New drugs, new guidelines: ACR/AAHKS update treatment recommendations in joint replacement
Joint replacement in patients with inflammatory arthritis is often beset with pitfalls like disease flares and infectious complications, and up until recently, the emergence new treatments were rendering the current guidelines outdated.
That all changed in February, when the American College of Rheumatology and the American Association of Hip and Knee Surgeons (AAHKS) updated their “Guideline for the Perioperative Management of Antirheumatic Medication in Patients with Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.” It was the first update of these guidelines since 2017.
“Since the guidelines were first introduced in 2017, several new medications have been introduced to the market,” Bryan D. Springer, MD, of OrthoCarolina Hip and Knee Center, and fellowship director and professor of orthopedic surgery at Atrium Musculoskeletal Institute, in Charlotte, North Carolina, told Healio. “In addition, since it has been 5 years since the prior publication, we thought it would be important to add any new studies that have been published on the medications that were available in the 2017 guidelines.”
The guideline update issues new recommendations for patients with systemic lupus erythematosus, spondyloarthritis, juvenile idiopathic arthritis, rheumatoid arthritis and other forms of inflammatory arthritis.
It also considers for the first time the emergence of novel medications such as apremilast (Otezla, Amgen), anifrolumab (Saphnelo, AstraZeneca), voclosporin (Lupkynis, Aurinia), ixekizumab (Taltz, Eli Lilly & Co.) and guselkumab (Tremfya, Janssen), according to Susan M. Goodman, MD, professor of clinical medicine at Weill Cornell Medicine and attending rheumatologist at the Hospital for Special Surgery.
“In addition, expanded indications for belimumab (Benlysta, GlaxoSmithKline) for lupus nephritis and wider acceptance of rituximab (Rituxan, Genentech) in lupus has changed our recommendations to include them in the roster for severe SLE,” she said.
Springer acknowledged that many of these new medications do not have “robust” data pertaining to perioperative management of hip and knee arthroplasty.
“However, we felt it important to at least offer expert guidance on how to manage these new medications, as well as update the 2017 guidelines with any additional literature that may affect interpretation of the prior guidelines,” he said. “It is important that as new studies, new information and new drugs become available, the existing guidelines are periodically updated.”
The guideline development team included rheumatologists, orthopedic surgeons and infectious disease specialists, along with a patient panel. After conducting a systematic literature review, a set of clinically relevant population, intervention, comparator and outcomes (PICO) questions were developed.
At this point, the group used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations.
Ultimately, the group arrived at seven recommendations, all of which are conditional and based on low- or moderate-quality evidence, according to the authors.
Springer acknowledged that “true level one” evidence was limited for most of the medications covered in the document. That said, the guideline team made the most of what was available.
The first recommendation is to continue the current dose of methotrexate, leflunomide, hydroxychloroquine, and/or sulfasalazine for patients undergoing elective total hip or knee arthroplasty, while the second is to withhold all current biologic agents before surgery. The procedure should be planned for the end of the dosing cycle for that specific medication.
The third recommendation is that tofacitinib (Xeljanz, Pfizer) should be held for at least 7 days prior to surgery in patients with RA, SpA — including AS and PsA — or JIA. The fourth urges providers to continue the current dose of methotrexate, mycophenolate mofetil, azathioprine, cyclosporine or tacrolimus through the surgical period in all patients, while the fifth recommends withholding the current dose of mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus 1 week before surgery in all patients.
For the sixth recommendation, it is suggested that, in patients who withheld biologics, these drugs should be restarted once the surgical wound shows evidence of healing, which is typically around 14 days, according to the authors. Restarting may occur when “all sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no clinical evidence of non-surgical site infections,” they wrote.
“We continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery and scheduling the surgery after that dose would be due,” Springer said.
Lastly, the seventh recommendation covers patients receiving glucocorticoids for RA, SpA, or SLE, and suggests that the current dose, rather than an elevated dose, should be administered in the arthroplasty perioperative setting.
“As patients with inflammatory arthritis and SLE are at increased risk for infection after total hip and total knee arthroplasty, we aimed to balance the risk of perioperative infection and the risk of disease flares,” Springer said.
