Severe infection risk for lupus lower with belimumab vs. oral immunosuppressants
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PHILADELPHIA — Patients with non-renal systemic lupus erythematosus who receive belimumab demonstrate a lower risk for severe infection vs. those treated with oral immunosuppressants, according to data presented at ACR Convergence 2022.
“Patients with lupus are already at an increased risk for infection because of the disease process and how it modulates the immune system, and then you combine that with an additional oral immunosuppressant such as azathioprine, or steroids, or methotrexate, and that puts them at even further risk for severe infections,” Emma Materne, MD, an internal medicine and pediatrics resident at Massachusetts General Hospital, in Boston, said during a press conference.
“In general, patients with lupus have about a 50% chance of having a serious bacterial infection within their lifetime, with up to a quarter of their hospitalizations related to infection,” she added. “Some previous work in belimumab has shown that when you add it to oral immunosuppressants, there is no increased incidence of infection, but this is compared to placebo. There have not been any other head-to-head analyses looking at the risk for infection when you initiate belimumab vs. oral immunosuppressants, specifically methotrexate, mycophenolate or azathioprine.”
To analyze how medications used to treat SLE can impact the risk for infection, Materne and colleagues examined data from TriNetX, a multi-center EHR database spanning 46 health care organizations across the United States. The researchers included adults with SLE who initiated belimumab (Benlysta, GlaxoSmithKline), azathioprine, methotrexate or mycophenolate between 2011 and 2021 and who did not have lupus nephritis prior to the index date.
Materne and colleagues designed three hypothetical trials estimating the cumulative incidence and HRs for severe infection, as well as hospitalization for severe infection, specifically comparing belimumab vs. azathioprine, belimumab vs. methotrexate and belimumab vs. mycophenolate. For each comparison, patients had never used the comparator drugs but could use other immunosuppressants. For example, methotrexate or mycophenolate could be used in the belimumab vs. azathioprine comparison.
For each analysis, the researchers simulated randomization using propensity score overlap weighting to balance covariates, including age, sex, race, ethnicity, geographic region, year of initiation, use of concomitant SLE medications — including other oral immunosuppressants, glucocorticoids, hydroxychloroquine, rituximab (Rituxan, Genentech) and cyclophosphamide — Charlson comorbidity index, SLE severity index, chronic kidney disease, health care use and prior infection history.
Materne and colleagues followed these patients until severe infection, hospitalization for severe infection, death or end of the study period. They adjusted for adherence to treatment group using inverse probability of treatment weighting, and repeated the analysis with the negative control outcome of injury/trauma.
In all, the comparisons included 2,841 and 6,343 initiators of belimumab vs. azathioprine, 2,642 and 8,242 users of belimumab and methotrexate, and 2,813 and 8,407 initiators of belimumab and mycophenolate, respectively. In each comparison, all covariates were balanced after propensity score overlap weighting. Glucocorticoids were used in 56% of patients.
According to the researchers, belimumab was associated with a lower incidence of severe infection (HR = 0.81; 95% CI, 0.72-0.92) and hospitalization for severe infection (HR = 0.73; 95% CI, 0.57-0.94), compared with azathioprine through 5 years. The researchers reported similar findings for the other medication comparisons. Meanwhile, there was no difference in the risk for injury or trauma.
“What is new or novel about our study is that it is the first direct comparison looking at initiating belimumab as opposed to initiating methotrexate, or mycophenolate or azathioprine,” Materne said. “I think some other strengths of our study is that we had a very large number of patients — more than 21,000 — as well as a very high percentage of African-American patients — 28% in our cohort, which is greater than other previous studies in lupus patients. We also looked at data spanning across various regions in the United States — every region was included, and this makes our data quite generalizable to patients with lupus and clinical practice.
“I think, going forward, something to consider is that this data may inform our decision to start belimumab in a patient potentially earlier, as opposed to another immunosuppressant medication, and I think next steps for our work might be looking at why we see this attenuation in infection risk in patients on belimumab,” she added. “Is it because of the more specific effects that belimumab has on the immune system, potentially that it decreases disease severity, or that we may be seeing a steroid sparing effect on patients who are on belimumab?”
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Materne E. Abstract 349. Presented at: ACR Convergence 2022; Nov. 11-14, 2021; Philadelphia (hybrid meeting).
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