How should Actemra (Tocilizumab) be managed with regards to wound healing, specifically incisional healing and bone fracture healing?

From the Guidelines

Actemra (tocilizumab) should be temporarily discontinued before elective surgery and during the initial healing phase to minimize risks of delayed wound and bone healing, with treatment resumed once the wound shows evidence of healing, typically around 14 days after surgery, as conditionally recommended by the 2022 American College of Rheumatology guideline 1.

Management Considerations

When managing Actemra in the context of wound healing, several factors must be considered:

• The timing of discontinuation before surgery, which may vary depending on the formulation (subcutaneous or intravenous) and the type of surgical procedure.
• The clinical status of the patient, including the severity of their rheumatic condition and their overall health.
• The status of the healing wound, with consideration of signs such as swelling, erythema, drainage, and the presence of any infection.

Resumption of Therapy

The decision to restart Actemra therapy should be based on the clinical assessment of the patient and the wound healing progress, as indicated by the absence of significant swelling, erythema, or drainage, and no ongoing nonsurgical site infection 1. For patients undergoing elective total hip or total knee arthroplasty, antirheumatic therapy, including Actemra, should be restarted once these conditions are met, typically around 14 days after surgery.

Special Considerations for Bone Fracture Healing

While the guideline primarily addresses wound healing in the context of surgical incisions, the principles can be extended to bone fracture healing, where the role of inflammation in the healing process is critical. Actemra, by inhibiting IL-6 signaling, may potentially delay bone healing, suggesting that a longer delay in resuming therapy (4-6 weeks) after fractures or orthopedic procedures might be prudent to allow initial bone healing, although this is not directly addressed in the provided guideline.

Monitoring and Individualized Care

Close monitoring for signs of delayed healing or infection is crucial after resuming Actemra treatment. The decision to restart therapy should be individualized, taking into account the patient's specific condition, the complexity of the surgical procedure, and the risk of infection, to balance the benefits of controlling rheumatic disease activity with the potential risks to wound and bone healing.

From the Research

Management of Actemra (Tocilizumab) with regards to Wound Healing

• The management of Actemra (Tocilizumab) in patients undergoing surgery, particularly with regards to wound healing, is crucial to prevent complications 2, 3.
• Studies have shown that patients treated with Tocilizumab may have a higher risk of wound healing concerns, including delayed wound healing and postoperative infections 2, 3.
• The incidence of delayed wound healing was found to be significantly higher in patients who underwent spinal surgery while being treated with Tocilizumab 3.

Incisional Healing

• Negative pressure wound therapy (NPWT) has been shown to be effective in managing and accelerating healing of closed incisional wounds, reducing the incidence of wound healing complications 4.
• The use of NPWT has been found to reduce haematoma and seroma, accelerate wound healing, and increase clearance of oedema 4.
• However, there is limited evidence on the use of NPWT in patients treated with Tocilizumab, and further studies are needed to determine its effectiveness in this population.

Bone Fracture Healing

• Infection is a common cause of impaired fracture healing, and the ability to treat infection while promoting fracture healing is crucial to reduce the cost, number of procedures, and patient morbidity associated with infected fractures 5.
• The treatment of fracture healing and infection often requires a sequential approach, with different clinical specialties addressing the problem, which can lead to increased morbidity and prolonged treatment duration 5.
• There is a need for new therapies that can address both fracture healing and infection simultaneously, and further research is needed to develop effective treatments for this clinical challenge 5.

Perioperative Management of Tocilizumab

• The perioperative management of Tocilizumab in patients undergoing orthopaedic surgery is crucial to prevent complications, including delayed wound healing and postoperative infections 2, 3.
• The TOcilizumab in Perioperative Period (TOPP) study found that patients treated with Tocilizumab had a higher incidence of delayed wound healing, particularly after spinal surgery 3.
• The study also found that increased postoperative C-reactive protein (CRP) levels were observed in patients without postoperative events when the duration from final Tocilizumab infusion to surgery was long, highlighting the importance of monitoring CRP levels and postoperative conditions in patients treated with Tocilizumab 3.