Low-Dose Glucocorticoids Lead to Modest Weight Gain in RA

In patients with rheumatoid arthritis (RA), a low dose of glucocorticoids given over 2 years slightly increased weight by approximately 1 kg more than controls, but did not increase blood pressure, according to a study published in Annals of Internal Medicine.¹

Andriko Palmowski, MD

Credit: The Parker Institute

Glucocorticoids, which effectively reduce disease activity and slow the progression of joint damage, are often used in the treatment and management of RA. However, these drugs are linked to a variety of adverse events, including weight gain and hypertension, particularly when given at higher dosages over a longer period of time.²

“Because patients with more severe disease, including higher disease activity, are more likely to be treated with glucocorticoids, and dose and duration are also strongly associated with disease severity, it is almost impossible to disentangle the effects of glucocorticoids and disease severity in an observational study,” wrote Andriko Palmowski, MD, Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Germany, and colleagues. “RCTs are protected from bias because allocation to treatment with or without glucocorticoids is by chance.”

A pooled analysis of 5 randomized controlled trials (RCTs) was conducted using research from 12 countries in Europe. Eligible RCTs examined patients with early and established RA receiving low-dose glucocorticoids (defined as ≤7.5 mg prednisone equivalent per day) for a 2-year period, and included a control group. Patients in the trials were allowed to receive concomitant disease-modifying antirheumatic drug (DMARD) treatment.

The primary endpoints were the change in body weight and mean arterial pressure from baseline. The difference in the change of number of antihypertensive drugs after 2 years of glucocorticoid treatment was also assessed. To determine the strength of the primary findings, investigators used subgroup and sensitivity analyses.

The 5 RCTs were comprised of 1112 participants (low-dose glucocorticoids, 548; controls, 564), with a mean age of 61.4 years and 68% were women. While there was heterogeneity across trials, weight and blood pressure levels were comparable at baseline. Most (n = 4) trials were blinded and controls were given placebo treatment.

Although patients in both the intervention cohort and control cohort gained weight, patients treated with glucocorticoids gained an average of 1.1 kg more (95% confidence interval [CI], .4 to 1.8 kg; P < .001) compared with controls. Mean arterial pressure increased by approximately 2 mm Hg in both groups, with a difference of .4 mm Hg (CI, 3.0 to 2.2 mm Hg) between cohorts. These results were confirmed in the subgroup and sensitivity analyses.

No differences were observed between groups regarding the number of antihypertensive drugs. The median change in the number of antihypertensives at the 2-year mark was 0 in both groups.

Investigators noted generalizability of the study may be limited, as all included trials originated in Europe. Additionally, as patients in RCTs are highly selected, they may not reflect the general population of patients with RA. The heterogeneity between trials, such as different dosages and applications, eligibility criteria, and the enrollment of patients in various countries, had the potential to hinder results. However, investigators believe this variety makes their results more robust. Lastly, although a 2-year intervention period is a relatively long time for RCTs, it does not allow for analysis of the long-term disease course of RA. The study was, however, strengthened by the large sample size, access to unpublished data, study execution protocol, and the expertise from a variety of study groups.

References

1. ^{Palmowski A, Nielsen SM, Boyadzhieva Z, et al. The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis: Individual Patient Data From Five Randomized Trials [published online ahead of print, 2023 Aug 15]. Ann Intern Med. 2023;10.7326/M23-0192. doi:10.7326/M23-0192}
2. ^{van der Goes MC, Jacobs JWG, Boers M, et al. Patient and rheu- matologist perspectives on glucocorticoids: an exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorti- coid therapy in rheumatic diseases. Ann Rheum Dis. 2010;69:1015-1021. [PMID: 19762359] doi:10.1136/ard.2009.114579}