Immune system and Biologics

DMARDs & immunosuppressants

Cytokine Modulators (Immunosuppressants)

NB: These agents are also sometimes referred to as Disease Modifying Anti-Rheumatic Drugs (DMARDs) or ‘Biologics’

If the patient is taking one of these medications for a rheumatological indication, ideally the surgical team and patient’s rheumatologist should be involved in the planning for elective surgery1. The potential prevention of post-operative infection by stopping biologics should be balanced against the risk of perioperative flare in disease activity

For most biologics, except rituximab and tocilizumab, surgery should ideally be planned for when at least one dosing interval has elapsed for that drug.

Discuss with the patient’s consultant who has prescribed the medication for advice if there is any doubt or ambiguity as to how to proceed (e.g. in rare but complex cases such as connective tissue disease and vasculitis). See below for specific advice.

The following advice is in line with recommendations by the American College of Rheumatology and American Association of Hip and Knee Surgeons2.

Examples: Abatacept, Adalimumab, Anakinra, Baricitinib, Belimumab, Brodalumab, Certolizumab, Dupilumab, Etanercept, Golimumab, Guselkumab, Infliximab, Ixekizumab, Risankizumab, Rituximab, Sarilumab, Secukinumab, Tildrakizumab, Tocilizumab, Tofacitinib, Ustekinumab, Vedolizumab

Specific agents

Methotrexate

Continue this medication pre-operatively.

Sulfasalazine

Continue this medication pre-operatively.

Hydroxychloroquine

Continue this medication pre-operatively.

Leflunomide (Arava)

Continue this medication pre-operatively.

Doxycycline

Continue this medication pre-operatively.

Apremilast

Continue this medication pre-operatively.

Mycophenolate

  • If this is prescribed for severe SLE, continue as normal.
  • If this is prescribed for anti-rejection due to an organ transplant, continue but consult the patient’s specialist to confirm.
  • For other indications, surgery should be at least 1 week after last dose.

Azathioprine

  • If this is prescribed for severe SLE, continue as normal.
  • If this is prescribed for anti-rejection due to an organ transplant, continue but consult the patient’s specialist to confirm.
  • For other indications, surgery should be at least 1 week after last dose.

Cyclosporine (systemic)

  • If this is prescribed for severe SLE, continue as normal.
  • If this is prescribed for anti-rejection due to an organ transplant, continue but consult the patient’s specialist to confirm.
  • For other indications, surgery should be at least 1 week after last dose.

Tacrolimus

  • If this is prescribed for severe SLE, continue as normal.
  • If this is prescribed for anti-rejection due to an organ transplant, continue but consult the patient’s specialist to confirm.
  • For other indications, surgery should be at least 1 week after last dose.

Rituximab (Rituxan)

Surgery should be delayed until at least 3 months post-infusion (infusions are usually every 6 months).

Belimumab (Benlysta)

  • If this is prescribed for severe SLE, continue:
    • If administered subcutaneously (doses usually weekly) continue as normal
    • If administered intravenously (usually ever 4 weeks), plan surgery for the 4th week after the last dose.
  • For other indications
    • If administered subcutaneously, usually given at 1 week intervals. In this case, one dose should be held, so the surgery should take place in the second week after the last dose.
    • If administered intravenously, usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

Tocilizumab (Actemra)

  • If administered subcutaneously, usually given at 1 week intervals. In this case, one dose should be held, so the surgery should take place in the second week after the last dose.
  • If administered intravenously, usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

Anifrolumab (Saphnelo)

This is usually given intravenously at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

Voclosporin (Lupkynis)

Continue this medication pre-operatively.

Infliximab (Remicade)

Usually given every 4, 6, or 8 weeks. Withhold one dose, and plan surgery to take place in the week after this missed dose (for example, if given every 4 weeks, withhold one dose and ideally have surgery during the fifth week after the last dose).

Adalimumab (Humira)

Usually given every 2 weeks. Withhold one dose, and plan surgery to take place in the week after this missed dose (for example, if given every 2 weeks, withhold one dose and ideally have surgery during the third week after the last dose).

Etanercept (Enbrel)

Usually given weekly. Withhold one dose, and plan surgery to take place in the week after this missed dose (for example, if given weekly, withhold one dose and ideally have surgery during the second week after the last dose).

Golimumab (Simponi)

  • If administered subcutaneously, usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.
  • If administered intravenously, usually given at 8 week intervals. In this case, one dose should be held, so the surgery should take place in the ninth week after the last dose.

Abatacept (Orencia)

  • If administered subcutaneously, usually given at 1 week intervals. In this case, one dose should be held, so the surgery should take place in the second week after the last dose.
  • If administered intravenously, usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

Certolizumab (Cimzia)

Usually given every 2 or 4 weeks. Withhold one dose, and plan surgery to take place in the week after this missed dose (for example, if given every 4 weeks, withhold one dose and ideally have surgery during the fifth week after the last dose).

Anakinra (Kineret)

Withhold one day before surgery.

IL-17-Secukinumab (Cosentyx)

This is usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

Ustekinumab (Stelara)

This is usually given at 12 week intervals. In this case, one dose should be held, so the surgery should take place in the thirteenth week after the last dose.

Ixekizumab (Taltz)

This is usually given at 4 week intervals. In this case, one dose should be held, so the surgery should take place in the fifth week after the last dose.

IL-23 Guselkumab (Tremfya)

This is usually given at 8 week intervals. In this case, one dose should be held, so the surgery should take place in the ninth week after the last dose.

Tofacitinib (Xeljanz)

Withhold 3 days prior to surgery.

Baricitinib (Olumiant)

Withhold 3 days prior to surgery.

Upadacitinib (Rinvoq)

Withhold 3 days prior to surgery.

Mercaptopurine (6-Mercaptopurine)

Continue this medication pre-operatively.

Anti-Rejection Medication for Transplants

Continue – the patient’s relevant specialist should be involved in the planning for surgery except sirolimus – consult with the patient’s relevant specialist at the earliest opportunity when planning for surgery so that a management plan can be made. Some are specifically outlineed above.

Examples: Azathioprine, Ciclosporin, Mycophenolate mofetil, Sirolimus, Tacrolimus

References

1.
Holroyd CR, Seth R, Bukhari M, et al. The british society for rheumatology biologic DMARD safety guidelines in inflammatory arthritis. Rheumatology. 2019;58(2):e3-e42.
2.
Goodman SM, Springer BD, Chen AF, et al. 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. Arthritis Care & Research. 2022;74(9):1399-1408. doi:10.1002/acr.24893