Stopping bDMARDs Before RA Hip, Knee Arthroplasty Questioned

Janis C. Kelly

May 22, 2019

Stopping biologic disease-modifying antirheumatic drugs (bDMARDs) for patients with rheumatoid arthritis (RA) before they undergo hip or knee replacement might increase postoperative infection risk if it leads to increased use of glucocorticoids (GCs) to control disease flares, a study suggests.

Guidelines advise stopping bDMARDs before patients with RA undergo hip or knee replacement, but the investigators say more research is needed to determine whether stopping bDMARDs actually improves outcomes.

The authors write, "[P]atients with RA who are treated with various bDMARDs before total hip or knee arthroplasty have similar rates of postoperative infection and readmission. Glucocorticoid use is strongly associated with postoperative infection risk even at modest doses. Minimizing glucocorticoid exposure before surgery should be a primary focus of perioperative medication management."

The study, by Michael D. George, MD, University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues, was published online May 20 in the Annals of Internal Medicine.

The use of even modest doses of GC before surgery (5 – 10 mg/day), in comparison with no GC use, was associated with a 30% higher postoperative risk that RA patients would be hospitalized for infection within 30 days after joint replacement or for prosthetic joint infection (PJI) within 1 year after surgery. GC doses >10mg/day doubled the postoperative risk. There were no major differences in postoperative risk associated with use of various biologic therapies.

In a linked editorial, Bheeshma Ravi, MD, PhD, and Gillian Hawker, MD, from the University of Toronto, Ontario, Canada, note that the analysis could not determine whether biologic therapy per se increased risk, because the study did not include a group of patients who received nonbiologic therapy and because the authors could not differentiate patients for whom biologics had been withheld before surgery from those who continued taking biologics.

"An obvious concern about withholding biologic therapies in the perioperative period is that this may result in RA flare, necessitating an increase in glucocorticoid dosage. Given the strong relationship between glucocorticoid therapy and risk for postoperative infection found in this study and others, additional research is warranted to determine the management approach that is associated with lowest risk for serious postoperative infection," Ravi and Hawker write.

George and colleagues used data from the Medicare and Truven MarketScan administrative databases to compare postoperative infection risks in nearly 10,000 patients with RA following primary or revision total knee or hip arthroplasty.

Patients had been treated with abatacept (Orencia, Bristol-Myers Squibb), adalimumab (multiple brands), etanercept (multiple brands), infliximab (multiple brands), rituximab (multiple brands), or tocilizumab (Actemra, Genentech) before surgery. In addition to the bDMARD, 43.0% of patients had received GCs, and 45.6% had received methotrexate within 90 days before surgery. The median age of the patients was 65.1 years, 83.0% of the patients were women, and 89.5% of the procedures were primary. Only 3.9% of patients had received GC doses >10 mg/day (median, 12.1 mg/day).

The primary outcomes were infection requiring hospitalization within 30 days after surgery and PJI within 1 year after surgery. The researchers evaluated comparative risks associated with biologics and with different doses of GCs.

Ravi and Hawker comment that most of these arthroplasties were performed in "low-volume" hospitals. In only 5.8% of the hospitals in the Medicare database were more than 10 of the procedures performed per year.

The researchers say that too few patients were treated with rituximab or tocilizumab to allow accurate risk estimates but that for the other four biologics, the predicted risk for hospitalized infections ranged from 8.16% to 9.57%. The predicted 1-year cumulative incidence of PJI ranged from 2.12% to 2.81%. With GCs, the predicted risk was dose dependent. For Medicare patients, the predicted risk for infection that required hospitalization was 8.10% without GCs, 9.44% for GCs at doses ≤5 mg/day, 10.14% for GCs at doses >5 – 10 mg/day, and 17.23% for doses >10 mg/day. Predicted 1-year cumulative PJI incidence was 2.63% for doses ≤5 mg/day, 2.70% for doses >5 – 10 mg/day, and 4.82% for doses >10 mg/day.

"In this study of patients with RA having elective hip or knee arthroplasty, we found that rates of serious postoperative infection and 30-day readmission were similar between biologics. Glucocorticoids, however, were associated with a dose-dependent increase in the risk for postoperative outcomes, with greater risk even with modest doses of glucocorticoids, suggesting that limiting glucocorticoids should be a focus of perioperative management," the researchers explain.

They note that although recent guidelines recommend avoiding doses higher than 20 mg/day, this study suggests that postoperative risk is increased even at doses of 5 – 10 mg/day.

Use of methotrexate was not associated with increased postoperative risk.

Ravi and Hawker stress that this study does not resolve the question of whether withholding biologic therapies in the perioperative period reduces patients' overall risk for infection complications. They write, "Instead, it provides compelling evidence, once again, of the substantial risk for serious postoperative infections associated with glucocorticoid use. There is a critical need for research to elucidate the risks and benefits of withholding biologics to optimize patient outcomes."

The study was supported by Bristol-Myers Squibb. George reports receiving personal fees from Bristol-Myers Squibb and AbbVie outside the submitted work. Coauthors' relevant financial relationships are listed in the original article. Editorialists Ravi and Hawker have disclosed no relevant financial relationships.

Ann Intern Med. published online May 21, 2019. Full text, Editorial

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