Risk of Serious Infection Lower With Belimumab Than Oral Immunosuppressants When Treating Nonrenal Systemic Lupus Erythematosus
Key findings
- This large, observational cohort study, designed to emulate a randomized trial, compared the risk of serious infection among patients with nonrenal systemic lupus erythematosus who used belimumab vs. azathioprine, mycophenolate or methotrexate
- The incidence of serious infections and hospitalizations for infections was substantial in all groups; for example, 7% to 16% of patients required hospitalization for serious infection within five years of initiating therapy
- Belimumab use was associated with a 21% lower risk of serious infection over five years compared with any of the three comparator drugs
- Initiation of belimumab was associated with less risk of hospitalization for serious infection compared with initiation of azathioprine (27% lower risk) or mycophenolate (44% lower risk) but not methotrexate
- In pooled analysis, belimumab use was associated with 23% lower risk of hospitalization for serious infection compared with any of the three comparator drugs
Systemic lupus erythematosus (SLE) increases the risk of serious infections, heightened even more by immunosuppressive therapy.
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Researchers at Massachusetts General Hospital have now become the first to address the knowledge gap of how infection risk might differ between belimumab and common oral immunosuppressants when used to treat SLE.
In a large observational study that simulated a randomized trial, the risk of serious infection was lower with belimumab than with azathioprine, methotrexate or mycophenolate. Emma Materne, MD, a medicine-pediatrics resident in the Department of Medicine, April Jorge, MD, a rheumatologist in the Division of Rheumatology, Allergy & Immunology, and colleagues report in Arthritis & Rheumatology.
Methods
The data source for the study was Tri-NetX. This database includes electronic health records from 46 healthcare organizations across the U.S., representing a variety of practice types and both rural and urban areas.
21,481 adults were identified who had nonrenal SLE at the time of initiating one of the four drugs of interest between 2011 and 2021. Lupus nephritis was excluded because it increases the risk of serious infection.
To emulate a randomized trial, the researchers created three comparator groups that were similar concerning demographics, geographic region, year of treatment initiation, chronic kidney disease, Charlson comorbidity index, SLE severity, use of concomitant SLE medications, healthcare utilization, and infection history in the prior six months:
- Belimumab (n=2,841) vs. azathioprine (n=6,343)
- Belimumab (n=2,642) vs. methotrexate (n=8,242)
- Belimumab (n=2,813) vs. mycophenolate (n=8,407)
Primary Outcome
The primary outcome was serious infection, defined as bacteremia, pneumonia, skin/soft-tissue infection, osteomyelitis, meningitis, or gastrointestinal infection. Five years after treatment initiation, the cumulative incidence of serious infection was:
- Belimumab vs. azathioprine—30% vs. 35% (adjusted HR [aHR], 0.82; 95% CI, 0.72–0.92)
- Belimumab vs. methotrexate—27% vs. 30% (aHR, 0.86; 95% CI, 0.76–0.97)
- Belimumab vs. mycophenolate—32% vs. 41% (aHR, 0.69; 95% CI, 0.61–0.78)
- Belimumab vs. any of the three comparators—aHR, 0.79 (95% CI, 0.71–0.87)
Secondary Outcome
The secondary outcome was hospitalization for serious infection. At five years the cumulative incidence was:
- Belimumab vs. azathioprine—8% vs. 10% (aHR, 0.73; 95% CI, 0.57–0.94)
- Belimumab vs. methotrexate—6.7% vs. 6.6% (aHR, 1.02; 95% CI, 0.79–1.33)
- Belimumab vs. mycophenolate—10% vs. 16% (aHR, 0.56; 95% CI, 0.43–0.71)
- Belimumab vs. any of the three comparators—aHR, 0.73 (95% CI, 0.59–0.91)
Control Outcome
As a control, the researchers examined how the use of belimumab or oral immunosuppressants affected the risk of traumatic injury. As expected, belimumab had no protective effect, which improves confidence that the main findings represent a truly lower risk of infection with the drug.
The study results should inform risk/benefit considerations for SLE treatment.
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