Study Highlights Importance of Limiting Glucocorticoid Use in Biologic-Treated Patients With RA

Patients with rheumatoid arthritis (RA) have similar rates of infection after total knee or hip replacement no matter which biologic they take, but those using glucocorticoids, even moderate doses, appear to have an increased risk of postoperative infections, according to a study published today.

The researchers said their findings suggest that limiting use of glucocorticoids should get more attention in this population of patients undergoing surgery.

Biologics are linked to increased risk for infection, although studies in surgical patients are lacking, the researchers said. However, patients with RA frequently have orthopedic surgery.

The retrospective cohort study, published in Annals of Internal Medicine, checked to see if any variability existed by biologic—abatacept, adalimumab, etanercept, infliximab, rituximab, and tocilizumab.¹

Using Medicare claims as well as claims from the Truven Marketscan database from January 2006 through September 2015, researchers compared risk for infections after surgery and readmissions in patients with RA on these therapies.

They also evaluated the risk of postoperative infection in patients using glucocorticoids. evaluated comparative risks for hospitalized infection within 30 days and prosthetic joint infection (PJI) within 1 year after surgery between biologics or with different dosages of glucocorticoids. Secondary analyses evaluated non—urinary tract hospitalized infections, such as pneumonia, and 30-day readmissions.

Among 9911 patients, 10,923 were treated with biologics, and outcomes were similar across different types of therapies.

Compared with an 8.16% risk for hospitalized infection with abatacept, predicted risk ranged from 6.87% (95% CI, 5.30%-8.90%) with adalimumab to 8.90% (95% CI, 5.70%-13.52%) with rituximab.

Compared with a 2.14% 1-year cumulative incidence of PJI with abatacept, predicted incidence ranged from 0.35% (95% CI, 0.11%-1.12%) with rituximab to 3.67% (95% CI, 1.69%-7.88%) with tocilizumab.

Glucocorticoids were associated with a dose-dependent increase in postoperative risk for all outcomes; use of more than 10 mg of glucocorticoids per day (versus no glucocorticoid use) resulted in a predicted risk for hospitalized infection of 13.25% (95% CI, 9.72%-17.81%) versus 6.78%, and a predicted 1-year cumulative incidence of PJI of 3.83% (95% CI, 2.13%-6.87%) versus 2.09%.

An accompanying editorial noted that a 2017 guideline from the American College of Rheumatology and the American Association of Hip and Knee Surgeons recommends that patients with RA having arthroscopic surgery avoid biologic agents before surgery to reduce the risk of infection. ²

However, withholding biologics could raise the risk of an RA flare before surgery, which would then require an increase in glucocorticoid dosage. Given the relationship between glucocorticoid dosage and infection risk postsurgery, additional research is needed to determine how to best manage these patients, the editorial said.

The editorial’s authors called the finding about glucocorticoids “compelling.”

The study had some limitations. Residual confounding is possible, although the researchers only evaluated patients receiving biologics because those not receiving such therapy are different. In addition, sample sizes for patients treated with rituximab and tocilizumab were small.

The study was funded by the Rheumatology Research Foundation, the National Institutes of Health, and Bristol-Myers Squibb.

References

1. George MD, Baker JF, Winthrop K, et al. Risk of biologics and glucocorticoids in patients with rheumatoid arthritis undergoing arthroplasty [published online May 21, 2019]. Ann Intern Med. doi:10.7326/M18-2217.

2.Ravi B, Hawker G. Elucidating the risks and benefits of withholding biologics to optimize surgical outcomes [published online May 21, 2019]. Ann Intern Med. doi:10.7326/M19-1088.