Serious Infection Risk High in Patients With Lupus Save

Patients with systemic lupus erythematosus (SLE) had two to four times higher risk for serious infection requiring hospitalization, a nationwide Swedish study found.

In a multivariate analysis that adjusted for age, sex, region of residence, and education, the hazard ratio for serious infection among SLE patients compared with the general population was 4.11 (95% CI 3.66-4.61), according to Julia F. Simard, ScD, of Stanford University in California, and colleagues from the Karolinska Institute in Stockholm.

And even after further adjustment for comorbidities and recent medication use, the hazard ratio remained elevated, at 1.88 (95% CI 1.58-2.23), the researchers reported online in Lupus Science & Medicine.

Patients with SLE are known to be susceptible to serious infections because of their immune system dysregulation, including impaired functioning of B and T cells and low levels of complement, as well as the use of immune-suppressing medications such as corticosteroids and cyclophosphamide.

However, little is known about the risks associated with commonly used disease-modifying antirheumatic drug (DMARD) therapies such as azathioprine or mycophenolate mofetil (Cellcept).

Therefore, to clarify the rates of hospitalized infections and consider the influence of DMARDs, Simard and co-authors identified 2,378 incident SLE patients in Swedish registries from 2006 to 2013 who were matched with 11,774 individuals from the general population.

Medication use was ascertained from the Swedish Prescribed Drug Register. Included patients were classified as hydroxychloroquine initiators or initiators of azathioprine, methotrexate, or mycophenolate; other DMARDs such as sulfasalazine or cyclophosphamide were rarely given, so users of these agents were not included. In addition, the drug register does not include medications given by infusion in a hospital setting, so these patients also were excluded.

Patients' mean age was 49, and 85% were women.

During a median follow-up of 6.4 years, serious infections occurred in 22% of the SLE group compared with 6% of the control group. In both groups, pneumonia was the diagnosis in one-quarter of patients.

In the SLE group, the rate of serious infections was 40 per 1,000 person-years compared with 10 per 1,000 in the general population, for a rate difference of 30.1 per 1,000 (95% CI 26.7-33.8).

The SLE group also had a twofold higher risk for recurrent hospitalizations for infection (HR 2.22, 95% CI 1.93-2.56). The risk was highest during the first year, but remained elevated throughout follow-up.

Between 2006 and 2016, 392 patients started on the antimalarial hydroxychloroquine and 387 initiated the DMARDs azathioprine, mycophenolate, or methotrexate. Compared with hydroxychloroquine initiators, DMARD initiators more often had a history of nephritis and had been given corticosteroids or infused medications in the 6 months prior to study enrollment.

Patients starting treatment with hydroxychloroquine had fewer infections requiring hospitalization than those initiating DMARDs (32 vs 57 per 1,000 person-years). The rate of serious infection overall was higher following DMARD initiation (HR 1.82, 95% CI 1.27-2.60), but the risk was no longer significant after adjustment for nephritis, previous infections, and exposure to corticosteroids (HR 1.30, 95% CI 0.86-1.95), the researchers reported.

Among the DMARD group, the infection rate was lowest for methotrexate, at 32 per 1,000 person-years, and highest for azathioprine, at 71 per 1,000.

In a fully adjusted model, azathioprine had a twofold greater risk for serious infection compared with methotrexate (HR 2.19, 95% CI 1.14-4.21), so counseling about infection risk may be warranted in patients initiating azathioprine, the authors said. The rate of infection with mycophenolate was 50 per 1,000 person years, with an adjusted hazard ratio of 1.39 (95% CI 0.65-2.96).

The researchers noted that the high rates of pneumonia in the SLE group compared with the general population (5.6% vs 1.5%) were a cause for concern. "Given the availability of immunizations for pneumonia and a considerable proportion of pneumonia infections in these patients with lupus, future work needs to build on past work showing low vaccination rates to further examine vaccine uptake and effectiveness in this population, and examine antibody response following vaccination," the team wrote.

Limitations of the study, the investigators said, included the possibility of disease misclassification and confounding by indication.

Source Reference: Simard JF, et al "Infection hospitalisation in systemic lupus in Sweden" Lupus Sci Med 2021; doi:10.1136/lupus-2021-000510.