The risk-benefit equation is largely dependent on how drugs are deployed in the arthroplasty setting. Understanding new approvals and new indications is critical to balancing that equation.
‘Any risk for infection is more worrisome than a flare’
“There was no one specific medication that triggered these guidelines,” Springer said. “When our first guidelines were released in 2017, we understood that these would need to periodically be updated based on new medications and new evidence on older medication.”
That said, Goodman provided a rundown of some drug-specific considerations in the updated guidelines that account for approvals since 2017.
“Apremilast has minimal immunosuppression, so the risk of continuing is minimal,” she said. “We do not recommend stopping it.”
Regarding the use of anifrolumab and voclosporin in severe SLE, Goodman noted that a flare risks the threat of organ damage.
“Severe SLE risks cannot be generalized but should be reviewed with the patient’s rheumatologist,” she said.
Another key change to the guideline covers the treatment of inflammatory arthritis with ixekizumab or guselkumab.
“Patients have told us that any risk for infection is more worrisome than a flare of arthritis, so we respect that and recommend withholding the medication,” Goodman said.
Regarding specific clinical scenarios, Springer gave an example of a patient who takes a medication every 4 weeks.
“In that case, the patient would withhold the dose of the medication and schedule surgery in the fifth week,” he said.
The new guidelines also shorten the recommended time between the last dose of a janus kinase (JAK) inhibitor and surgery from 7 days to 3 days, according to Goodman.
“This recommendation was based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressing effect wears off sooner than we previously thought,” she said.
Another key to optimizing outcomes relates to specific arthritides and other conditions covered in the guideline.
According to Goodman, the heterogeneity of RA, JIA and SpA impacted the way the guideline development team approached these diseases.
“These are different types of inflammatory arthritis, so the flares, while significant, would not be organ-threatening as they may be for patients with SLE,” she said. “We do worry that a severe flare might make post-op mobilization more challenging, but it is typically manageable.”
Another new recommendation, pertaining to SLE, suggests providers now continue biologics — such as rituximab and belimumab — in patients with severe disease. However, these drugs should be withheld in less severe cases where there is little risk of organ damage, Goodman said.
With so many conditions and drugs to consider, it was both natural and necessary for the guideline development to be a joint effort between the ACR and AAHKS.
Societies, specialties ‘on the same page’
According to Goodman, the ACR and AAHKS aimed to benefit physicians and patients who are dealing with inflammatory arthritis and facing total joint replacement.
“The ACR is the foremost organization for the rheumatological diseases while AAHKS is the leading organization for total hip and knee arthroplasty,” she said.
Springer added that the two societies undertook the joint effort partly because patients with these diseases are likely to use many of the medications that are included in the document.
“Another reason is that, often times, these patients require total hip or knee arthroplasty,” he said. “An expert panel from both organizations was needed to ensure comprehensive management.”
For Springer, a diverse guideline development team was necessary to reflect and account for the heterogeneity of potential patient scenarios.
“It is most important to remember that this is a team approach with orthopedic surgeons, rheumatologist and our patients with inflammatory arthritis,” he said. “Patients with inflammatory arthritis can be very complex. Communication is the key to management.”
With that in mind, an important benefit of the guideline is that it puts all of those players “on the same page” regarding the risks and benefits of continuing, and withholding, these medications in the perioperative period, Springer said.
“These recommendations provide general guidelines for medication management,” he said. “Each patient should be considered individually and in a shared decision-making model with their physician.”
For Goodman, the use of these guidelines in clinical practice is key. Such a document would be irrelevant, and all the time and effort poured into it would be for nothing, if it is not implemented into daily clinical practice, she said.
“It is important to spread the word to ensure maximum utilization for the benefit of patients,” she said. “Our expectation is that these guidelines will be taken up widely, and the best way to achieve that is to include stakeholders such as orthopedic hip and knee surgeons as well as patients in the project.”
Goodman SM, et al. Arth Care & Res. 2022;doi:10.1002/acr.23274.