A newly issued set of clinical recommendations offers surgeons guidance in preventing periprosthetic joint infection (PJI) through medication management in arthroplasty patients who have inflammatory rheumatic diseases.
Certain drugs may increase a patient's risk of infection. The guideline, developed collaboratively by the American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS), provides seven recommendations regarding when to continue, withhold, and restart medications commonly used to treat inflammatory rheumatic diseases, including rheumatoid arthritis (RA), spondyloarthritis (SpA), and systemic lupus erythematosus (SLE)."
"We felt there was an important need for perioperative management recommendations that could be subscribed to by both orthopaedic surgeons and rheumatologists in order to provide patients with inflammatory arthritis improved outcomes," said Bryan D. Springer, MD, of OrthoCarolina Hip and Knee Center, who served as coprincipal investigator for the guideline project. Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery, served as the other coprincipal investigator.
"While the widespread use of disease modifying antirheumatic drugs (DMARDs) and biologics have greatly assisted in the management of patients with inflammatory disease such as RA and lupus, they have not substantially decreased the utilization of total joint arthroplasty in this population," Dr. Springer said.
"About 75 to 80 percent of patients with inflammatory arthritis are on either a DMARD or biological medication at the time of joint replacement surgery. These medications, which alter the immune system, place patients at risk for development of PJI," he added.
In addressing medication management before and after elective hip and knee arthroplasty surgery, along with specifying optimal perioperative dosing of glucocorticoids, the guideline makes several key recommendations for reducing risk of infections, as follows:
- Discontinuing biologic therapy one dosing cycle prior to surgery in patients with inflammatory arthritis
- Withholding tofacitinib for at least 7 days prior to surgery in RA, SpA, and juvenile idiopathic arthritis patients
- Withholding rituximab and belimumab prior to surgery in all SLE patients undergoing arthroplasty
- Overall, Dr. Springer said, the guideline panel sought to answer the questions: Should antirheumatic medications be withheld prior to surgery? If so, when should they be stopped? And if they are withheld, when should they be restarted after surgery?
The guideline was presented in a special article published in the June issue of Arthritis Care & Research. The authors note that certain risk factors for infection, such as overall disability and disease or severity, are inherent in patients with RA and related diseases undergoing arthroplasty. Although those factors may not be modifiable, "the optimal perioperative management of immunosuppressant therapy around the time of arthroplasty may present an opportunity to mitigate risk."
The panel developing the guideline consisted of rheumatologists and orthopaedic surgeons specializing in hip and knee arthroplasty along with methodologists and infectious disease physicians. They conducted a multistep, systematic literature review and synthesized evidence for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period.
The recommendations in the guideline are issued as "conditional" and are based on low- or moderate-quality evidence. The authors also note that direct evidence in regard to perioperative management of antirheumatic drug therapy is "sparse," with no randomized controlled trials having been conducted to evaluate the cessation and reintroduction of biologic agents at the time of total hip or knee arthroplasty.
The 7 recommendations
In regard to the administration of DMARDs in the overall patient group covered by the guideline, the first recommendation is that use of these medications (methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine) be continued through surgery. The panel said the literature review indicated that the risk of infection was, in fact, decreased with continued use of DMARDs.
The second recommendation covers the use of biologic agents (including adalimumab, etanercept, golimumab, infliximab, rituximab, abatacept, and six others) and advises that all biologic agents be withheld in the overall patient group. These medications, Dr. Springer explained, should be stopped one dosing cycle prior to surgery, with surgery performed the following week at the end of the dosing cycle.
"For example," he said, "if the patient takes a biologic every 4 weeks, the patient would wait 4 weeks from the last dose, and surgery would be scheduled for the fifth week."
For the biologics recommendation, the guideline offers the following specific examples:
"Patients treated with adalimumab, routinely dosed at 2-week intervals, would plan their surgery in week 3, while patients treated with infliximab, when dosed every 8 weeks, would schedule their surgery in the week after the first withheld dose during week 9. Patients treated with rituximab every 6 months would schedule their surgery, when possible, at the week after the first withheld dose during month 7," according to the guideline.
Patients with SLE and receiving belimumab, which is given every 4 weeks, would schedule their surgery during week 5, the guideline advises.
The third recommendation addresses the use of tofacitinib in patients with RA, SpA (including ankylosing spondylitis [AS], and psoriatic arthritis [PsA]), and juvenile idiopathic arthritis (JIA). It advises withholding the drug at least 7 days prior to surgery. The guideline panel noted that because tofacitinib has "an extremely short serum half-life" the "recommendation for the duration of withholding may change in the future, as physician and patient experience with this drug grows."
In patients with severe SLE, the fourth recommendation counsels continuation of methotrexate, mycophenolic acid, azathioprine, cyclosporine, or tacrolimus. The panel noted that "there is a great deal of uncertainty and little published experience regarding risks in patients with severe SLE.
The panel wrote that along with its recommendation, "decisions regarding elective surgery in patients with severe SLE should be made on an individual basis with the patient's rheumatologist."
For patients with SLE that is not severe, the fifth recommendation advises withholding the current dose of mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus 1 week prior to surgery.
The sixth recommendation addresses the patients (RA, SpA [AS, PsA, JIA], and SLE) for whom biologic therapy was withheld prior to THA or TKA. It calls for resumption of biologics once the wound shows evidence of healing (typically around 14 days); all sutures/staples are out; there is no significant swelling, erythema, or drainage; and there is no clinical evidence of surgical site infection.
Finally, in adult patients with RA, SpA, or SLE who are receiving glucocorticoids for their rheumatic condition, the seventh recommendation suggests continuing the current daily dose "rather than administering perioperative supraphysiologic glucocorticoid doses (so-called 'stress dosing'). The panel noted that the recommendation does not apply to JIA patients who are receiving glucocorticoids (≤16 mg/day prednisone or equivalent), patients who may have been treated with glucocorticoids during childhood developmental stages, or patients receiving glucocorticoids to treat primary adrenal insufficiency or primary hypothalamic disease.
A product of consensus
In describing the collaborative process used to develop the guideline, Dr. Springer said, "We brought together major stakeholders with surgeons, rheumatologists, infectious disease doctors, epidemiologists, and methodologists."
He noted that the panel utilized the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, which "evaluates all available evidence and allows it to be scored based on quality."
By this method, he said, "Each recommendation went through a rigorous process by a guideline development and voting panel until consensus was reached based on available evidence. The guideline also allows for expert opinion to be utilized where evidence is lacking, which is why it was so important to have these major stakeholders involved."
Dr. Springer also noted that the guideline process included a patient panel that "took into consideration patient values and preferences."
"There was a very clear message from the patient panel that patients were willing to deal with flares if it meant reducing their likelihood for infections and other complications," said Dr. Goodman.
"The panel also noted that this preference could differ in lupus patients where a flare could mean inflammation of the organs, which poses a greater risk to their health than getting an infection from continuing their medications," he added.
The complete guideline is available at the ACR website (www.rheumatology.org) www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Perioperative.
Terry Stanton is the senior science writer for AAOS Now. He can be reached at firstname.lastname@example.org.