Add-on low-dose prednisolone improves long-term disease activity and progression in senior patients with established rheumatoid arthritis, albeit with an increase in non-severe adverse events, according to data.
“Most experts agree that long-term [glucocorticoid (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,” Maarten Boers, MD, PhD, of Amsterdam University Medical Centers and co-authors, wrote in Annals of the Rheumatic Diseases. The limited data from trials (mostly in early RA) do not support strong claims of harm, but their generalizability is questioned. Pragmatic trials to overcome this have not been attempted. This lack of information results in a wide range of usage patterns, but overall, a high prevalence of chronic use.
“RA prevalence increases with age, peaking at age 70, so we can expect more RA in ageing populations,” they added. “Seniors have the highest risk for treatment–associated harm, given comorbidity and its treatment. Regrettably, seniors are under-represented or even excluded from clinical trials that provide the evidence base for treatment of RA.”
To investigate the benefit and harm balance of initiating low-dose glucocorticoid therapy in patients with RA, Boers and colleagues conducted GLORIA (Glucocorticoid Low-dose in Rheumatoid Arthritis), a the 2-year randomized, double-blind, placebo-controlled trial. The study was conducted at 28 centers across seven European Union nations, and enrolled participants aged 65 years or older with RA at “more than minimal disease activity,” the researchers wrote. For the study, this was defined as a DAS28 score greater than or equal to 2.6.
Patients were randomized 1:1 to receive daily prednisolone 5 mg or a placebo for 2 years. Throughout the trial period, patients received standard of care antirheumatic treatment. Included in the guidance was a recommendation for all patients to receive calcium 500 mg and vitamin D3 800 IU supplementation. Additionally, all cotreatments, except for chronic oral glucocorticoids, were allowed.
Medication adherence was measured by counting returned capsules, and investigators considered patients to have “good adherence” if they took more than 80% of the capsules. Outcomes requiring physical examination of the patient were conducted at baseline and 3, 6, 12, 18 and 24 months. The primary outcome for patient benefit was DAS28.
For harm, the co-primary endpoints included the total number of patients who had at least one adverse event of special interest. These included any serious adverse events, any event leading to discontinuation, myocardial infarction, cerebrovascular or peripheral arterial vascular event, newly occurring hypertension, diabetes, infection, cataract or glaucoma requiring treatment and symptomatic bone fractures.
In all, the study included 451 randomized patients with established RA. On average, patients were aged 72 years and had 2.1 comorbidities, with a disease duration of 11 years. Patients receiving prednisolone had 0.37 points lower disease activity (P < .0001) and joint damage was lower by 1.7 points (P = .003).
Overall, 60% of patients receiving prednisolone, compared with 49% of those in the placebo group, experienced a harm outcome (adjusted RR = 1.24; 95% CL, 1.24).
“In patients with RA aged 65+ on standard care that allowed treatment optimization, add-on low-dose prednisolone had beneficial long-term effects on disease activity and damage progression,” Boers and colleagues wrote. “The trade-off was an 11% increase in the number of patients with at least one [adverse event of special interest (AESI)]. Among events traditionally associated with GC, the increase comprised mostly mild to moderate infections requiring treatment.
“Although of concern, these should be interpreted in the light of the high-risk trial population, resembling patients in clinical practice,” they added. “We suggest that our results constitute a benchmark for the upper limit of harm to be expected with this dose and duration. However, this assumes care by rheumatologists as given in this trial.”