From the Guidelines
Methotrexate can be safely continued in the perioperative period for patients undergoing elective orthopaedic surgery, as the benefits of preventing rheumatoid arthritis flares often outweigh the minimal risks to wound healing. The effects of methotrexate (MTX) on wound healing are complex, involving the inhibition of folate metabolism and cell proliferation, which can reduce fibroblast activity and collagen synthesis 1. However, the clinical significance of these effects is generally modest when MTX is used at typical rheumatological doses.
Key Considerations
- The decision to continue or stop MTX should be individualized based on the patient's disease activity, surgical complexity, and comorbidities.
- For patients undergoing elective orthopaedic surgery, the evidence suggests that continuing MTX does not significantly increase the risk of wound morbidity 1.
- Ensuring adequate nutrition, particularly folate supplementation, may help mitigate some of MTX's negative effects on wound healing.
- In cases of major surgeries or when patients have additional risk factors for poor wound healing (such as diabetes, malnutrition, or concurrent corticosteroid use), a temporary hold of MTX may be considered, but this should be decided on a case-by-case basis.
Clinical Implications
The continuation of methotrexate in the perioperative period for elective orthopaedic surgery is supported by studies showing no significant difference in postoperative complications between patients who continued or stopped MTX 1. Furthermore, continuing MTX can reduce the risk of rheumatoid arthritis flares, which is a significant consideration in the management of these patients. Therefore, unless there are specific concerns that outweigh the benefits of continued MTX therapy, it is generally recommended to continue methotrexate in the perioperative period to balance the risks of wound healing impairment against the need to control underlying disease activity.
From the FDA Drug Label
Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. The FDA drug label does not answer the question.
From the Research
Effect of Methotrexate on Wound Healing
- Methotrexate (MTX) is a disease-modifying drug used to treat a wide range of conditions, and its effect on wound healing has been studied in various experiments and clinical trials 2, 3.
- In vitro and experimental animal studies suggest that MTX can adversely affect wound healing, whilst clinical studies show that low-dose MTX is safe and does not affect the incidence of postoperative wound complications 2.
- A study on rats found that MTX dose-dependently decreased the degree of inflammation and angiogenesis, tissue hydroxyproline level, and HSP70 and tumor necrosis factor-α expression in the early phase of wound healing, and suppressed epithelialization and collagen 1 expression throughout the wound-healing process 3.
- The same study found that wounds treated with high-dose MTX had statistically delayed wound closure compared to the saline group, while wounds treated with low-dose MTX only had statistically delayed wound closure on day 14 3.
Comparison of Low-Dose and High-Dose Methotrexate
- Low-dose MTX has been found to be safe and effective for treating adult and juvenile rheumatoid arthritis, and does not significantly affect bone formation during fracture healing 4.
- High-dose MTX, on the other hand, may delay the progress of new periosteal bone formation and has been found to have a dose-dependent adverse effect on wound healing 3, 4.
Immunosuppressive Therapy and Wound Healing
- Immunosuppressive therapy, including MTX, can affect wound healing to varying degrees, and may increase the risk of post-operative infections and wound-healing complications 5, 6.
- The effects of immunosuppressive therapy on wound healing are complex and depend on various factors, including the type and dose of medication, and the individual patient's condition 5, 6.