When to Stop Benlysta (Belimumab) in SLE
Belimumab should generally not be stopped in patients with SLE who have achieved disease stability, as discontinuation significantly increases the risk of disease flares, elevated disease activity scores, increased glucocorticoid requirements, and new organ involvement. 1, 2
Evidence Against Routine Discontinuation
Risk of Disease Flares and Rebound
Discontinuing belimumab after achieving disease stability leads to increased SLEDAI-2000 scores, enhanced immunological marker activity, and only 20% of patients maintaining low disease activity state (LLDAS) at 6 months, compared to 76.67% who continue treatment. 2
Severe disease flares affecting previously uninvolved major organ systems have been reported after belimumab cessation, including new-onset lupus nephritis, severe pneumonitis, and CNS involvement—suggesting a potential rebound phenomenon. 3
Even temporary 24-week discontinuation in patients with stable low disease activity resulted in flare rates of 1.0 per patient-year during the withdrawal period, compared to 0.3 after restarting treatment. 4
Guideline Recommendations for Continuation
The KDIGO 2024 guidelines explicitly recommend that patients with lupus nephritis on belimumab-containing triple therapy should continue with triple therapy as maintenance for at least 3 years after achieving response. 1
The American College of Rheumatology emphasizes that discontinuation of successful treatment regimens in patients with severe SLE carries significant risk of disease flares and potential organ damage. 1
The EULAR 2024 guidelines note that belimumab demonstrated superior efficacy to standard of care in high-quality randomized controlled trials for both extrarenal disease and lupus nephritis. 5
Rare Circumstances Where Discontinuation May Be Considered
Stringent Criteria for Potential Discontinuation
If discontinuation is contemplated despite the risks, patients must meet ALL of the following criteria based on available evidence: 6
- SELENA-SLEDAI score < 4 (ideally 0-2) 6
- Prednisolone dose < 5 mg/day (ideally ≤ 3 mg/day) 6
- Normalized complement levels (C3 and C4 in normal range) 6
- Negative or very low anti-dsDNA antibodies (< 10 IU/mL) 6
- Sustained remission for prolonged duration (data suggest at least 12+ months of stability) 7, 6
- No history of major organ involvement (particularly lupus nephritis or CNS disease) 1, 3
Important Caveats
Even among patients meeting these stringent criteria, 50% experienced relapse within 52 weeks of discontinuation in one study. 6
Patients who discontinued belimumab required significantly higher glucocorticoid doses (9.5 mg/day vs. 3.0 mg/day in those who remained flare-free). 6, 2
The duration of immunosuppressive therapy should account for timing and magnitude of response, duration of flare-free maintenance, and extrarenal SLE activity. 5
Preferred Management Strategy
Continue Belimumab Indefinitely
Most patients with lupus nephritis require ≥ 3 years of maintenance immunosuppression, and belimumab-treated patients demonstrate sustained efficacy through 104-128 weeks with no increase in adverse events. 1
Belimumab enables glucocorticoid tapering and discontinuation while maintaining disease control—over 20% of patients discontinued corticosteroids entirely while continuing belimumab. 7
The BLISS-LN trial open-label extension showed maintained benefit at 128 weeks with no safety concerns, supporting long-term continuation. 1
Gradual Tapering Approach (If Absolutely Necessary)
If discontinuation is pursued despite recommendations, gradual immunosuppressive drug tapering is recommended prior to complete withdrawal, with glucocorticoids tapered first. 5
Close monitoring is essential: patients should be assessed for rising SLEDAI scores, declining complement levels, rising anti-dsDNA antibodies, and new symptoms every 4-8 weeks after discontinuation. 6, 2
Common Pitfalls to Avoid
Do not discontinue belimumab simply because the patient has achieved remission—this is when the drug is working and should be continued to maintain that remission. 1, 2
Do not assume that stable disease off glucocorticoids means belimumab can be stopped—the belimumab itself may be maintaining that glucocorticoid-free state. 7, 2
Do not discontinue in patients with lupus nephritis who have achieved complete renal response—these patients specifically benefit from continued triple therapy including belimumab. 1
Avoid abrupt discontinuation—if stopping is deemed necessary, ensure very close monitoring for early signs of flare. 3, 4