Serious lupus infection risk lower with belimumab vs. oral immunosuppressants

November 13, 2022

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Materne E. Abstract 349. Presented at: ACR Convergence 2022; Nov. 11-14, 2021; Philadelphia (hybrid meeting).

Disclosures: Materne reports no relevant financial information.

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PHILADELPHIA – Patients with extrarenal lupus erythematosus receiving belimumab show reduced risk of serious infection compared with. those treated with oral immunosuppressive drugs, according to data presented at the ACR Convergence 2022.

“Lupus patients are already at increased risk for infection because of the disease process and how it modifies the immune system, and then you combine that with an additional oral immunosuppressant like azathioprine, or steroids, or methotrexate, and that puts them at even more risk on serious infections,” Emma Motherdoctor, internal medicine and pediatrics resident at Massachusetts General Hospital, in Boston, said at a press conference.

Patients with extrarenal SLE receiving belimumab show a reduced risk of serious infection compared with. those treated with oral immunosuppressive drugs, according to data presented at the ACR Convergence 2022. Source: Adobe Stock

“In general, patients with lupus have about a 50% chance of developing a serious bacterial infection in their lifetime, with up to a quarter of their hospital admissions being infection-related,” she added. “Some previous studies of belimumab have shown that when you add it to an oral immunosuppressant, there is no increased rate of infections, but this is compared to a placebo.” There have been no other head-to-head analyzes looking at the risk of infection when starting belimumab vs. oral immunosuppressive drugs, especially methotrexate, mycophenolate or azathioprine.

To analyze how medications used to treat SLE may affect the risk of infection, Materne and colleagues looked at data from TriNetX, a multicenter EHR database spanning 46 health care facilities across the United States. The researchers included adults with SLE who started belimumab (Benlysta, GlaxoSmithKline), azathioprine, methotrexate, or mycophenolate between 2011 and 2021 and did not have index nephritis.

Materne and colleagues designed three hypothesis-driven studies that estimated the cumulative incidence and HR for serious infection, as well as hospitalization for serious infection, separately comparing belimumab vs. azathioprine, belimumab vs. methotrexate and belimumab vs. mycophenolate. For each comparison, patients had never used the control drugs but could use other immunosuppressive drugs. For example, methotrexate or mycophenolate could be used in belimumab vs. azathioprine comparison.

For each analysis, the researchers simulated randomization using overlapping propensity score weighting to balance for covariates including age, sex, race, ethnicity, geographic region, year of onset, 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 previous infection history.

Materne and colleagues followed these patients until severe infection, hospitalization for severe infection, death, or the end of the study period. They adjusted for treatment group adherence using inverse probability of treatment weighting and repeated the analysis with a negative control injury/injury outcome.

A total of 2,841 and 6,343 belimumab pioneers vs. azathioprine, 2,642 and 8,242 belimumab and methotrexate adopters, and 2,813 and 8,407 belimumab and mycophenolate initiates, respectively. In each comparison, all covariates were balanced by propensity score overlap. Glucocorticoids were used in 56% of patients.

According to the investigators, belimumab was associated with lower rates of serious infection (HR = 0.81; 95% CI, 0.72-0.92) and hospitalization for serious infection (HR = 0.73; 95% CI, 0.57-0.94 ), compared to azathioprine. through 5 years. The researchers reported similar results for other drug comparisons. Meanwhile, there was no difference in the risk of injury or trauma.

“What’s new or innovative about our study is that this is the first head-to-head comparison that looks at starting belimumab versus starting methotrexate, or mycophenolate, or azathioprine,” Materne said. “I think another strength 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 group, which is more than other previous studies in lupus patients . We also looked at data spanning various regions of the United States—every region was included, and this makes our data completely generalizable to lupus patients and clinical practice.

“I think something to consider going forward is that these data could inform our decision to start a patient with belimumab, possibly earlier, as opposed to another immunosuppressive drug, and I think the next steps in our work may be looking at why we see this reduction in infection risk in patients on belimumab,” she added. “Is it because of a more specific effect that belimumab has on the immune system, possibly reducing the severity of the disease, or that we might see a steroid-sparing effect in patients who are on belimumab?”

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