Association of disease-modifying antirheumatic drug selection with hospitalised infection among youth with childhood-onset systemic lupus erythematosus.

Abstract

Objective: Youth with childhood-onset SLE (cSLE) have increased risk of serious infection. It is unknown how much of this risk is due to modifiable factors such as choice of immunosuppressant. We aimed to compare hospitalised infection rates in youth with cSLE on different disease-modifying antirheumatic drugs (DMARDs).

Methods: We included youth ≤18 years with cSLE treated from 2009 to 2022 at two centres. Clinical data were extracted from electronic health records and the Paediatric Health Information System. Hospitalised infection frequency was calculated over the first year of treatment in youth included in each DMARD exposure group, stratified by lupus nephritis (LN) status. Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) was used to compare infection rates across DMARD groups, adjusting for corticosteroid dose.

Results: Among 257 youths with cSLE, 5% had ≥1 hospitalised infection within 1 year of DMARD initiation. 8% of those with LN had ≥1 hospitalised infection compared with 2.5% without LN. In IPTW-adjusted models, children with LN treated with mycophenolate had lower risk of infection compared with those treated with cyclophosphamide (HR 0.12; 95% CI 0.019 to 0.88). Among those without LN, mycophenolate did not differ from azathioprine in infection risk (HR 1.67, 95% CI 0.56 to 4.99). Higher oral corticosteroid dosing (per 1 mg/day of prednisone) was associated with increased risk of infection (HR 1.1, 95% CI 1.05 to 1.15).

Conclusions: We observed higher hospitalised infection rates in children with cSLE and LN compared with those without LN. Among children with LN, those who received cyclophosphamide had more infections than those who received mycophenolate. Methotrexate was associated with lower infection rates than mycophenolate or azathioprine among youth without LN. Higher daily oral steroid dose was significantly associated with increased hospitalised infection risk in youth with non-renal SLE.