Should methotrexate be discontinued prior to total knee arthroplasty (TKA) surgery?

From the Guidelines

Methotrexate should generally be continued during the perioperative period for total knee replacement surgery. Patients taking methotrexate for rheumatoid arthritis or other inflammatory conditions should maintain their regular dosing schedule before, during, and after surgery, as recommended by the 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty 1. This recommendation is based on low to moderate evidence that suggests continuing methotrexate does not increase infection risk and may provide benefits by maintaining control of the underlying inflammatory condition.

Some key points to consider:

• The recommendation to continue methotrexate applies to standard doses used for autoimmune conditions (typically 7.5-25 mg weekly) 1.
• Higher doses used for cancer treatment would require different considerations, and patients should discuss their specific situation with both their rheumatologist and orthopedic surgeon 1.
• Individual factors such as kidney function, other medications, and overall health status might occasionally warrant temporary adjustment of the medication regimen 1.
• Stopping methotrexate can lead to disease flares that might complicate recovery and rehabilitation after knee replacement, and current evidence indicates that continuing methotrexate does not increase infection risk 1.
• The 2022 guideline recommends continuing the usual dosing of methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, and/or apremilast through surgery for patients with RA, AS, PsA, JIA, or all SLE undergoing THA or TKA 1.

Overall, the current evidence supports continuing methotrexate during the perioperative period for total knee replacement surgery, and patients should discuss their specific situation with their healthcare providers to determine the best course of action.

From the Research

Methotrexate and Total Knee Replacement Surgery

• The decision to stop methotrexate before total knee replacement surgery is a complex one, with various factors to consider, including the risk of infection and the patient's overall health 2.
• A study published in 1991 found that patients with rheumatoid arthritis who continued taking methotrexate until less than 4 weeks before surgery had a higher rate of complications, including prosthetic joint infection or wound dehiscence or infection, compared to those who discontinued methotrexate 4 weeks before surgery 2.
• Another study published in 2020 found that short-term discontinuation of methotrexate for up to 2 weeks is safe, whereas discontinuation for 4 weeks is associated with a transient increase in disease flares and activity in RA patients taking a stable methotrexate dose 3.

Infection Risk and Methotrexate

• The risk of infection is a major concern when considering whether to stop methotrexate before total knee replacement surgery 2, 4.
• A study published in 2023 found that patients taking prednisone after total joint arthroplasty were at increased risk of periprosthetic joint infection, but no dose-dependent relationship was identified 4.
• Another study published in 2025 found that robotic-assisted total knee replacement and conventional total knee replacement have similar infection rates, with an overall surgical site infection rate of 1.57% in conventional TKR and 1.29% in RA-TKR 5.

Considerations for Methotrexate Discontinuation

• When deciding whether to stop methotrexate before total knee replacement surgery, healthcare providers should consider the individual patient's risk factors, including their overall health, disease activity, and medication regimen 2, 3.
• The potential benefits of discontinuing methotrexate, such as reducing the risk of infection, must be weighed against the potential risks, including an increase in disease activity and flares 3.