Belimumab vs. Oral Immunosuppressants: Infection Risk in Patients with Non-Renal SLE

Background & Objectives

Infection is a leading cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE). Around half of patients with SLE will have at least one serious infection during the course of their disease, and 11–23% of hospitalizations in patients with SLE are related to infection. Treatment with immunosuppressive therapy, including glucocorticoids and steroid-sparing immunosuppressants, is associated with an increased risk for infection.

Materne et al. aimed to compare the risk of infection among patients with non-renal SLE using the injectable immunosuppressant belimumab vs. an oral immunosuppressant, azathioprine, mycophenolate or methotrexate.

Prior studies of patients with SLE showed increased risks for infection and hospitalization in patients initiating oral immunosuppressant therapy (e.g., methotrexate, azathioprine or mycophenolate) compared to those using hydroxychloroquine.

Methods

Patients were identified from TriNetX, a federated electronic health record database including 100 healthcare organizations across the U.S., representing academic medical centers, specialty physician practices and community hospitals. The researchers identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate or mycophenolate between 2011 and 2021.

Materne et al. designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios of serious infection and hospitalization for serious infection, comparing belimumab with each oral immunosuppressant. In three parallel arms, they separately compared initiation of belimumab with azathioprine, belimumab with methotrexate, and belimumab with mycophenolate.

Results

Among 21,481 patients, the researchers compared 2,841 and 6,343 initiators of belimumab and azathioprine, 2,642 and 8,242 initiators of belimumab and methotrexate, and 2,813 and 8,407 initiators of belimumab and mycophenolate, respectively.

Compared with azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection and hospitalization for infection. The risk of infection was also lower with belimumab than with methotrexate.

Conclusion

Materne et al.found that belimumab use was associated with a lower risk for serious infection in patients with non-renal SLE than other oral immunosuppressants, azathioprine, methotrexate and mycophenolate. Initiation of belimumab was associated with a lower risk of hospitalization for serious infection compared with initiation of azathioprine or mycophenolate, but not methotrexate.

For complete details, including source material, refer to the full study.   

Excerpted and adapted from:

Materne E, Choi H, Zhou B, et al. Comparative risks of infection with belimumab versus oral immunosuppressants in patients with non-renal systemic lupus erythematosus. Arthritis Rheumatol. 2023 Nov;75(11).