falling short of statistical significance.

Almayali and colleagues were also interested in adrenal insufficiency, a serious adverse effect often seen when steroids are stopped after long-term use. The researchers explained that such complications haven't been studied enough to know exactly what tapering schedule is best for avoiding them. Nine patients on prednisolone developed new symptoms of adrenal insufficiency during the tapering, but they abated in 14 who previously had them. Thus, the researchers concluded that their schedule was adequate.

Limitations included the many patients excluded for various reasons and missing data, leaving the study potentially underpowered. Also, the authors' definition of flare was not the current standard (GLORIA commenced in 2016). Perhaps most importantly, the study didn't include a control arm comprising patients continuing on low-dose prednisolone.

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