Meta-Analysis Examines Adverse Effects of Low-Dose Glucocorticoids for Rheumatoid Arthritis

Low-dose, long-term steroid therapy may not carry as much risk for weight gain or hypertension as previously thought for patients with rheumatoid arthritis (RA), according to a study published in Annals of Internal Medicine.¹

Glucocorticoids are one of the most common methods for managing RA. Their ability to slow progression of joint damage offers a myriad of benefits to patients with varying severities of RA; however, glucocorticoids have also been linked with certain adverse effects (AEs) for decades.² Of the AEs, patients with RA and rheumatologists list weight gain and hypertension as the most worrisome. This fear of AEs had even led official guidelines to advise against the use of low-dose, long-term glucocorticoids.

Previous observational studies demonstrate the connection between glucocorticoids and these AEs, but, as the researchers note, these results cannot fully account for the impact of glucocorticoids. Because individuals enduring more severe forms of RA are more commonly treated with glucocorticoids, the nature of these observational studies makes it difficult to “disentangle the effects of glucocorticoids and disease severity.”

To address this obstacle, the researchers conducted a meta-analysis of 5 randomized controlled trials (RCTs). As the issuing or abstaining from glucocorticoid treatment occurs by chance in RCTs, these studies are less prone to bias and paint a clearer picture discerning the consequences of long-term treatment.

Doctor examining patient with rheumatoid arthritis pain

To quantify the impact of glucocorticoids on weight loss and blood pressure, patient data were gathered from individuals who were administered daily low doses (7.5 mg or less of prednisone) over a 2-year period. Changes in body weight and mean arterial pressure (MAP) were measured from baseline until the 2-year mark. The researchers also tracked any changes in the number of administered antihypertensive drugs since many patients receive this medication throughout the course of glucocorticoid treatment.

Additional subgroup analyses were conducted that compared patients who were deemed overweight at baseline with those who were not, as well as patients with arterial hypertension at baseline and those without. Glucocorticoid doses were also assessed for any differentiating results between 7.5- vs 5-mg administration or their mode of application (orally or subcutaneously).

A total of 1112 randomized patients were included in the researchers’ analysis: 548 individuals receiving low-dose glucocorticoids and 564 individuals in the control group. They had a mean age of approximately 61 years, Disease Activity Score in 28 Joints of 4.87 (which indicates “moderate disease activity”), body weight of 73 kg, and MAP of 98 mm Hg.

After 2 years, both groups had gained weight. The individuals receiving glucocorticoids gained an average of 1.8 kg (and slightly less for groups taking 5-mg doses) whereas the controls gained an average of 0.7 kg (P < .0001). The only subgroup analyses that didn’t reveal any statistically significant differences in weight gain occurred between controls and those who received glucocorticoids subcutaneously.

As it pertains to blood pressure, each group registered an increase in MAP of more than 2 mm Hg; however, the differences in change were not statistically significant between the groups. The researchers noted that the same was true in their subgroup analyses. There also were no significant differences between those who received the 5- or 7-mg doses, nor oral or subcutaneous glucocorticoids.

The individuals categorized as overweight or who had hypertension at baseline did not reach statistically significant thresholds over the course of the researchers’ analysis.

Several limitations were named in this study, among which were the highly selective nature of populations included in RCTs, that the analyzed trials took place in Europe (which could affect generalizability), heterogeneity existed among patients across all studies, and systematic searches for literature were not utilized.

Overall, the researchers’ findings indicate that long-term, low-dose glucocorticoid use does not affect blood pressure over a 2-year period. Furthermore, it appears that weight gain associated with these therapies is limited. These results demonstrate how the AEs of low-dose glucocorticoid usage are not as burdensome and are far more manageable than past observational studies’ data indicate.

References

1. Palmowski A, Nielsen SM, Boyadzhieva A, 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. Ann Intern Med. Published online August 15, 2023. doi:10.7326/M23-0192

2. Fernández D. The pendulum swings on glucocorticoids in rheumatoid arthritis. Ann Intern Med. Published online August 15, 2023. doi:10.7326/M23-1991