Low-dose glucocorticoids for rheumatoid arthritis lead to small weight gain

Key takeaways:

• Low-dose glucocorticoids did not significantly affect BP.
• However, they were linked to an average of 1.1 kg increase in weight vs. a control group.

When taken over 2 years for rheumatoid arthritis, low-dose glucocorticoids were associated with slight weight gain, but they did not significantly affect BP, according to research published in Annals of Internal Medicine.

Hypertension and weight gain are widely recognized adverse events of high-dose glucocorticoids treatment, Andriko Palmowski, MD, a physician and researcher with Charité — Universitätsmedizin Berlin, and colleagues wrote. Observational studies have repeatedly shown associations between the use of glucocorticoids for rheumatoid arthritis and hypertension and weight gain, but those studies are vulnerable “to various sorts of confounding,” according to the researchers.

“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,” they wrote.

Randomized controlled trials are not at risk for this bias because being treated with or without the medication “is by chance,” the researchers wrote. But they can also have small sample sizes, reducing the trial’s statistical power. So, the researchers combined data from 1,112 participants with RA who were enrolled in five randomized controlled trials to assess the effects of treatment with glucocorticoids at 7.5 mg or less prednisone equivalent per day over 2 years. Among the cohort, 548 were assigned to glucocorticoids and the remaining were assigned to a control group.

Palmowski and colleagues found “robust evidence” indicating that 2 years of low-dose glucocorticoid treatment for RA did not affect BP but increased weight by about 1 kg.

In both groups, mean arterial pressure rose by roughly 2 mm Hg, with a between-group difference of 0.4 mm Hg (95% CI, 3-2.2).

Both groups of participants also gained weight, but those who received glucocorticoids gained on average an additional 1.1 kg (95% CI, 0.4-1.8) more compared with those in the control group.

These results, the researchers wrote, were consistent in subgroup and sensitivity analyses.

“Our subgroup analyses indicate that a 2-year treatment with glucocorticoids, even at a low dose of 5 mg per day, leads to some weight gain in patients with RA. However, only about 1 additional kilogram is gained on average with 5 mg per day, and only slightly more with 7.5 mg per day,” Palmowski and colleagues wrote. “In the clinic setting with individual patients it is important to stress that about only half of the reported weight gain in the trial population is due to glucocorticoids.”

David Fernandez, MD, PhD, a rheumatologist at Hospital for Special Surgery in New York, wrote in a related editorial that the results “are very helpful in defining in more concrete terms the precise effect of glucocorticoids in rheumatoid arthritis, but they have some limitations.” For example, the limited time scale to evaluate the effect of hypertension and weight gain and the fact that the study cannot evaluate “the full panoply of glucocorticoid adverse effects.”

“These findings provide a more quantifiable assessment of the potential adverse effects of steroid therapy than had existed previously and will be helpful to providers and patients as they decide on the relative risks and benefits of glucocorticoids as part of their therapy plan in rheumatoid arthritis,” Fernandez wrote.

References:

• Fernandez D, et al. Ann Intern Med. 2023;doi:10.7326/M23-1991.
• Palmowski A, et al. Ann Intern Med. 2023;doi:10.7326/M23-0192.