When should mycophenolate mofetil (MMF) and prednisone be held in a patient with Systemic Lupus Erythematosus (SLE)?

When to Hold Mycophenolate Mofetil and Prednisone in SLE

For patients with non-severe SLE undergoing elective surgery, hold mycophenolate mofetil 1 week prior to surgery and restart once the wound shows evidence of healing (typically ~14 days); for patients with severe SLE, continue mycophenolate mofetil through surgery; prednisone should be continued at the current daily dose rather than held or increased perioperatively. 1, 2

Perioperative Management for Elective Surgery

Non-Severe SLE

• Withhold mycophenolate mofetil 1 week (7 days) before elective total hip or knee arthroplasty to permit return of some immune function while balancing the risk of prosthetic joint infection against disease flare 1, 2, 3
• This recommendation applies to patients without vital organ-threatening disease who can tolerate a potential flare without risk of permanent organ damage 1
• Patients with frequent flares or difficult-to-control SLE may continue medications through a shared decision-making approach, though most can be monitored closely post-surgery 1

Severe SLE

• Continue mycophenolate mofetil at the usual dose through the surgical period in patients with severe SLE (defined as vital organ-threatening disease) 1, 2, 3
• The concern about disease flares and risk of organ damage in severe SLE outweighs perioperative infection risk 1
• Exceptions include patients with severe SLE who have been stable for >6 months or who have a history of recurrent or severe infections—these patients may discontinue medications perioperatively 1

Restarting After Surgery

• Resume mycophenolate mofetil once the wound shows evidence of healing, typically at ~14 days post-surgery 1, 2, 3
• Specific criteria for restarting: sutures/staples are removed, no significant swelling/erythema/drainage present, and no evidence of surgical site or non-surgical site infection 1, 3

Prednisone Management Perioperatively

• Continue the current daily dose of prednisone through surgery rather than holding or administering supraphysiologic stress doses 1, 2
• This applies to all SLE patients (both severe and non-severe) receiving glucocorticoids for their rheumatic condition 2
• The outdated practice of stress-dose steroids is not recommended based on current evidence 1

Pregnancy Considerations

Mycophenolate mofetil must be avoided during pregnancy due to teratogenic effects including increased risk of miscarriage, stillbirth, premature delivery, and fetal malformations 4

• Discontinue mycophenolate mofetil before conception in women planning pregnancy 4
• Safe alternatives during pregnancy include prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 4

Infection Context

Active Infection

• Hold mycophenolate mofetil during active serious infections until the infection is adequately treated 5
• The immunosuppressive effects increase infection risk, particularly serious infections 6

COVID-19 Pandemic Guidance

• In stable SLE without infection or known SARS-CoV-2 exposure, mycophenolate mofetil may be continued 5
• For patients with systemic inflammatory or vital organ-threatening disease (e.g., lupus nephritis), mycophenolate mofetil may be initiated even during the pandemic if clinically indicated 5

Long-Term Maintenance Considerations

Duration of Therapy

• The total duration of immunosuppression (initial plus maintenance) for proliferative lupus nephritis should be ≥36 months before considering withdrawal 7
• For patients who achieve complete renal response with proteinuria <0.5 g/day maintained for 2-3 years, mycophenolate mofetil withdrawal can be considered 7, 8

Withdrawal in Quiescent Disease

• Recent evidence suggests mycophenolate mofetil withdrawal in patients with stable, quiescent SLE (clinical SLEDAI <4 for ≥1-2 years) results in only a modest increase in disease reactivation risk (approximately 7% absolute increase) 8
• The decision to withdraw should balance the risk of flare against the benefits of reducing infection risk and medication toxicity 8
• Withdrawal should be gradual (tapered over 12 weeks) rather than abrupt 8

Common Pitfalls to Avoid

• Do not abruptly discontinue mycophenolate mofetil in patients on long-term therapy—taper gradually to minimize withdrawal flares 8
• Do not give stress-dose steroids perioperatively—continue the baseline prednisone dose 1, 2
• Do not restart immunosuppression too early after surgery—wait for clear evidence of wound healing to minimize infection risk 1, 3
• Do not continue mycophenolate mofetil in pregnancy—this is an absolute contraindication 4
• Consult the patient's rheumatologist before making perioperative medication decisions in severe SLE, as individual risk-benefit assessment is critical 1