What is the optimal timing to initiate immunosuppressant therapy following total knee arthroplasty (TKA) (knee replacement)?

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Last updated: March 3, 2025View editorial policy

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From the Guidelines

Immunosuppressant medications should typically be restarted 2-14 days after knee replacement surgery, with the exact timing depending on the specific medication and individual patient factors. For most traditional disease-modifying antirheumatic drugs (DMARDs) like methotrexate, leflunomide, and hydroxychloroquine, resumption can occur relatively early, around 2-3 days post-surgery when wound healing has begun 1. Biologic agents such as TNF inhibitors (adalimumab, etanercept) should be restarted later, approximately 10-14 days after surgery when the wound has demonstrated good healing and there are no signs of infection, as recommended by the 2017 American College of Rheumatology guideline 1. For JAK inhibitors like tofacitinib, a similar 10-14 day waiting period is recommended 1.

Key Considerations

  • The decision to restart antirheumatic therapy should be based on careful assessment of the patient’s wound status and clinical judgment for absence of surgical and non–surgical site infections 1.
  • Normal wound closure typically requires ~14 days, and biologic therapy can be restarted once the wound shows evidence of healing, all sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no clinical evidence of non–surgical site infections 1.
  • Patients should be monitored for signs of infection (redness, warmth, drainage, fever) or delayed wound healing after restarting these medications, and the orthopedic surgeon should be consulted before resuming any immunosuppressive therapy.

Medication-Specific Guidance

  • Traditional DMARDs: restart 2-3 days post-surgery 1
  • Biologic agents (e.g. TNF inhibitors): restart 10-14 days post-surgery 1
  • JAK inhibitors (e.g. tofacitinib): restart 10-14 days post-surgery 1

General Principles

  • Balance the risk of surgical site infections and wound complications against the risk of disease flares from prolonged medication discontinuation.
  • Consider the individual patient's factors, such as the specific medication, disease activity, and overall health status, when determining the optimal timing for restarting immunosuppressant therapy.

From the Research

Optimal Timing for Immunosuppressant Therapy

The optimal timing to initiate immunosuppressant therapy following total knee arthroplasty (TKA) is a topic of ongoing debate.

  • Studies have shown that delayed initiation of anti-TNF therapy in patients with severe rheumatoid arthritis (RA) is associated with an increased risk of total knee replacement (TKR) surgery 2.
  • The International Consensus Meeting on periprosthetic joint infection (PJI) recommends halting disease-modifying antirheumatic drugs (DMARDs) prior to elective total joint arthroplasty based on their half-life 3.
  • Recent guidelines from the American College of Rheumatology/American Association of Hip and Knee Surgeons recommend continuing conventional disease-modifying drugs and holding biologics for one dosing interval before surgery 4.

Perioperative Management of Immunosuppression

Perioperative management of immunosuppression in patients with rheumatoid arthritis is crucial to minimize the risk of infection.

  • Patients with rheumatoid arthritis are at increased risk of infection after surgery, and those treated with biologics are at greater risk of postoperative infection 4.
  • Glucocorticoids have consistently been found to be risk factors for infection, and should be minimized before surgery 4.
  • Prolonged interruption of conventional and biologic therapies before surgery does not appear to substantially reduce infection risk 4.

Risk Factors for Post-Operative Joint Infection

Several risk factors for post-operative joint infection have been identified, including:

  • Male gender 5
  • Diagnosis of rheumatoid arthritis 5
  • Diabetes mellitus 5
  • Obesity 5
  • Gout 5
  • Prescription for prednisone 5 These risk factors can help identify high-risk patients and inform clinical decision-making regarding immunosuppressant therapy and perioperative management.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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