ObjectiveWe investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE).MethodsUsing observational data from a U.S. multi‐center electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011‐2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab vs. each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury.ResultsAmong 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison, with mean age 45 years and 94% females. Compared to azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HRs 0.82 [95% CI 0.72‐0.92] and 0.69 [0.61‐0.78]), and hospitalization for infection (HRs 0.73 [95% CI 0.57‐0.94] and 0.56 [0.43‐0.71]). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86 [95% CI 0.76‐0.97]). There were no differences in traumatic injury risks across treatment groups.ConclusionBelimumab was associated with lower risks of serious infection than oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment.This article is protected by copyright. All rights reserved.image

Background: Evidence suggests that periodontal disease is associated with increased lung cancer risk, but whether periodontal pathogens are explanatory is unknown. We prospectively studied associations of pre-diagnostic circulating antibodies to oral bacteria and of periodontal bacteria in subgingival plaque with lung cancer. Methods: We included 4,263 cancer-free participants in the Atherosclerosis Risk in Communities study with previously measured serum IgG antibodies to 18 oral bacteria. In 1,287 participants for whom subgingival plaque was collected, counts for 8 periodontal bacteria were previously measured. Incident lung cancers (N=118) were ascertained through 2015 (median follow-up=17.5 years). We used Cox regression to estimate multivariable-adjusted associations, including for sums of antibodies to orange (C. rectus, F. nucleatum, P. intermedia, P. micra, P. nigrescens) and red (P. gingivalis, T. forsythensis, T. denticola) complex bacteria. Results: Orange complex bacteria antibodies were positively associated with lung cancer (per IQR HR=1.15, 95% CI 1.02-1.29), which was stronger in men (HR=1.27, 95% CI 1.08-1.49), and explained by P. intermedia and P. nigrescens (HR=1.15, 95% CI 1.04-1.26). Suggestive positive associations with lung cancer (N=40) were observed for F. nucleatum, A. actinomycetemcomitans, and P. gingivalis counts. Significant positive associations were found for count to antibody ratio for P. intermedia and P. gingivalis. Conclusions: We identified positive associations with lung cancer for oral bacteria, especially orange complex which are moderately pathogenic for periodontal disease. Impact: This prospective study supports the need for more research on periodontal bacteria in lung cancer etiology. If associations are supported, this may inform novel lung cancer prevention strategies.

Data regarding response to SARS-CoV-2 immunization in pediatric patients with predominantly antibody deficiency (PAD) is limited. We evaluated SARS-CoV-2 immunization response by anti-SARS-CoV-2-spike antibody level in 15 pediatric PAD patients. These data were compared to a published cohort of adult PAD patients (n=62) previously analyzed following SARS-CoV-2 immunization at our single center institution. We evaluated demographics, clinical characteristics, immunophenotype, infection history, and past medication use by chart review. Following a two-dose monovalent initial series SARS-CoV-2 immunization, mean anti-SARS-CoV-2-spike antibody levels were significantly higher in pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p<0.0001). Pediatric PAD patients with low class-switched memory B-cells, defined as <2% of total CD19+ B-cells, had significantly lower mean anti-SARS-CoV-2-spike antibody levels than those without (p=0.02). Following a third-dose monovalent SARS-CoV-2 immunization, the mean anti-SARS-CoV-2-spike antibody levels in pediatric PAD patients significantly increased (2,890.7 to 18,267.2 U/mL; p<0.0001). These data support Centers for Disease Control guidelines regarding three-part SARS-CoV-2 vaccine series, including in the pediatric PAD patient demographic.

Supplementary Method 1, Tables S1-S8, and Figures S1-S2 from Periodontal and Other Oral Bacteria and Risk of Lung Cancer in the Atherosclerosis Risk in Communities (ARIC) Study

Supplementary Method 1, Tables S1-S8, and Figures S1-S2 from Periodontal and Other Oral Bacteria and Risk of Lung Cancer in the Atherosclerosis Risk in Communities (ARIC) Study