Administration of infliximab within 4 weeks of elective knee or hip arthroplasty did not have any significant effect on patients’ risk of serious infection after surgery, whereas the use of glucocorticoids increased that risk, in an analysis of a Medicare claims database.
“This increased risk with glucocorticoids has been suggested by previous studies [and] although this risk may be related in part to increased disease severity among glucocorticoid treated patients, a direct medication effect is likely. [These data suggest] that prolonged interruptions in infliximab therapy prior to surgery may be counterproductive if higher dose glucocorticoid therapy is used in substitution,” wrote the authors of the new study, led by, of the University of Pennsylvania in Philadelphia.
Dr. George and his colleagues examined data from the U.S. Medicare claims system on 4,288 elective knee or hip arthroplasties in individuals with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months prior to the operation during 2007-2013 ().
The patients had to have received infliximab at least three times within a year of their procedure to establish that they were receiving stable therapy over a long-term period. The investigators also looked at oral prednisone, prednisolone, and methylprednisolone prescriptions and used data on average dosing to determine how much was administered to each subject.
“Although previous studies have treated TNF stopping vs. not stopping as a dichotomous exposure based on an arbitrary (and variable) stopping definition, in this study the primary analysis evaluated stop timing as a more general categorical exposure using 4-week intervals (half the standard rheumatoid arthritis dosing interval) to allow better assessment of the optimal stop timing,” the authors explained.
Stopping infliximab within 4 weeks of the operation did not significantly influence the rate of serious infection within 30 days (adjusted odds ratio, 0.90; 95% CI, 0.60-1.34) and neither did stopping within 4-8 weeks (OR, 0.95; 95% CI, 0.62-1.36) when compared against stopping 8-12 weeks before surgery. Of the 4,288 arthroplasties, 270 serious infections (6.3%) occurred within 30 days of the operation.
There also was no significant difference between stopping within 4 weeks and 8-12 weeks in the rate of prosthetic joint infection within 1 year of the operation (hazard ratio, 0.98; 95% CI, 0.52-1.87). Overall, prosthetic joint infection occurred 2.9 times per 100 person-years.
However, glucocorticoid doses of more than 10 mg per day were risky. The odds for a serious infection within 30 days after surgery more than doubled with that level of use (OR, 2.11; 95% CI, 1.30-3.40), while the risk for a prosthetic joint infection within 1 year of the surgery also rose significantly (HR, 2.70; 95% CI, 1.30-5.60).
In an interview,, a rheumatologist at the Hospital for Special Surgery in New York, lauded the study and spoke about the importance of its findings.
“This is a very well done paper that adds important observational data to our understanding of perioperative medication risk,” Dr. Goodman said.
But the study results will not, at least initially, bring about any changes to the proposed guidelines for perioperative management of patients taking antirheumatic drugs that were described at the 2016 annual meeting of the American College of Rheumatology, she said.
“We were aware of the abstract, which was also presented at the ACR last fall at the time the current perioperative medication management guidelines were presented, and it won’t change guidelines at this point,” said Dr. Goodman, who is one of the lead authors of the proposed guidelines. “[But] I think [the study] could provide important background information to use in a randomized clinical trial to compare infection on [and] not on TNF inhibitors.”
The proposed guidelines conditionally recommend that all biologics should be withheld prior to surgery in patients with inflammatory arthritis, that surgery should be planned for the end of the dosing cycle, and that current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with rheumatoid arthritis, lupus, or inflammatory arthritis.
The National Institutes of Health, the Rheumatology Research Foundation, and the Department of Veterans Affairs funded the study. Dr. George did not report any relevant financial disclosures. Two coauthors disclosed receiving research grants or consulting fees from pharmaceutical companies for unrelated work.
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